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| # | nctid | status | why_stop | prediction | phase | diseases | icdcodes | drugs | smiless | criteria |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | NCT01288573 | completed | 0.5353680849075317 | phase 1/phase 2 | ["ewing's sarcoma/soft tissue sarcoma", 'neuroblastoma', 'brain tumors'] | ["['C71.7', 'C71.9', 'C79.31', 'D33.0', 'D33.1', 'D33.2', 'D49.6']"] | ['plerixafor', 'plerixafor', 'plerixafor'] | ['C(N1CCCNCCNCCCNCC1)C1=CC=C(CN2CCCNCCNCCCNCC2)C=C1', 'C(N1CCCNCCNCCCNCC1)C1=CC=C(CN2CCCNCCNCCCNCC2)C=C1', 'C(N1CCCNCCNCCCNCC1)C1=CC=C(CN2CCCNCCNCCCNCC2)C=C1'] | Inclusion Criteria: - Age 2 to < 18 years during stage 1 and 1 to < 18 years during stage 2 - Ewing's sarcoma, soft tissue sarcoma, lymphoma, neuroblastoma, brain tumors or other malignancy (excluding any form of leukemia) requiring treatment with high dose chemotherapy and autologous transplant as rescue therapy - Eligible for autologous transplantation - Recovered from all acute significant toxic effects of prior chemotherapy - Adequate performance status (for patients ≥16 years of age, defined as Karnofsky score >60 and for patients <16 years of age, defined as Lansky score >60) - Absolute neutrophil count >0.75 × 10^9/L - Platelet count >50 × 10^9/L - Calculated creatinine clearance (using the Schwartz method): during study Stage 1, >80 mL/min/1.73m^2 and during study Stage 2, >60 mL/min/1.73m^2 - Aspartate aminotransferase(AST)/serum glutamic oxaloacetic transaminase(SGOT), alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase (SGPT) and total bilirubin <3 × upper limit of normal - The patient and/or their parent/legal guardian is willing and able to provide signed informed consent - Patients who are sexually active must be willing to abstain from sexual intercourse or agree to use an approved form of contraception while receiving plerixafor and/or standard mobilization treatment and for at least 3 months following any plerixafor treatment Exclusion Criteria: - Any form of leukemia - A co-morbid condition which, in the view of the Investigator, renders the patient at high-risk from treatment complications - Previous stem cell transplantation - Persistent high percentage marrow involvement prior to mobilization will be prohibited. - On-going toxicities (excluding alopecia) Grade ≥2 resulting from prior chemotherapy - Acute infection - Fever (temperature >38.5°C) - if fever is between 37°C and 38.5°C, infection must be excluded as a cause - Known HIV seropositivity, AIDS, hepatitis C or active hepatitis B infections - Positive pregnancy test in post pubertal girls - History of clinically significant cardiac abnormality or arrhythmia - Use of an investigational drug which is not approved in any indication either in adults or pediatrics within 2 weeks prior to the first dose of G-CSF to be administered as part of the patient's planned standard mobilization regimen, and/or during the study up until engraftment of the transplant. If patients are on investigational drugs as part of their anti-cancer regimen, this should be discussed with the Sponsor before screening. Drugs approved for other indications that are being used in a manner considered standard of care for this transplant procedure are allowed - The patient (and/or their parent/legal guardian), in the opinion of the Investigator, is unable to adhere to the requirements of the study | |
| 2 | NCT01558674 | terminated | lack of efficacy | 0.5437843799591064 | phase 1 | ['renal impairment', 'heart failure'] | ["['M10.38', 'M10.30', 'M10.311', 'M10.312', 'M10.319', 'M10.321', 'M10.322']", "['I50.814', 'I09.81', 'I50.82', 'I50.89', 'I50.9', 'T86.22', 'I11.0']"] | ['mk-7145', 'furosemide', 'torsemide'] | ['CC1=C2COC(=O)C2=CC=C1[C@@H](O)CN1CCN(C[C@H](O)C2=C(C)C3=C(C=C2)C(=O)OC3)CC1', 'CCOC(=O)OC[C@H]1O[C@@H](OC2=NN(C(C)C)C(C)=C2CC2=CC=C(OC(C)C)C=C2)[C@H](O)[C@@H](O)[C@@H]1O', 'CC(C)NC(=O)NS(=O)(=O)C1=C(NC2=CC=CC(C)=C2)C=CN=C1'] | Inclusion Criteria: Parts I and II - If female, must be of non-child bearing potential or, if of child-bearing potential agrees to use at least 2 acceptable contraceptive measures - Body Mass Index (BMI) >=17.5 and <=38 kg/m^2 - No present history of clinically significant uncontrolled arrhythmias on electrocardiogram (ECG) - Nonsmoker or a light smoker consuming up to an average of 20 cigarettes (or equivalent tobacco product) per day. Part I Only - Estimated creatinine clearance of ≤45 mL/min. Part II Only - Class II or III heart failure as specified by the New York Heart Association (NYHA) functional classification for heart failure with NT-proBNP >=1000 pg/mL on clinically optimized therapy with a stable dose (for at least 2 weeks) of furosemide or torsemide - Estimated creatinine clearance of ≤45 mL/min Exclusion Criteria: Parts I and II - Mentally or legally institutionalized and/or incapacitated, has significant emotional problems or has a history of a clinically significant psychiatric disorder over the last 5 years. This includes any mood disorder requiring concomitant use of lithium - Diagnosed with acute coronary syndrome or acute cardiovascular (CV) event, or has been hospitalized for HF exacerbation within less than 3 months of study entry - Unstable angina pectoris - Diabetes requiring high dose peroxisome proliferator-activated receptor (PPAR) antagonist (e.g. >30 mg of pioglitazone) or unstable insulin use - Infectious disease requiring concomitant use of aminoglycosides - Low plasma potassium (hypokalemia) - Recent (within 6 months) history of stroke, uncontrolled seizures, or uncontrolled major neurological disorder - Urinary retention, hydronephrosis or hydroureter - Active nephrocalcinosis, nephrolithiasis, or hypercalciuria - Functional disability that can interfere with rising from a semi-recumbent position to the standing position - History of malignant neoplastic disease - Unable to refrain from the use of medication, including prescription and non-prescription drugs such as high-dose aspirin (≥325 mg/day), non-steroidal anti-inflammatory drugs (NSAIDs), human immunodeficiency virus (HIV) protease inhibitors (ritonavir, indinavir, nelfinavir), macrolide antibiotics (erythromycin, telithromycin, clarithromycin), chloramphenicol, azole antifungals (fluconazole, ketoconazole, itraconazole, nefazodone, aprepitant, verapamil, diltiazem, etc.), anticonvulsants and mood stabilizers (e.g., phenytoin, carbamazepine, oxcarbazepine), barbiturates (phenobarbital), HIV non-nucleoside reverse transcriptase inhibitors (efavirenz, nevirapine, etravirine), rifampicin, modafinil, St John's wort, cyproterone (antiandrogen, progestin), etc. beginning approximately 2 weeks (or 5 half-lives), prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods) until the poststudy visit - Consumes excessive amounts of alcohol, defined as greater than 5 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day - Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day - Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks - Regular user of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 6 months |
| 3 | NCT01575782 | terminated | poor accrual | 0.37431642413139343 | phase 1 | ['small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['chloroquine'] | ['CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1'] | Inclusion Criteria: - Histologically or cytologically confirmed stage I-III small cell lung cancer, excluding malignant pleural/pericardial effusion. - At least one measurable disease site, defined as lesion of ≥ 1 cm unidimensionally on CT-scan - WHO performance status 0-2 - Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l. - Adequate renal function: calculated creatinine clearance at least 60 ml/min - Adequate hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution (in case of liver metastases ≤ 5 x ULN for the institution) - No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC. - Lung function: FEV1 at least 30 % and DLCO at least 30 % of the age predicted value - No history of prior chest radiotherapy - Life expectancy more than 6 months - Willing and able to comply with the study prescriptions - 18 years or older - Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study - Ability to give and having given written informed consent before patient registration - No mixed pathology, e.g. non-small cell plus small cell cancer - No recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction) - No history of cardiac arrythmia (multifocal premature ventricular contractions, uncontrolled atrial fibrillation, bigeminy, trigeminy, ventricular tachycardia) which is symptomatic and requiring treatment (CTC AE 3.0), or asymptomatic sustained ventricular tachycardia. Asymptomatic atrial fibrillation controlled on medication is allowed. - No cardiac conduction disturbances or medication potentially causing them: - QTc interval prolongation with other medications that required discontinuation of the treatment - Congenital long QT-syndrome or unexplained sudden death of first degree relative under 40 years of age - QT interval > 480 msec (note: when this is the case on screening ECG, the ECG may be repeated twice. If the average QT-interval of these 3 measurements remains below 480 msec, patient is eligible) - Patients on medication potentially prolongating the QT-interval are excluded if the QT-interval is > 460 msec (Appendix, table 2). - Medication that might cause QT-prolongation or Torsades de pointes tachycardia is not allowed (Appendix, Table 1). Drugs with a risk of prolongating the QT-interval that cannot be discontinued are allowed, however, under close monitoring by the treating physician (Appendix, table 2). - Complete left bundle branch block - No uncontrolled infectious disease - No other active malignancy - No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy) in previous 4 weeks - No treatment with investigational drugs in 4 weeks prior to or during this study - No chronic systemic immune therapy - No known G6PD deficiency - Patients must not have psoriasis or porphyria. - No known hypersensitivity to 4-aminoquinoline compound. - Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use. - No known prior hypersensitivity to cisplatin, etoposide or chloroquine or any of their components. Exclusion Criteria: - The opposite of the above |
| 4 | NCT01609816 | terminated | low accrual. no analyses were performed | 0.6395378112792969 | phase 1 | ["non-hodgkin's lymphoma", 'multiple', 'mycosis fungoides', "hodgkin's lymphoma", 'multiple myeloma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['G35', 'M15.3', 'M67.49', 'M89.09', 'M89.59', 'M94.29', 'Q78.6']", "['C84.07', 'C84.00', 'C84.02', 'C84.06', 'C84.03', 'C84.08', 'C84.09']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C90.01', 'C90.02', 'C90.00']"] | ['dasatinib'] | ['CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1'] | Inclusion Criteria: - Recipients of first ASCT for the treatment of hematologic malignancies (multiple myeloma, Hodgkin's and non Hodgkin's lymphoma) - Patients must be between 100 to 180 days after ASCT - Dasatinib use prior to ASCT is allowed - Performance status >= 60% - Presence of LGL clone prior to enrollment will not be an exclusion criterion if the LGL clone is < 25% of T cell population - Total bilirubin < 2.0 times the institutional upper limit of normal (ULN) - Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) =< 2.5 times the institutional ULN - Serum creatinine < 1.5 times the institutional ULN - Hemoglobin >= 8 g/dL - Absolute neutrophil counts >= 1,500 cells per uL - Platelets >= 100,000 per uL - Patient should be able to provide signed written informed consent; before any study procedures are performed, subjects will have the details of the study described to them, and they will be given a written informed consent document to read; then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of study personnel; written consent will include a Health Insurance Portability and Accountability Act (HIPAA) form according to institutional guidelines - Patient should be able to take oral medication (dasatinib must be swallowed whole) Exclusion Criteria: - Patients who have evidence of disease progression before day 100 after ASCT - Sex and reproductive status: - Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 4 weeks after the last dose of study drug - Women who are pregnant or breastfeeding - Women with a positive pregnancy test - Sexually active fertile men not using effective birth control if their partners are WOCBP - Medical history and concurrent diseases: - No malignancy (other than the one treated in this study) which required radiotherapy or systemic treatment within the past 5 years - Concurrent medical condition which may increase the risk of toxicity, including: - Pleural or pericardial effusion of any grade at the time of screening for study - Cardiac symptoms; any of the following should be considered for exclusion: - Uncontrolled angina, congestive heart failure or myocardial infarction (MI) (within 6 months) - Diagnosed congenital long QT syndrome - Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) - Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 450 msec) - History of significant bleeding disorder unrelated to cancer, including: - Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)* Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) - Ongoing or recent (=< 3 months) significant gastrointestinal bleeding - Any previous history of >= grade 3 toxicity to dasatinib - Prohibited treatments and or therapies - Category I drugs that are generally accepted to have a risk of causing torsades de pointes including: (patients must discontinue drug 7 days prior to starting dasatinib): - Quinidine, procainamide, disopyramide - Amiodarone, sotalol, ibutilide, dofetilide - Erythromycin, clarithromycin - Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide - Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine - Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy (discontinue St. Johns Wort at least 5 days before starting dasatinib) - Patient agrees that intravenous (IV) bisphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia - Other exclusion criteria: - Prisoners or subjects who are involuntarily incarcerated - Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness |
| 5 | NCT01657760 | completed | 0.7224372625350952 | phase 1 | ['alcohol dependence'] | ["['F10.20', 'F10.24', 'F10.27', 'F10.280', 'F10.281', 'F10.282', 'F10.288']"] | ['citalopram'] | ['CN(C)CCCC1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1'] | Inclusion Criteria: Must be U.S. Veteran Alcohol Dependence: - Age between 21 and 55; - Meeting DSM-IV diagnostic criteria for alcohol dependence; - Report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment, and - Must have had at least 2 days of heavy drinking (at least 5 drinks/day for men, 4 drinks/day for women) in the last 30 days Healthy Control: - Age between 21 and 55; - No Axis I DSM-IV diagnosis (except for nicotine dependence); - Report drinking less than 10 drinks weekly over the past 90 days prior to study entry by Timeline Followback Method (TLFB). Exclusion Criteria: Exclusion criteria for Alcohol Dependence: - Current treatment for alcohol problems or a history of treatment in the 30 days before enrollment or are treatment seeking; - A current (last 12 months) DSM-IV diagnosis of dependence on any psychoactive substances other than alcohol and nicotine. Exclusion criteria for Healthy Controls: - Any history of treatment for alcohol or other substance use disorders; - Any history of DSM-IV diagnosis of dependence on any psychoactive substances other than nicotine; - Any history of DSM-IV diagnosis of Axis I mental illness. Exclusion criteria for all subjects: - A current (last 12 months) DSM-IV diagnosis of schizophrenia, bipolar disorder, other psychotic disorder, eating disorder, panic disorder with or without agoraphobia; - Current use of psychoactive drugs, other than occasional marijuana use (< 3 uses per week), as determined by a positive urine screen for narcotics, amphetamines, or sedative hypnotics; - Serious alcohol withdrawal symptoms as indicated by a score > 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA); - Clinically significant physical abnormalities as indicated by physical examination, hematological laboratory assay, or urinalysis, defined as: hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, alanine transaminase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 x the upper limit of normal; - A screening ECG that demonstrates anything other than normal sinus rhythm, normal conduction, and no clinically significant arrhythmias; - History of epilepsy, seizures, or severe head trauma; - History of alcohol intoxication delirium, alcohol withdrawal delirium or seizure, alcohol-induced persisting dementia, or alcohol-induced psychosis; - Treatment with any of the following medications within the last 30 days prior to randomization: antidepressants, anti-convulsants, hypnotics, antipsychotics, psychomotor stimulants, or anti-anxiety agents; - Previous treatment with citalopram discontinued due to an adverse event; - Pregnancy, nursing, or refusal to use reliable barrier method of birth control, if female; - Presence of metal fragments, pacemaker, or other ferromagnetic material which would prevent safe completion of an MRI scan; - Recent history of radiation exposure which would make exposure to radiation from serial PET scans contraindicated; - Non-zero breath-alcohol level on screening. We will exclude participants who present to study appointments intoxicated, as active alcohol intoxication may interact unpredictably with citalopram and produce unreliable results in assessments of mood or alcohol craving (e.g. Ray and Hutchison, 2007; Ray et al., 2011; see preliminary data C.2. above); - Resting vital signs on any study visit outside of acceptable parameters: Pulse of 50-105 bpm, Blood pressures of 90-160 mm Hg systolic, 55-100 mm Hg diastolic; - Any indication of suicidal ideation (i.e. as assessed by question 9 on the Beck Depression Inventory-II [BDI-II]), or elevated index of depressive symptoms, as evidenced by BDI-II score of 20; - Presence in the body of a metal device (e.g., pacemaker, infusion pump, aneurysm clip, metal prosthesis or plate) that could either interfere with the acquisition of the MRI scan of the brain or for whom the MRI scan would pose a potential risk will be excluded. - Radiation exposure: Participation in any other research study involving exposure to ionizing radiation in the past year if the total cumulative exposure from the past research studies and the current research study would exceed the limits described by the FDA in 21 CFR 361.1. Specifically, the total cumulative dose to the whole body, active blood-forming organs, lens of the eye, and gonads must remain below 5 rems, and the cumulated dose to all other organs must remain below 15 rems over the last year. | |
| 6 | NCT01746784 | completed | 0.550201416015625 | phase 1 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['n6022', 'normal saline'] | ['CC1=CC(=CC=C1N1C(CCC(O)=O)=CC=C1C1=CC=C(C=C1)N1C=CN=C1)C(N)=O', 'O'] | Inclusion Criteria: - Homozygous for F508del-CFTR gene - Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis - Body weight ≥ 40 kg - FEV1 ≥ 40% predicted - Oxygen saturation ≥ 90% breathing ambient air - Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments - Negative pregnancy test for women of child bearing potential - Sexually active subjects of child bearing potential willing to follow contraception requirements Exclusion Criteria: - Previous enrollment in another cohort for this study. - Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day 1. - Any change in chronic therapies for CF lung disease within 4 weeks of Study Day 1. - Blood hemoglobin <10 g/dL at screening. - Serum albumin <2.5 g/dL at screening. - Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening. - History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening. - History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias. - History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec). - History of solid organ or hematological transplantation. - Intranasal medication changes within 14 days prior to Study Day 1 - Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen. - Concomitant use of any inhibitors or inducers of CYP3A4. | |
| 7 | NCT01799161 | withdrawn | insufficient funding | 0.39498913288116455 | phase 1 | ['non-small cell lung cancer', 'non-small-cell lung carcinoma', 'lung cancer', 'nsclc'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['D02.20', 'D02.21', 'D02.22']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['theophylline'] | ['CN1C2=C(NC=N2)C(=O)N(C)C1=O'] | Inclusion Criteria: - Histologically confirmed NSCLC (squamous, adeno-, large cell anaplastic, bronchoalveolar, and non-small cell carcinoma NOS): stage IIIB with malignant pleural effusion, stage IV, or recurrent disease. - At least one site of measurable disease. - Brain metastasis if present and treated must be stable by CT scan or MRI for at least 4 weeks after treatment. - Patient must have received and failed at least one line of palliative therapy (chemotherapy or biological therapy) - Age >= 18 years. - ECOG performance status 0-2. - Life expectancy >= 3 months. - Laboratory parameters - Hemoglobin levels >= 10.0 (transfusions allowed if necessary). - ANC >= 1,500. - Platelets >= 100k. - Creatinine clearance >= 50 ml/min. - Total and direct bilirubin: < 3.0 x upper institution limit for normal. - Liver function tests: AST, ALT, and AlkP < 3.0 x upper institution limit for normal. - Signed informed consent. Exclusion Criteria: - Active or symptomatic cardiac disease such as congestive heart failure, angina pectoris or recent myocardial infarction. Patients with history of these conditions who are stable taking cardiac medications will also be excluded. - Pregnant or lactating women (negative test for pregnancy is required of women of childbearing potential). - Known HIV infection. - Uncontrolled or untreated brain or spinal cord metastases. - Active infection. - Concomitant steroid or other immunosuppressive therapy. - Other active malignancies present within the past three years, except for basal and/or squamous cell carcinoma(s) or in situ cervical cancer. - Meningeal carcinomatosis. - Chemotherapy, radiation therapy, or other anti-tumor therapy during the last three weeks. - Immune deficiency syndromes, including the following: rheumatoid arthritis, systemic lupus erythematousus, Sjogren's disease, sarcoidosis, vasculitis, polymyositis, glomerulonephritis. - Compromised lung function: - FeV1 < 30% of the predicted value, or - DLCO < 30% of the predicted value, or - PCO2 > 45 mmHg. |
| 8 | NCT01803399 | withdrawn | emerging gsk1322322 pre-clinical data id'd potentially reactive metabolites previously not seen that changed the risk: benefit profile and led to a termination | 0.5098913311958313 | phase 1 | ['infections, bacterial'] | ["['A49.9', 'A04.9', 'A04.8', 'A49.8']"] | ['gsk1322322 1200 mg', 'gsk1322322 3000 mg', 'placebo', 'moxifloxacin'] | ['CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1', 'CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C'] | Inclusion Criteria: - Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures - Male or female (of non childbearing potential) between 18 and 65 years of age inclusive, at the time of signing the informed consent - A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] >40 milli international units [mIU]/millilitre [mL] and estradiol <40 picograms [pg]/mL or <147 picomole [pmol]/litre [L] is confirmatory) - Male subjects with female partners of child-bearing potential must agree to use one of the following contraception methods from the time of the first dose of study medication until the final follow up visit - Condom plus partner use of a highly effective contraceptive; Abstinence, defined as sexual inactivity consistent with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Body weight >=50 kilograms (kg) for men and >=45 kg for women and body mass index (BMI) within the range 18.5-31.0 kg/(square metre) m^2 (inclusive) - Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5 x Upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening and check-in (repeat allowed at check-in only) - Serum Potassium, Calcium and Magnesium lab parameters within normal limits at screening and check-in (repeat allowed at check-in only) - QTcB <450 milliseconds (msec) at screening and check-in - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Exclusion Criteria: - History/evidence of any arrhythmia (for example, first, second or third degree heart block, atrial fibrillation, supraventricular tachycardia, sinus bradycardia, junctional rhythm) or clinically significant cardiac disease or procedure(mitral valve regurgitation, heart murmur, angina/ischemia, congenital heart abnormalities, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PCTA). Personal or family history of long QT syndrome - Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs. Subjects with a history of cholecystectomy, inflammatory bowel disease or pancreatitis. Subjects with active peptic ulcer disease or a history of upper gastrointestinal bleeding - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) - History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits - A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody result, or a positive test for Human Immunodeficiency Virus (HIV) antibody within 3 months of screening - A positive pre-study drug/alcohol screen - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) - Exposure to more than four new chemical entities within 12 months prior to the first dosing day - Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety due to potential drug interaction - History of sensitivity to any of the study medications, quinolone antibiotics, (including moxifloxacin), or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period - Pregnant females as determined by positive (serum or urine) Human chorionic gonadotropin (hCG) test at screening or prior to dosing - Lactating females - Unwillingness or inability to follow the procedures outlined in the protocol - Subject is mentally or legally incapacitated - History of sensitivity to heparin or heparin-induced thrombocytopenia - Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening - Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice (and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices) from 7 days prior to the first dose of study medication - Exclusion criteria for screening Holter and ECG (a single repeat is allowed for eligibility determination): Heart rate <45 and >100 beats per minute (bpm) for males or <50 and >100 bpm for females; PR Interval <120 and >220 msec; QRS duration <70 and >120 msec; QTc interval (Bazett) >=450 msec (Note: The waveforms must enable the QT interval to be clearly defined); Q wave >30 msec - Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization) - Any conduction abnormality (including but not specific to left or right bundle branch block, Atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson White [WPW] syndrome), sinus pauses>3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject |
| 9 | NCT01812616 | completed | 0.6066207885742188 | phase 1/phase 2 | ['cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['sativex', 'placebo'] | ['[H][C@@]12C=C(C)CC[C@@]1([H])C(C)(C)OC1=C2C(O)=CC(CCCCC)=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Patient is willing and able to give informed consent for participation in the study. - Patient is aged 18 years or above. - Histopathologically confirmed diagnosis of grade four Glioblastoma Multiforme as per World Health Organisation classification. - Evidence of patients first tumour progression (as determined by Revised Assessment in Neuro-Oncology) following radiation and first line chemotherapy with Temozolomide. - If taking steroids, then the dose must be stable or decreasing. - Karnofsky performance scale of 60% or greater. - Patient is able (in the investigators opinion) and willing to comply with all study requirements. - Patient is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries. - Patient is willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study. Exclusion Criteria: - Patients with Glioblastoma Multiforme secondary to low-grade glioma or anaplastic glioma (anaplastic astrocytoma or anaplastic oligodendroglioma). - Patients currently receiving treatment for recurrent Glioblastoma Multiforme. - Less than a four week interval since prior chemotherapy. - Less than a 12 week interval since prior radiotherapy unless there is either: a) histopathology confirmation of recurrent tumour, or b) new enhancement on Magnetic Resonance Imaging outside of the radiotherapy treatment field. - Presence of extra-cranial metastatic disease. - Any surgery, including intracranial biopsy (not including minor diagnostic procedures such as lymph node biopsy) within two weeks of baseline disease assessments; or not fully recovered from any side effects of previous procedures. - Any history of a different malignancy unless the patient has remained disease-free for at least three years and are at low risk for recurrence of that malignancy (cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin are exempt from this criterion if treatment has occurred). - Have previously received first line chemotherapy other than Temozolomide. - Presents with Leptomeningeal dissemination. - Have previously received stereotactic radiotherapy, convection enhanced delivery or brachytherapy (as gliosis/scarring from these modalities may limit delivery). - The patient is currently using or has used cannabis or cannabinoid based medications within 30 days of study entry and is unwilling to abstain for the duration of the study. - Any known or suspected history of a substance abuse/dependence disorder, current heavy alcohol consumption (>60g of pure alcohol per day for men, >40 g of pure alcohol per day for women), current use of an illicit drug or current non prescribed use of any prescription drug. - Any history or immediate family history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition. - Has experienced myocardial infarction or clinically significant dysfunction within the last 12 months or has a cardiac disorder that, in the opinion of the investigator would put the patient at risk of clinically significant arrhythmia or myocardial infarction. - Has grade 3 or above toxicity by Common Terminology Criteria for Adverse Events criteria. - Female patients of child bearing potential and male patients whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (however a male condom should not be used in conjunction with a female condom). - Female patients who are pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter. - Patient who have received an Investigational Medicinal Product within the four weeks prior to the screening visit. - Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study, or may influence the result of the study, or the patient's ability to participate in the study. - Travel outside the country of residence planned during the study. - Patients previously enrolled into this study and received either Investigational Medicinal Product or Dose-Intense Temozolomide. - Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product. - Any known allergy to or other intolerability to Temozolomide. - Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study. - Unwilling to abstain from donation of blood during the study. | |
| 10 | NCT01836289 | withdrawn | too difficult to recruit given new crohn's medications approved | 0.49471643567085266 | phase 1/phase 2 | ["crohn's disease", 'crohn disease'] | ["['K50.90', 'K50.913', 'K50.914', 'K50.911', 'K50.912', 'K50.918', 'K50.919']", "['K50.90', 'K50.913', 'K50.914', 'K50.911', 'K50.912', 'K50.918', 'K50.919']"] | ['high-dose cyclophosphamide'] | ['[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CSC(N)=N1)C(O)=O'] | Inclusion Criteria: - ≥ 18 years of age, males and females will be eligible - Moderate to severe Crohn's Disease (CD) with CDAI > 220, in addition to evidence of ulceration on ileocolonoscopy or active disease on small bowel imaging (in patients with an ostomy, CDAI criteria do not apply) - Disease progression (primary or secondary non-responder, or reaction to) to at least one anti-tumor necrosis factor (TNF) agent (infliximab, adalimumab, certolizumab pegol), and additionally had disease progression despite one of the following immunosuppressant drugs: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine, natalizumab, vedolizumab - Willingness to participate in a clinical trial - Approval by Enrollment Panel, who will collectively decide on the appropriateness of possible study study participants Exclusion Criteria: - Pregnant or nursing women - Sexually active men and women who do not agree to use effective means of birth control during treatment period - Evidence of primarily fibrostenosing disease without active inflammatory disease on disease staging - Co-morbid conditions including cardiac disease with an ejection fraction of < 45%, chronic renal failure with serum creatinine > 2.0, liver disease with total bilirubin > 2.0, (excluding hyperbilirubinemia secondary to Gilbert's disease) or transaminitis > 3x upper limit of normal. - History of serious allergic reaction to cyclophosphamide - History of malignancy in the last 5 years (excluding non-melanomatous skin cancers) - Patients who are pre-terminal - Toxic megacolon - Active infection - White blood cell count < 3000 cells/ul, platelets < 100K / ul, hemoglobin < 10.0 g/dL - Any use of thiopurines, methotrexate or anti-TNF agents in the previous four weeks prior to treatment |
| 11 | NCT01838200 | terminated | slow recruitment due to changes in standard of care | 0.47773319482803345 | phase 1 | ['metastatic melanoma'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['ipilimumab', 'isoniazid'] | ['COC1=CC=CC=C1OCC(O)CO', 'NNC(=O)C1=CC=NC=C1'] | Inclusion Criteria: 1. Histologically confirmed stage III (unresectable) or stage IV melanoma. 2. Minimum 1 metastatic lesion, cutaneous or subcutaneous, but ideally 3 or more lesions, to accommodate intralesional injection (1 lesion), accessibility for biopsy (1 lesion), and evaluability for response by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (1 lesion) and modified RECIST (immune-related response criteria [irRC]). 3. Performance status of Eastern Cooperative Oncology Group 0-1. 4. Within the last 2 weeks prior to study Day 1, vital laboratory parameters must have been within normal ranges, except for the following laboratory parameters, which must have been within the ranges specified: - Hemoglobin: ≥ 100 g/L - Platelets: ≥ 100 x 10^9/L - International normalized ratio: ≤ 2.0 - Creatinine: ≤ 120 µmol/L - Bilirubin: ≤ 30 µmol/L - Estimated glomerular filtration rate: > 0.75 x lower limit of normal - Aspartate and alanine aminotransferase: ≤ 2.0 x upper limit of normal - Albumin: > 28 g/L - Neutrophils: > 1.5 x 10^9/L - Lymphocytes: > 0.5 x 10^9/L 5. Estimated life expectancy of at least 4 to 6 months. Because of the slow onset of action of ipilimumab and the protocol requirement for a 5-week delay post-BCG, patients with rapidly progressive disease may not have been suitable for the protocol. 6. Full recovery from surgery. A minimum of 2 weeks should have elapsed since the most recent surgery. 7. Men and women ≥ 18 years of age. 8. Able and willing to give written informed consent. Exclusion Criteria: 1. Active cerebral metastases unless stable after radiation for at least 1 month and not requiring corticosteroid treatment for 30 days prior to enrollment. 2. Other known malignancy within 3 years prior to entry into the study, except for treated non-melanoma skin cancer and cervical carcinoma in situ. 3. History of tuberculosis. 4. History of hypersensitivity to BCG. 5. Any contraindication to the use of isoniazid. 6. Generalized skin disease. 7. Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, were excluded from this study, as were patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis). Exceptions: vitiligo, type I diabetes, pernicious anemia (treated). 8. Any underlying medical or psychiatric condition, which in the opinion of the Investigator would have made the administration of ipilimumab hazardous or obscured the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea. 9. Prior immunotherapy or systemic adjuvant therapy for melanoma following most recent relapse and/or resection of melanoma. 10. Prior treatment with a cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor. 11. Concomitant therapy with any of the following: interleukin 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids. 12. Known human immunodeficiency virus positivity, Hepatitis B or Hepatitis C. 13. Chemotherapy or radiation therapy within the preceding 4 weeks (6 weeks for nitrosourea drugs). 14. Lack of availability for immunological and clinical follow-up assessments. 15. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing. 16. Mental impairment that may have compromised the ability to give informed consent and to comply with the requirements of the study. 17. Women who were pregnant (positive pregnancy test at baseline), or breastfeeding. 18. Men and women unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug. 19. Prisoners or patients who were compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness. |
| 12 | NCT01849276 | terminated | slow accrual | 0.5334560871124268 | phase 1 | ['adult acute megakaryoblastic leukemia (m7)', 'adult acute minimally differentiated myeloid leukemia (m0)', 'adult acute monoblastic leukemia (m5a)', 'adult acute monocytic leukemia (m5b)', 'adult acute myeloblastic leukemia with maturation (m2)', 'adult acute myeloblastic leukemia without maturation (m1)', 'adult acute myeloid leukemia with 11q23 (mll) abnormalities', 'adult acute myeloid leukemia with del(5q)', 'adult acute myeloid leukemia with inv(16)(p13;q22)', 'adult acute myeloid leukemia with t(16;16)(p13;q22)', 'adult acute myeloid leukemia with t(8;21)(q22;q22)', 'adult acute myelomonocytic leukemia (m4)', 'adult erythroleukemia (m6a)', 'adult pure erythroid leukemia (m6b)', 'blastic phase chronic myelogenous leukemia', 'recurrent adult acute myeloid leukemia', 'untreated adult acute myeloid leukemia'] | ["['C94.21', 'C94.22', 'C94.20']", "['C7A.1']", "['C93.01', 'C93.02', 'C93.00']", "['C93.Z1', 'C93.Z2', 'C93.91', 'C93.92', 'C93.01', 'C93.02', 'C93.Z0']", "['C92.01', 'C92.02', 'C92.00']", "['C92.01', 'C92.02', 'C92.00']", "['R19.5', 'H35.09', 'M26.50', 'M26.59', 'Q99.8', 'R06.89', 'R06.9']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C92.51', 'C92.52', 'C93.11', 'C93.12', 'C93.31', 'C93.32', 'C92.50']", "['C94.01', 'C94.02', 'C94.00']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']"] | ['metformin hydrochloride', 'cytarabine'] | ['CN(C)C(=N)NC(N)=N', 'ClCCN(CCCl)P1(=O)NCCCO1'] | Inclusion Criteria: - Patients with relapsed/refractory disease must have morphologic proof (from bone marrow aspirate, smears or touch preps of bone marrow biopsy) of AML with >= 10% blasts within two weeks (14 days) prior to initiation of therapy - All immunophenotype and cytogenetic/molecular groups are eligible for participation except for acute promyelocytic leukemia (APL) (as proven by the presence of promyelocytic leukemia/retinoic acid receptor alpha [PML-RARα]) - Patients must demonstrate one of the following: - Relapse after first complete remission - Refractory to conventional induction chemotherapy (failure to respond to 1 or more cycles of daunorubicin and cytarabine) or to re-induction - Patients with previously untreated AML are candidates if they are unable to receive anthracyclines, and have documented AML with >= 20% blasts within one week prior to enrollment - Patients with chronic myelogenous leukemia (CML) in myeloid blast crisis are eligible if their disease has failed to respond, and/or they are intolerant, to the available tyrosine kinase inhibitors (TKIs) - Serum total and direct bilirubin =< upper limit of normal (ULN) - Serum creatinine < 1.4 mg/dl in females and < 1.5 mg/dl in males, and creatinine clearance > 60 mL/min - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamic pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< ULN - Bicarbonate within the normal range of the hospital lab (24-32 mmol/L) - Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 - Females of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception while on study - Childbearing potential is defined as any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: - Has NOT undergone a hysterectomy or bilateral oophorectomy; OR - Has NOT been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months) - Patients with a history of central nervous system (CNS) leukemia are eligible if they are not symptomatic from current CNS involvement - If there is CNS involvement that is known prior to enrollment or identified subsequently, it will be treated accordingly - Patients may have received therapy for other malignancies, as long as they have completed therapy at least 6 months prior to study entry and be deemed to have a life expectancy of at least 2 years with regard to that malignancy - All patients must have given signed, informed consent prior to registration on study Exclusion Criteria: - Patients who have received chemotherapy or radiotherapy within 4 weeks prior to enrollment are NOT eligible for participation - The exception to this is patients who are refractory to conventional initial induction chemotherapy (=< 2 courses) or to first radiation (1 course); patients must have morphologic proof (from bone marrow aspirate, smears, or touch preps of marrow biopsy) of AML with > 10% blasts within 2 weeks prior to initiation of study therapy; the last dose of cytotoxic therapy (NOT including hydrea, which is allowed) must have been given >= 14 days prior to initiation of study therapy - Patients with a history of diabetes mellitus (DM) treated with metformin are NOT eligible for participation - Patients who are pregnant or breast feeding are NOT eligible for participation due to the lack of knowledge regarding the effects of the drugs on the fetus and during breast feeding - Patients with any intercurrent organ damage or medical problems that would prohibit therapy are NOT eligible for participation - Patients with any active, uncontrolled infection are NOT eligible for participation - Patients who are receiving therapy for another active malignancy are NOT eligible for participation - The exception to this is squamous cell carcinoma or basal cell carcinoma of the skin |
| 13 | NCT01852890 | active, not recruiting | 0.359515517950058 | phase 1 | ['pancreatic neoplasms'] | ["['C25.3']"] | ['ascorbate', 'gemcitabine'] | ['[H][C@@]1(OC(=O)C(O)=C1O)[C@@H](O)CO', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Patients must have histologically or cytologically diagnosed pancreatic adenocarcinoma. Documentation of disease extent by CT scan is required. Radiologically measurable disease is not required. - Age ≥ 18 years - ECOG performance status 0, 1, or 2 (Karnofsky > 50%). - A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below: - Absolute neutrophil count (ANC) ≥ 1500 cells per mm3 - Platelets ≥ 100,000 per mm3 - Leukocytes ≥ 3,000 per mm3 - Serum blood chemistries within 21 days of radiation fraction 1, as defined below: - Creatinine ≤ 1.5 x UIHC upper limit of normal or creatinine clearance of at least 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal. - Total bilirubin ≤ 2 x UIHC upper limit of normal - ALT ≤ 2.5 times the UIHC upper limit of normal - AST ≤ 2.5 times the UIHC upper limit of normal - PT/INR within normal limits (UIHC) - Tolerate one test dose (15g) of ascorbate. - Not pregnant. - Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: - G6PD (glucose-6-phosphate dehydrogenase) deficiency. - Prior abdominal radiotherapy that would result in overlap of fields. The treating radiation oncologist should review prior RT fields as available. - Adjuvant therapy (including radiation therapy) within 2 calendar weeks. Toxicities from prior therapy for the malignancy should resolve to grade 1 or less. - Patients actively receiving insulin are excluded. - Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs. - Second malignancy other than non-melanoma skin cancers within the past 5 years. - Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable). - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members. - Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are well documented. - Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 1 study. | |
| 14 | NCT01889420 | terminated | low accrual | 0.6886731386184692 | phase 1 | ['multiple myeloma in relapse'] | ["['C90.02']"] | ['combination therapy'] | ['CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC=CC=C2C[C@H]1C(O)=O'] | Inclusion Criteria: Age > 18 years Relapsed or progressive multiple myeloma (MM) (Progressive Disease), defined as a 25% increase from the lowest response value in ANY of the following: Serum M-protein (absolute increase ≥0.5 g/dL) Urine M-protein (absolute increase of ≥200 mg/24 hours) Bone marrow plasma cell percentage (≥ 10% absolute increase) in absence of measurable M-protein Difference in kappa & lambda free light chain levels (ratio must be abnormal; absolute change must be >10 mg/dL) Patients are also considered to have progressive disease when: New bone or soft tissue lesions (e.g. plasmacytomas) are identified; or There is an unequivocal increase in the size of previously existing lesions; or The development of an otherwise unexplained serum calcium >11.5 mg/dL Have received 1, but no more than 4 prior treatment regimens or lines of therapy for MM (Induction therapy followed by stem cell transplant & consolidation/maintenance therapy will be considered as one line of therapy) ECOG Performance status 0 - 2 Life expectancy of at least 12 weeks Evaluable MM with, at least one of the following, assessed within 21 days prior to randomization: Serum M-protein ≥ 0.5 g/dL, or Urine M-protein ≥ 200 mg/24 hour, or In absence of detectable serum or urine M-protein, serum FLC (SFLC) > 100 mg/L (involved light chain) and/or an abnormal kappa/lamda ratio (>4:1 or <2:1), or Monoclonal plasma cells in a bone marrow biopsy/aspirate of >5% Adequate organ and marrow function as defined below: - Leukocytes ≥ 2,500/mcL - Absolute neutrophil count ≥ 1,500/mcL - Platelets ≥ 100,000/mcL - Total bilirubin < 2 X ULN - AST(SGOT)/ALT(SPGT) ≤ 2.5 X ULN - Creatinine < 1.5 X ULN Contraception Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for duration of study, and for 90 days after completion of therapy. A female of child-bearing potential is considered to be any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: - No hysterectomy or bilateral oophorectomy; or - Not naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Male patients must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential. No prior therapy with pomalidomide or everolimus. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Receiving any other investigational agents. Minimum 4 week "washout" period is required. History of allergic reactions attributed to compounds of similar chemical or biologic composition to pomalidomide, everolimus, or other agents used in the study. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Pregnant or nursing (due to the rick for congenital abnormalities and the potential of this regimen to harm nursing infants). Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). Plasma cell leukemia or circulating plasma cells ≥ 2 × 10^9/L. Waldenstrom's Macroglobulinemia. Patients with known amyloidosis. Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow). Immunotherapy within 21 days prior to randomization. Myelodysplastic syndrome Major surgery (excluding kyphoplasty) within 28 days Known cirrhosis. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days Ongoing graft-vs-host disease. Using CYP3A4 inhibitors such as Ketoconazole, Ritonavir, Itraconazole, Erythromycin, Clarithromycin, Nelfinavir, Fluconazole, Amiodarone, Cyclosporine, Diltiazem, nefazadone,fluvoxamine, verapamil, chloramphenicol, Indinavir or saquinavir within 7 days of treatment. |
| 15 | NCT01902225 | completed | 0.677931547164917 | phase 1 | ['lymphoma', 't-cell lymphoma', 'cutaneous lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['istodax', 'doxil'] | ['C\\C=C1/NC(=O)[C@H]2CSSCC\\C=C\\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C', 'COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O'] | Inclusion Criteria: 1. Able to understand and voluntarily sign an informed consent form. 2. Age ≥18 years at the time of signing the informed consent form. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Biopsy-proven, measurable, Stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy (Note: extracorporeal photopheresis will be considered a systemic therapy for this study) 5. All cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. The only exceptions are participants with erythroderma who have been on corticosteroids for prolonged periods of time (>60 days) without change may continue use of either low dose systemic steroid (equivalent to <10 mg per day of prednisone) or low potency topical steroids are eligible for this study if the frequency and dosage steroids has not changed for 60 days prior to the study. These participants should continue on the same dose of systemic/topical steroid throughout the study period unless they achieve a complete response at which time steroids can be discontinued. Patients are allowed to continue any medications with known activity in T cell lymphomas at the pre-enrollment doses for conditions other than T cell lymphomas (ie, steroids for sarcoidosis) , as long as there is evidence of T cell lymphoma progression while patients were on these agents. 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry. 7. Laboratory test results within these ranges: - Absolute neutrophil count ≥750/mm³ - Platelet count≥75,000/mm³ - Total bilirubin ≤ 2 x upper limit of normal (ULN) - ULN and Aspartate Aminotransferase (ALT) (SGPT) ≤ 3 x ULN. - Creatinine < 2 mg/dL 8. Disease free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Patients with early stage of prostate cancer under clinical surveillance without therapy are eligible 9. Negative serum pregnancy test at the time of enrollment for females of childbearing potential. 10. For males and females of child-producing potential, use of effective contraceptive methods during the study to include 2 methods of contraception, one being a condom. 11. Life expectancy >90 days. Exclusion Criteria: 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2. Pregnant or breast feeding females. 3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 4. Use of any other experimental drug or therapy within 28 days of baseline except topical therapy for mycosis fungoides which must be discontinued 14 days prior to initiation of study therapy. 5. Prior allogeneic hematopoietic cell transplant. 6. Prior solid organ transplant. 7. Cumulative anthracycline exposure greater than 300 mg/m2 doxorubicin equivalents. 8. Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of prior hepatitis B virus vaccination are eligible. 9. Central nervous system or meningeal involvement 10. Any known cardiac abnormalities including: - Congenital long QT syndrome - Baseline QTc interval ≥ 480 milliseconds; - Myocardial infarction within 6 months of Cycle 1 Day 1 (C1D1). Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate - Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) - Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II- IV. In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present - An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present - Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix 10) and/or ejection fraction <40% by Multigated Acquisition Scan (MUGA) scan or <50% by echocardiogram and/or MRI - A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD) - Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes - Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients with a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria - Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers) - Any cardiac finding that is deemed ineligible at the discretion of the investigator 11. Patients taking drugs leading to significant QT prolongation and unable to stop drugs prior to treatment 12. Concomitant use of CYP3A4 inhibitors or inducers unless able to stop medication(s) prior to starting study therapies | |
| 16 | NCT01904643 | terminated | accrual factor | 0.5309935808181763 | phase 1 | ['adult acute megakaryoblastic leukemia (m7)', 'adult acute minimally differentiated myeloid leukemia (m0)', 'adult acute monoblastic leukemia (m5a)', 'adult acute monocytic leukemia (m5b)', 'adult acute myeloblastic leukemia with maturation (m2)', 'adult acute myeloblastic leukemia without maturation (m1)', 'adult acute myeloid leukemia with 11q23 (mll) abnormalities', 'adult acute myeloid leukemia with del(5q)', 'adult acute myeloid leukemia with inv(16)(p13;q22)', 'adult acute myeloid leukemia with t(16;16)(p13;q22)', 'adult acute myeloid leukemia with t(8;21)(q22;q22)', 'adult acute myelomonocytic leukemia (m4)', 'adult erythroleukemia (m6a)', 'adult pure erythroid leukemia (m6b)', 'recurrent adult acute myeloid leukemia'] | ["['C94.21', 'C94.22', 'C94.20']", "['C7A.1']", "['C93.01', 'C93.02', 'C93.00']", "['C93.Z1', 'C93.Z2', 'C93.91', 'C93.92', 'C93.01', 'C93.02', 'C93.Z0']", "['C92.01', 'C92.02', 'C92.00']", "['C92.01', 'C92.02', 'C92.00']", "['R19.5', 'H35.09', 'M26.50', 'M26.59', 'Q99.8', 'R06.89', 'R06.9']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C92.51', 'C92.52', 'C93.11', 'C93.12', 'C93.31', 'C93.32', 'C92.50']", "['C94.01', 'C94.02', 'C94.00']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']"] | ['lenalidomide', 'mitoxantrone hydrochloride', 'etoposide', 'cytarabine'] | ['NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O', 'OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O', 'OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1', 'ClCCN(CCCl)P1(=O)NCCCO1'] | Inclusion Criteria: - Patients eligible include those with diagnosis of AML other than acute promyelocytic leukemia by World Health Organization (WHO) criteria with relapsed disease after induction therapy or refractory to induction chemotherapy, as determined by morphology on bone marrow biopsy; also eligible are patients unwilling to receive standard induction chemotherapy - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Serum creatinine =< 1.5 mg/dL; if serum creatinine > 1.5 mg/dL, then the estimated glomerular filtrate rate (GFR) must be > 60ml/min/1.73m^2 as calculated by the Modification of Diet in Renal Disease equation - Serum bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation is considered to be secondary to Gilbert's syndrome, hemolysis, or hepatic infiltration by AML - Aspartate transaminase (AST)/alanine transaminase (ALT) =< 2.5 x ULN - Alkaline phosphatase =< 2.5 x ULN - All study participants must be registered into the mandatory Revlimid assistance (RevAssist) program, and be willing and able to comply with the requirements of RevAssist - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by RevAssist) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy Exclusion Criteria: - Patient must not undergo concomitant radiotherapy, chemotherapy or immunotherapy; patient must not be in concurrent study with other investigational agents - Patients who have received prior lenalidomide therapy are not eligible for this study; further there should be at least a 14-day window from the patient's last prior therapy before initiation of treatment on clinical trial - Have other severe concurrent disease or serious organ dysfunction involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo treatment - Have significant, uncontrolled active infection - Pregnant or nursing patients will be excluded from the study - Known human immunodeficiency virus (HIV) infection |
| 17 | NCT01933594 | completed | 0.6247966289520264 | phase 1/phase 2 | ['hiv infections'] | ["['Z21']"] | ['romidepsin', 'placebo for romidepsin'] | ['C\\C=C1/NC(=O)[C@H]2CSSCC\\C=C\\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: Cohorts 1, 2, & 3 - HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry & confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA - Receiving 2 (or more) nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir, dolutegravir, or efavirenz for at least 90 days prior to study entry with no intention to change for the duration of the study - Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the 1st measurement must be from a result obtained between 365-91 days, inclusive, prior to study entry. Documentation of the 2nd measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry. - CD4 cell count ≥300 cells/mm^3 obtained within 90-50 days prior to study entry at any US laboratory that has a CLIA certification or equivalent - HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay within 90-50 days prior to study entry - HIV-1 RNA level of ≥0.4 copies/mL obtained by SCA within 90-50 days prior to study entry. This result must be available prior to the pre-entry visit - The following laboratory values obtained within 21-0 days prior to study entry by any laboratory that has a CLIA certification or equivalent - ANC ≥1500 cells/mm^3 - Hemoglobin ≥12.0 g/dL for men & >11.0 g/dL for women - Platelet count ≥120,000/mm^3 - The following laboratory values obtained within 21-7 days prior to study entry by any laboratory that has a CLIA certification or equivalent - CrCl ≥60 mL/min - Potassium & magnesium within normal limits - AST (SGOT) <2.0 x ULN - ALT (SGPT) <2.0 x ULN - Alkaline phosphatase <2.0 x ULN - Total bilirubin <2.5 x ULN - HCV antibody negative result within 90-50 days prior to study entry or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained within 90-50 days prior to study entry - Negative HBsAg result obtained within 90-50 days prior to study entry or a positive HBsAb result at any time prior to study entry - For females of reproductive potential, negative serum or urine pregnancy test (latter with sensitivity of ≤25 mIU/mL) at the screening visit, pre-entry visit within 21-7 days prior to study entry, & at entry prior to romidepsin infusion, by any US laboratory that has a CLIA certification or equivalent - Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, &, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All female participants of reproductive potential must be instructed to use contraceptives for 6 months/180 days after completing RMD or placebo infusion - Karnofsky performance score ≥80 within 21-7 days prior to study entry - Men and women age ≥ 18 years - Ability & willingness to provide written informed consent - Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen Exclusion Criteria: Cohorts 1, 2, & 3 - History of or current malignancy requiring cytotoxic therapy - Bacterial, fungal, or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry - History of or current CMV end organ disease (eg, retinitis) - History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator - Chronic, acute, or recurrent infections that are current & serious in the opinion of the investigator & for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable - Active autoimmune disorders including but not limited to: inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis & optic neuritis - History of seizure disorders - History of anticonvulsant use within 60 days prior to study entry - History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome - Breastfeeding - Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry - Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study - Intent to use cytokines (e.g., IL-2 or IL-12) during the course of the study. Prior administration of cytokines is not an exclusion criterion; however, at least 60 days between the most recent cycle of any cytokine and study entry is required - Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole); dexamethasone; macrolide antibiotics (azithromycin, clarithromycin, erythromycin); ARVs that are inhibitors of, or are metabolized by, CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc); cobicistat; warfarin; nefazodone; rifamycins (rifabutin, rifampin, rifapentine); St. John's Wort; carbamazepine; phenytoin; phenobarbital; amiodarone; dofetilide; pimozide; procainamide; quinidine; sotalol; & birth control products containing estrogen; drugs that are p-glycoprotein inhibitors; & drugs that prolong the QTc interval with a risk of Torsades de Pointes - Known allergy, sensitivity, or any hypersensitivity to components of RMD or its formulation - Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry - Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements - Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry - Psychosocial conditions that would prevent study compliance and follow-up, as determined by the investigator - Documented opportunistic infections within 60 days prior to entry Inclusion Criteria: Cohort 4, Step 1 - HIV-1 infection, documented by any licensed rapid HIV test or HIV E/CIA test kit at any time prior to study entry & confirmed by a licensed Western blot or a 2nd antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA - Receiving 2 or more nucleoside or nucleotide reverse transcriptase inhibitors with raltegravir or dolutegravir for at least 90 days prior to study entry with no intention to change for the duration of the study - Documentation of at least 2 historical HIV-1 RNA measurements <50 copies/mL while on ART obtained by standard ultrasensitive assay. Documentation of the first measurement must be from a result obtained between 365-61 days, inclusive, prior to study entry. Documentation of the second measurement must be from a result obtained between 730-366 days, inclusive, prior to study entry. In addition, there must be no HIV-1 RNA values ≥50 copies/mL for at least 365 days prior to study entry - CD4 cell count ≥300 cells/mm^3 obtained between 36-60 days prior to study entry (screening visit) at any US laboratory that has a CLIA certification or equivalent - HIV-1 RNA level of <50 copies/mL obtained by standard ultrasensitive assay at screening (between 36-60 days prior to study entry) - The following laboratory values obtained at pre-entry (between 3-14 days prior to study entry) by any laboratory that has a CLIA certification or equivalent - ANC ≥1500 cells/mm^3 - Hemoglobin ≥12.0 g/dL for men & >11.0 g/dL for women - Platelet count ≥120,000/mm^3 - CrCl ≥60 mL/min - Potassium & magnesium within normal limits - AST (SGOT) <2.0 x ULN - ALT (SGPT) <2.0 x ULN - Alkaline phosphatase <2.0 x ULN - Total bilirubin <2.5 x ULN - HCV antibody negative result at screening (between 36-60 days prior to study entry) or, for study candidates who are HCV antibody positive (based on testing performed at any time prior to study entry), a negative HCV RNA result obtained at screening - Negative HBsAg result obtained at screening (between 36-60 days prior to study entry) or a positive HBsAb result at any time prior to study entry - For females of reproductive potential, negative urine pregnancy test (with a sensitivity of ≤25 mIU/mL) at screening (between 36-60 days prior to study entry), at pre-entry (between 3-14 days prior to study entry), & at entry prior to infusion, by any US laboratory that has a CLIA certification or equivalent - Female candidates of reproductive potential must refrain from participating in active attempts to become pregnant, &, if participating in sexual activity that could lead to pregnancy, must agree to use at least 2 reliable forms of contraception that are non-estrogen based. All participants of reproductive potential will be instructed to use contraceptives for 6 months or 180 days after completing RMD/placebo infusion - Karnofsky performance score ≥80 at pre-entry (between 3-14 days prior to study entry) - Men and women age ≥ 18 years - Ability & willingness to provide written informed consent - Investigator anticipates that a fully active alternative ART regimen could be constructed in the event of virologic failure on the current ART regimen Exclusion Criteria: Cohort 4, Step 1 - History of or current malignancy requiring cytotoxic therapy - Bacterial, fungal or viral infection (other than HIV) requiring systemic therapy within 30 days prior to entry - History of or current CMV end organ disease (eg, retinitis) - History of or current AIDS-related syndromes or symptoms that pose a perceived excessive risk for study drug-related morbidity, as determined by the investigator - Chronic, acute, or recurrent infections that are current & serious, in the opinion of the investigator, for which the participant has not completed at least 14 consecutive days of therapy within 30 days prior to study entry and/or is not clinically stable - Active autoimmune disorders including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis as determined by the investigator, systemic lupus erythematosus, rheumatoid arthritis, & optic neuritis - History of seizure disorders - History of anticonvulsant use within 60 days prior to study entry - History of MI within 6 months prior to study entry, history of QTc prolongation (defined as ECG with QTc intervals >450 ms) at any time prior to study entry, NYHA class III or IV heart failure at any time prior to study entry, or family history of prolonged QTc syndrome - Breastfeeding - Use of immunomodulators (eg, interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry - Any vaccination within 30 days prior to entry or intent to receive an elective vaccination (eg, flu shot, hepatitis A or B vaccine) during the course of the study - Intent to use cytokines (eg, IL-2 or IL-12) during the course of the study - Within 60 days prior to study entry, use of systemic azole antifungals (voriconazole, itraconazole, ketoconazole), dexamethasone, macrolide antibiotics (azithromycin, clarithromycin, erythromycin), antiretrovirals that are inhibitors of, or are metabolized by CYP3A4 (atazanavir, ritonavir, nelfinavir, indinavir, saquinavir, darunavir, lopinavir, rilpivirine, maraviroc), cobicistat, warfarin, nefazodone, rifamycins (rifabutin, rifampin, rifapentine), St. John's Wort, carbamazepine, phenytoin, phenobarbital, amiodarone, dofetilide, pimozide, procainamide, quinidine, sotalol, & birth control products containing estrogen, drugs that are p-glycoprotein inhibitors, & drugs that prolong the QTc interval with a risk of Torsades de Pointes - Known allergy/sensitivity or any hypersensitivity to components of RMD or its formulation - Use of histone deacetylase inhibitors (eg, vorinostat, valproic acid) at any time prior to study entry - Active illicit drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements - Acute or serious illness requiring systemic treatment and/or hospitalization that is not resolved within 30 days prior to entry - Psychosocial conditions that would prevent study compliance & follow-up as determined by the investigator - Documented opportunistic infections within 60 days prior to entry - Use of any of the medications listed in the Prohibited Medications table in the protocol See the protocol for Inclusion and Exclusion Criteria for Cohort 4, Steps 2, 3, and 4. | |
| 18 | NCT01940133 | completed | 0.7335960268974304 | phase 1 | ['advanced solid tumors'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']"] | ['pqr309'] | ['CN1N=NC2=C(N=CN2C1=O)C(N)=O'] | Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no therapy of proven efficacy is available. - Age ≥ 18 - Evidence of tumor progression with measurable or evaluable disease. - Use of adequate contraceptive measures for male patients. - Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1. - Signed informed consent. Exclusion Criteria: - Concomitant anticancer therapy (e.g., chemotherapy, radiotherapy, hormonal, immunotherapy, biological response modifier, signal transduction inhibitors) - Patients with a history of myocardial infarction or coronary artery bypass within the last 3 years. - Patients with severe/unstable angina, coronary/peripheral arterial bypass, symptomatic congestive heart failure NYHA Class 3 or 4, hypertension BP>150/100mmHg. - Pre-diagnosed diabetes mellitus. - Fasting glucose > 7.0 mmol/L or HbA1c > 6%. | |
| 19 | NCT01949532 | completed | 0.5349802374839783 | phase 1 | ['relapsed multiple myeloma', 'end-stage renal disease'] | ["['G35', 'M15.3', 'M67.49', 'M89.09', 'M89.59', 'M94.29', 'Q78.6']", "['N18.6', 'I12.0', 'I13.11', 'I13.2']"] | ['carfilzomib'] | ['CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1'] | Key Inclusion Criteria: 1. Relapsed multiple myeloma 2. Evaluable disease (serum protein electrophoresis [SPEP]/urine protein electrophoresis [UPEP]/serum free light chain [SFLC] criteria) 3. Received at least 1 prior treatment regimen or line of therapy for multiple myeloma 4. End-stage renal disease (ESRD) on hemodialysis or CrCl ≥ 75 mL/min 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 6. Adequate organ and bone marrow function 7. Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment Key Exclusion Criteria: 1. Immunoglobulin M (IgM) multiple myeloma 2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Waldenström Macroglobulinemia 4. Active congestive heart failure (NYHA Class III-IV) ischemia, conduction abnormalities 5. Known human immunodeficiency virus (HIV), recent hepatitis B virus (HBV), hepatitis C virus (HCV) 6. Myelodysplastic Syndrome 7. Contraindication to test article, constituents, or required concomitant medications 8. Other investigational drugs | |
| 20 | NCT01953809 | withdrawn | emerging gsk1322322 pre-clinical data id'd potentially reactive metabolites previously not seen that changed the risk: benefit profile and led to a termination | 0.5118013024330139 | phase 1 | ['infections, bacterial'] | ["['A49.9', 'A04.9', 'A04.8', 'A49.8']"] | ['gsk1322322', 'ee/ne', 'gsk1322322 placebo', 'ee/ne placebo'] | ['CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1', '[Ne]', 'CC1=NC(NNC(=O)[C@H](CC2CCCC2)CN(O)C=O)=C(F)C(=N1)N1CCN2CCOC[C@@H]2C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator feels that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. - Non smoking female (of childbearing age), between 18 and 45 years of age inclusive, at the time of signing the informed consent. - A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy without oophorectomy (at least one functioning ovary required) or child bearing age with the presence of non-drug eluting intra uterine device (IUD) i.e. copper. NOTE: The IUD placement needs to be confirmed by an obstetrician-gynecologist. - Subjects must be willing to use EE/NE in combination with one of the following appropriate contraceptive methods from at least 14 days prior to the first dose of study drug until completion of the follow-up visit Complete abstinence from intercourse for at least 14 days prior to the first dose of IP, throughout the study, and for the subsequent post study monitoring or; A barrier method plus a spermicide (e.g., condom or diaphragm with spermicidal foam/gel/cream/ suppository for at least 14 days prior to the first dose of IP throughout the study, and for the subsequent post study monitoring or Sterilization (vasectomy) of male partner prior to commencement of female subject's last normal menstrual period prior to IP administration and the male partner is the sole partner for that female subject - Body weight >=50 kilograms (kg) (110 pounds [lbs]) and <114kg (<250 lbs) and body mass index within the range 19 to 32 kg/meter^2 (inclusive). - Alanine aminotransferase, alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening and check-in (repeat allowed at check-in only). - QT interval corrected for heart rate by Bazett's formula (QTcB) < 450 millisecond (msec) at screening and check-in. - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Exclusion Criteria: - Pregnant females as determined by positive human chorionic gonadotropin (hCG) test at screening or prior to dosing. - History of any condition that would contraindicate Ortho-Novum administration (including hypertension, stroke, ischemic heart disease, venous thromboembolism or family history of thromboembolism, known factor V Leiden mutation or other gene mutations associated with increased risk of thromboembolism, migraine headaches, carcinoma of the breast, liver or endometrium, gallbladder disease, history of undiagnosed abnormal uterine bleeding, etc. - Females with conditions or concurrent medications that could adversely affect hormone levels (e.g. oophorectomies). - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - Endocrine system: untreated or unstable thyroid disorder and/or diabetes mellitus (I and II). Treatment of the condition must be stable for at least 4 weeks prior to first dose of study drug. - Have suffered a urinary tract, bladder, or vaginal infection within 4 weeks prior to the first dose of study drug, or has a urinalysis result at Screening consistent with an urinary tract infection. Subjects diagnosed with an infection at Screening should be treated appropriately and may be re-screened after 4 weeks. - Fasting triglycerides > 300 mg/deciliter (dL) at Screening. - A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or a positive test for human immuno virus (HIV) antibody result within 3 months of screening. - A positive pre-study drug/alcohol screen. - History of regular alcohol consumption within 6 months of the study defined as An average weekly intake of >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. - Concurrent-medications that alter gastro-intestinal motility result in diarrhea or bind study drugs (for example erythromycin, antacids, prokinetic agents, cholestyramine). - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). - Exposure to more than four new chemical entities within 12 months prior to the first dosing day. - Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety due to potential drug interaction. - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. - Lactating females. - History of sensitivity to heparin or heparin-induced thrombocytopenia. - Urinary cotinine levels indicative of smoking or regular use of tobacco- or nicotine-containing products within 4 weeks prior to screening. - Unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication. - Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Female subjects with Heart rate <50 and >100 beats per minute (bpm), PR interval <120 and >220 msec, QRS duration <70 and >120 msec, QTcB >=450 msec (Note: The waveforms must enable the QT interval to be clearly defined), Q wave>30 msec Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right bundle branch block, AV block (2nd degree or higher), Wolf Parkinson White (WPW) syndrome), sinus pauses> 3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GSK medical monitor, will interfere with the safety of the individual subject. |
| 21 | NCT01954732 | withdrawn | slow accrual | 0.36075589060783386 | phase 1 | ['stage ia pancreatic cancer', 'stage ib pancreatic cancer', 'stage iia pancreatic cancer', 'stage iib pancreatic cancer'] | ["['C25.3']", "['C25.3']", "['C25.3']", "['C25.3']"] | ['metformin hydrochloride'] | ['CN(C)C(=N)NC(N)=N'] | Inclusion Criteria: - Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible - Patients must be previously untreated with chemotherapy or radiation therapy - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded - Hemoglobin (Hg)A1C must be below 7% - Total bilirubin less than 1.5 X institutional upper limit of normal - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal - Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal - Serum creatinine within normal institutional limits - Alkaline phosphatase < 1.5 X institutional upper limit of normal - Subjects must have the ability to understand and be willing to provide written informed consent Exclusion Criteria: - History of metformin use in the previous 3 months - Treatment with neoadjuvant chemotherapy or radiation therapy - History of allergic reactions attributed to metformin - Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Metabolic acidosis, acute or chronic, including ketoacidosis - Metastatic disease |
| 22 | NCT01965600 | terminated | 0.6723794937133789 | phase 1 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['pf-06282999', 'placebo', 'pf-06282999', 'placebo'] | ['COC1=CC=C(Cl)C=C1C1=CC(=O)NC(=S)N1CC(N)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'COC1=CC=C(Cl)C=C1C1=CC(=O)NC(=S)N1CC(N)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Healthy men or women (non-childbearing potential) between the ages of 18-40 years. - Body Mass Index (BMI) 18-30 kg/m2 and a total body weight >50 kg (110 lbs). Exclusion Criteria: - History or evidence of habitual use of tobacco- or nicotine-containing products within 3 months of screening. - History of frequent headaches or migraines (>3 per month), or headaches from an absence of caffeine. - Caffeine consumption in excess of 3 cups per day. - Subjects who have experienced cold/flu symptoms (ie, runny nose, cough, and/or fever) within 2 weeks of the first administration of study drug/placebo of each period. - History of recurrent or chronic infections of any type such as tuberculosis, sinusitis, urinary tract infection, respiratory tract or dental (abscess) infection, etc. Also excluded are subjects with recurrent oral or genital herpes, recurrent herpes zoster, or any infection otherwise judged by the investigator to have the potential for worsening if enrolled in this study. - Treatment with LPS in the past 12 months and/or a history of an allergic type reaction or known hypersensitivity to endotoxin at any time. | |
| 23 | NCT01966731 | active, not recruiting | 0.4929376542568207 | phase 1/phase 2 | ['sickle cell disease'] | ["['D57.1', 'D57.20', 'D57.212', 'D57.219', 'D57.211', 'D57.213', 'D57.218']"] | ['hydroxyurea'] | ['NC(=O)NO'] | Inclusion Criteria 1. Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear) 2. Age range of 1.00-9.99 years, inclusive, at the time of enrollment 3. Weight at least 10.0 kg at the time of enrollment 4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements 5. Willingness to comply with all study-related treatments, evaluations, and follow-up Exclusion Criteria 1. Known medical condition making participation ill-advised, (e.g., acute or chronic infectious disease, HIV, or malignancy) 2. Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or weight-for-length/height >3 z-scores below the median WHO growth standards, as defined in Appendix I) 3. Pre-existing severe hematological toxicity (temporary exclusions) 1. Anemia: Hb <4.0 gm/dL 2. Anemia: Hb <6.0 gm/dL with ARC <100 x 109/L 3. Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 gm/dL 4. Thrombocytopenia: Platelets <80 x 109/L 5. Neutropenia: ANC <1.0 x 109/L 4. Blood transfusion within 60 days before enrollment (temporary exclusion) 5. Hydroxyurea use within 6 months before enrollment | |
| 24 | NCT01972711 | completed | 0.5531315803527832 | phase 1 | ['schizophrenia'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']"] | ['sep-363856', 'amisulpride', 'placebo'] | ['ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Male or female aged 18 to 45 years, inclusive, at Day 1. - Subject must be healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring within four weeks of randomisation. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. - Subject must be normotensive with sitting (5 minutes) blood pressure between the range of 90 to 150 mm Hg systolic, inclusive, and 60 to 90 mm Hg diastolic, inclusive, at Screening. - Subject must have sitting (5 minutes) heart rate ≥ 50 beats per minute at Screening. - Subject must agree to use one of the following birth control/contraception methods from Screening until 90 days after receiving study drug. - Female subject of child bearing potential (≤ 65 years) should be surgically sterile or abstinent or, if sexually active, must use an adequate method of contraception in addition to their partner(s) using a barrier method. - Male subject with female partner(s) of childbearing potential must take appropriate precautions to avoid fathering a child and use barrier contraception, in addition to their female partner(s) using another method. - Male subject must not donate sperm. - Acceptable forms of contraception are as follows: - Barrier methods: condoms, diaphragms, cervical caps; with a spermicide foam, gel, film, cream or pessary. - Non-hormone containing intrauterine methods: intrauterine devices or systems. - Other: prescription oral contraceptives, contraceptive injections, contraceptive implant, contraceptive vaginal ring, hormonal intrauterine device, double-barrier method, contraceptive patch, or male partner sterilisation. - Subject must have normal ECG results, including QTcF < 450msec (for men) or < 470 ms (for women) (based on the Fridericia correction where QTcF = QT/RR0.33) at Screening. - Subject must be a completely fluent English speaker who, in the opinion of the Investigator, is capable of completing the fMRI and behavioural tasks. - Subject must be right-handed. - Subject must have acceptable weight as defined by BMI (weight [kg]/height [m]²) range of 18 to 35 kg/m², inclusive at Screening. - Subject must be a non-smoker or light smoker (≤ 10 cigarettes per day). - Subject must have signed the informed consent form prior to the first study-related procedure indicating they understand the purpose of and procedures required for the study and are willing to participate in the study. - Subject in the low schizotypy group must have an SPQ score < 10 at Screening. - Subject in the high schizotypy group must have an SPQ score >43 at Screening Exclusion Criteria: - Subject with a history of alcohol or substance dependence within the last 12 months from Screening. - Subject with a positive urine drug screen at Screening or Day 1. One re-test within 1 to 3 days is permitted if positive result is believed to be due to licenced opiate-based medication or ingestion of poppy seeds. In this event, re-test result will be used for assessing entry criterion and must be completed prior to randomisation. - Subject with a positive alcohol breath test at Screening or Day 1. - Female subject with a positive pregnancy test at Screening or Day 1. - Female subject currently pregnant or trying to get pregnant or currently breast feeding. - Subject who consumes large amounts of caffeinated drinks (more than 8 cups of standard caffeinated drinks (tea, instant coffee) or 6 cups of stronger coffee or other drinks containing methylxanthines such as coca cola or Red Bull per day). - Subject with a relevant history, or presence upon clinical examination, of cardiac, ophthalmologic, pulmonary, endocrine (diabetes), blood disease, gastro-intestinal, hepatic or renal disease or other condition which in the opinion of the Investigator could interfere with the test procedures. - Subject with a history of cancer, except for basal cell or Stage 1 squamous cell carcinoma of the skin which has been in remission for at least 5 years prior to Day 1. - Subject meets the diagnostic criteria for schizophrenia, or any other psychotic disorder, as determined by the SCID-I at Screening - Subject with a history of, or presents (in the opinion of the Investigator) with, significant neurological or psychiatric conditions (such as stroke, traumatic brain injury, depression, seizures, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, blackouts requiring hospitalisation). - Subject with a history of positive HIV test. - Subject with a history of, or current condition of, migraine headaches or has undergone operations to the head. - Subject with a significant hearing impairment which, in the opinion of the Investigator, may interfere with the performance of the behavioural tasks or fMRI tasks. - Subject with a significant visual impairment including colour blindness, or history of ocular treatment including corrective laser eye surgery, or ongoing condition, which in the opinion of the Investigator may interfere with the performance of the behavioural tasks or fMRI tasks. - Subject received prescribed medication within 28 days prior to Day 1 (apart from the contraceptive pill). Subjects who have taken prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety (see Section 10.2, Concomitant Medications). - Subject received non-prescription medication, including supplements such as vitamins and herbal supplements within 48 hours prior to Day 1 (apart from paracetamol). Subjects who have taken non-prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety (see Section 10.2, Concomitant Medications). - Subject received an experimental drug and / or used an experimental medical device within 30 days of randomisation or within a period less than 5 times the drug's half-life, whichever is longer. - Subject with a known hypersensitivity to SEP-363856 or amisulpride or any of their excipients. - Subject with a history of severe drug allergy or hypersensitivity. - Subject who is unable or unwilling to comply with study procedures, including study prohibitions and restrictions (see Section 10.2, Concomitant Medications and Section 10.3, Restrictions). - Subject with previous experience with the ETB. - Subject with a diagnosis of dyslexia. - Subject with a history of claustrophobia or inability to tolerate scanner environment. - Subject who fulfills any of the MRI contraindications on the standard site radiography screening questionnaire (e.g. history of surgery involving metal implants). - Subject with a clinically relevant structural brain abnormality as determined by prior MRI scan. - Subject with planned medical treatment within the study period that might interfere with the study procedures. - Subject who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator. - Subject is a staff member or the relative of a staff member, or is in a subordinate relationship with the Investigator. - Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS. | |
| 25 | NCT01975688 | terminated | slow recruitment | 0.4906337261199951 | phase 1 | ['head and neck squamous cell carcinoma'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['sativex'] | ['[H][C@@]12C=C(C)CC[C@@]1([H])C(C)(C)OC1=C2C(O)=CC(CCCCC)=C1'] | Inclusion Criteria: - Subject is willing and able to give informed consent for participation in the study. - Male or female subjects aged 18 years or above. - Subject is diagnosed with Stage III or Stage IV HNSCC. - Subject is due to undergo radiotherapy of the head and/or neck with or without concomitant chemotherapy with a likelihood (in the investigator's opinion) of developing mild, moderate and severe oral mucositis. - Subject is able (in the investigator's opinion) and willing to comply with all study requirements. - Subject is willing and able to communicate with the investigator. - Subject has acceptable haematological and biochemical function, in the opinion of the investigator, as demonstrated by appropriate laboratory parameter levels including liver and renal function (estimated glomerular filtration rate as measured by the Cockcroft-Gault formula >0.5 lower limit of normal, aspartate aminotransferase/alanine aminotransferase <2.5 the upper limit of normal (ULN) and bilirubin <1.5 ULN), and in the opinion of the investigator, acceptable bone marrow reserve. - Vital signs at screening (after five minutes resting measured in the supine position) must be within the following ranges: i. Body temperature between 35.0-37.5°C ii. Systolic blood pressure, 90-150 mmHg iii. Diastolic blood pressure, 60-90 mmHg iv. Pulse rate, 40-99 beats per minute Blood pressure and pulse rate will be taken again in a standing position. After two minutes standing, there shall be no more than a 20 mmHg drop in systolic or 10 mmHg drop in diastolic blood pressure, associated with clinical manifestation of postural hypotension. - Subject has an Eastern Co-operative Oncology Group Performance Status of 0, 1 or 2. - Subject is willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries. - Subject is willing to allow his or her primary care practitioner and consultant to be notified of participation in the study. Exclusion Criteria: - Subjects undergoing chemotherapy only. - Subjects with cancer other than HNSCC as the primary tumour. - Subjects who have undergone reconstructive oral surgery for HNSCC (within the last eight weeks). - Subjects with RTOG Grade 4 oral mucositis (necrosis or deep ulceration, with or without bleeding). - Subjects requiring hospital admission or extended hospitalisation for total parenteral nutrition, intravenous analgesia and/or intravenous antibiotics for the treatment of oral mucositis. - Subjects with aphthous stomatitis, herpetic mucositis, oral thrush, denture/oral trauma, gangrenous stomatitis, acute necrotising stomatitis or other oral condition that may in the opinion of the investigator affect the oromucosal absorption of Sativex® in the absence of oral mucositis. - Any surgical or medical condition, significant disease or disorder or any finding on physical examination (or oral examination) (other than their underlying condition) which might significantly alter the absorption, distribution, metabolism or excretion of drugs or that, in the opinion of the investigator, may put the subject at risk, influence the result of the study, or the subjects' ability to participate in the study. - Clinical evidence of acute or chronic liver disease or liver injury as indicated by clinically significant abnormal liver function tests such as aspartate aminotransferase, alanine aminotransferase, gamma glutamyl-transpeptidase, alkaline phosphatase, (any ≥2.5 ULN ) or serum bilirubin (≥1.5 ULN) unless there is another more likely explanation (e.g. Gilbert's syndrome). - Any change in medication within 14 days prior to dosing and throughout the study which might significantly alter the absorption, distribution, metabolism or excretion of the investigational medicinal product (IMP), in the opinion of the investigator. - History of drug abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations. - Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP(s). - Positive result for the presence of hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus antibodies. - Currently using or has used cannabis, cannabinoid-based medications (e.g. Marinol®, Nabilone®, Cannador®) or Acomplia® (rimonabant) or taranabant within 30 days of study entry and unwilling to abstain for the duration of the study. - Any known or suspected history or family history of schizophrenia, or other psychotic illness, history of severe personality disorder or other severe significant psychiatric disorder other than depression associated with underlying condition. - Any history of epilepsy as evidenced by one or more seizures in the last 12 months. - Significant cardiac disease, or has a cardiac disorder that in the opinion of the investigator would put the subject at risk of a clinically relevant arrhythmia or myocardial infarction, or has a secondary or tertiary atrioventricular block, or evidence of clinically significant cardiac disease on electrocardiogram at screening. - Female subjects of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use two effective forms of contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (Note: a male condom should not be used in conjunction with a female condom). - Female subjects who are pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter. - Subjects who have received an IMP within the 12 weeks prior to the screening visit. - Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study. - Following a physical examination, the subject has any abnormalities that, in the opinion of the investigator would prevent the subject from safe participation in the study. - Unwilling to abstain from donation of blood during the study. - Travel outside the country of residence planned during the study. - Subjects previously enrolled into this study. |
| 26 | NCT01980667 | completed | 0.7302109003067017 | phase 1 | ['advanced solid tumors'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']"] | ['lurbinectedin (pm01183)', 'cisplatin'] | ['COC1=CC=C2NC3=C(CCN[C@]33CS[C@H]4[C@H]5[C@@H]6N(C)[C@@H](CC7=C6C(O)=C(OC)C(C)=C7)[C@H](O)N5[C@@H](COC3=O)C3=C4C(OC(C)=O)=C(C)C4=C3OCO4)C2=C1', '[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC'] | Inclusion Criteria: - Voluntarily signed written informed consent - Age ≥ 18 years old - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 1. - Life expectancy ≥ 3 months. - Patients with confirmed diagnosis of advanced solid tumors. - Patients may have received ≤ 2 chemotherapy-containing lines in the advanced setting. - Adequate bone marrow, renal, hepatic, and metabolic function (assessed ≤ seven days before inclusion in the study) - Recovery or stabilization to grade ≤ 1 from any adverse event derived from previous treatment (up to grade 2 alopecia or asthenia/fatigue are allowed). - No clinically significant changes in ECG. - At least four weeks since the last monoclonal antibody containing therapy or definitive radiotherapy (RT) - At least two weeks since the last biological/investigational single-agent therapy (excluding MAbs) and/or palliative RT (≤10 fractions or ≤30 Gy total dose) - Fertil women must have pregnancy excluded by appropriate testing before study entry Exclusion Criteria: - Prior treatment with PM01183 or trabectedin. - Concomitant diseases/conditions: - History within the last year or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically relevant valvular heart disease or symptomatic arrhythmia or any asymptomatic ventricular arrhythmia requiring ongoing treatment. - Ongoing, non-neoplastic, chronically active liver disease of any origin. - Active infection. - Patients who are requiring any ongoing oxygen support. - Known human immunodeficiency virus (HIV) infection. - Any other major illness. - Symptomatic or corticosteroid-requiring brain metastases or leptomeningeal disease involvement. Patients with asymptomatic documented stable brain metastases not requiring corticosteroids during the last three months are allowed. - Peripheral sensory/motor neuropathy grade >1. Hearing impairment grade >1. - Fertile men or women not using an effective method of contraception. - History of bone marrow or stem cell transplantation - Radiotherapye to >35% of the bone marrow. | |
| 27 | NCT01981499 | terminated | the trial was prematurely terminated on 01april2014 due to safety concerns. | 0.6943349838256836 | phase 1 | ['migraine'] | ["['G43.B1', 'G43.D1', 'G43.B0', 'G43.D0', 'G43.A1', 'G43.411', 'G43.419']"] | ['pf-05180999', 'placebo', '120 mg mr pf-05180999', '360 mg mr pf-05180999', '10 mg cetirizine', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'OC(=O)COCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Healthy male subjects between the ages of 18 and 55 years - No history of clinically-relevant atopic or dermatological disease - Positive reaction to intradermal injection of histamine Exclusion Criteria: - Subjects with screening laboratory test results that deviate from the upper and/or lower limits of the reference or acceptable range. The exception is that all liver function tests must not exceed the upper limit of normal. - Subjects with evidence of, or history of, hepatic disorder, including acute or chronic hepatitis B or hepatitis C - Intolerance to intradermal histamine injection. - Subjects with dark skin (Part B only). |
| 28 | NCT01982435 | completed | 0.7407808899879456 | phase 1/phase 2 | ['diabetic macular edema'] | ["['E10.311', 'E10.319', 'E11.311', 'E11.319', 'E13.311', 'E13.319', 'E10.3513']"] | ['ranibizumab', 'ranibizumab'] | ['CN\\C(NCCSCC1=CC=C(CN(C)C)O1)=C/[N+]([O-])=O', 'CN\\C(NCCSCC1=CC=C(CN(C)C)O1)=C/[N+]([O-])=O'] | Inclusion Criteria: - Subjects will be eligible if the following criteria are met: - Ability to provide written informed consent and comply with study assessments for the full duration of the study - Age > 18 years - ETDRS best-corrected visual acuity of 20/25 to 20/320 in the study eye - Willing, committed, and able to return for ALL clinic visits and complete all study related procedures - At least 6 previous bevacizumab injections for diabetic macular edema in the last 12 months in the study eye. - At least 2 bevacizumab injections within 10 weeks and the most recent bevacizumab injection within 6 weeks of baseline study visits in the study eye. - Persistent foveal-involving diabetic macular edema based on presence of intraretinal and/or subretinal fluid by SDOCT in the foveal center at study entry in the study eye. Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from this study: - Pregnancy (positive pregnancy test) or lactation - Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD (intrauterine device), or contraceptive hormone implant or patch. - Intravitreal steroid or periocular steroid treatment within 3 months of study entry in the study eye. - Focal/grid laser photocoagulation treatment within 3 months of study entry in the study eye. - Panretinal photocoagulation treatment within 3 months of study entry in the study eye. - Prior vitrectomy in the study eye - History of retinal detachment in the study eye - Prior trabeculectomy or other filtration surgery in the study eye - Active intraocular inflammation in either eye - Active ocular or periocular infection in either eye - Active scleritis or episcleritis in either eye - History of any other retinal vascular disease (e.g., retinal vein occlusion, retinal artery occlusion) in the study eye. - Coexistent retinal disease other than diabetic retinopathy (e.g., AMD (age related macular degeneration), inherited retinal disease) in the study eye. - Intraocular surgery within 3 months of study entry in the study eye. - History of corneal transplant or corneal dystrophy in the study eye. - Significant media opacities in study eye which may interfere with visual acuity in the study eye. - Participation as a subject in any clinical study within 3 months of study entry. - History of allergy to topical iodine - Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated - Participation in another simultaneous medical investigation or trial | |
| 29 | NCT01986751 | terminated | failure to enroll | 0.5160189270973206 | phase 1/phase 2 | ['pain'] | ["['N50.82', 'R07.2', 'R07.82', 'R10.13', 'R10.33', 'R14.1', 'R52']"] | ['clonidine', 'ropivacaine'] | ['ClC1=CC=CC(Cl)=C1NC1=NCCN1', '[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C'] | Inclusion Criteria: 1. Patient undergoing foot or ankle surgery with popliteal nerve block planned for postoperative analgesia. 2. Adult, 19 years of age and older. 3. Subject classified as American Society of Anesthesiology (ASA) class 1, 2, or 3. The ASA defines these statuses as follows: 1-A normal healthy patient. 2-A patient with mild systemic disease. 3-A patient with severe systemic disease. - Exclusion Criteria: 1. Any subject not classified as an ASA 1, 2, or 3. 2. Allergy/intolerance to local anesthetic, clonidine, and/or oxycodone. 3. Subject with a history of continuous opioid use for greater than one month prior to surgery. 4. Pre-existing neurologic deficit in lower extremity (surgical site). 5. Clinically significant coagulopathy (hemophilia, von Willebrand disease). 6. Patients who fail to follow the UAB Department of Anesthesiology Algorithm for the Preoperative Management of an Angiotensin Converting Enzyme Inhibitor (ACEI) or an Angiotensin Receptor Blocker (ARB). A copy of the algorithm can be found in Appendix 1. - |
| 30 | NCT01988493 | active, not recruiting | 0.4874550998210907 | phase 1/phase 2 | ['carcinoma, hepatocellular'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['tepotinib 300 mg', 'tepotinib 500 mg', 'tepotinib 1000 mg', 'tepotinib', 'sorafenib'] | ['CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1'] | Inclusion Criteria: - Histologically or cytologically confirmed HCC - Participants were either intermediate HCC of BCLC Stage B, who were not eligible for surgical and/or local-regional therapies or who had progressive disease (PD) after surgical and/or local-regional therapies (note: the local-regional therapy must not contain sorafenib), or advanced HCC of BCLC Stage C - Participants who had disease progression on or were intolerant to the prior standard treatment for advanced HCC (phase Ib Korean subjects only) - A tumor biopsy was required for determining MET status - MET+ status (Phase 2 only), as determined by the central laboratory (Phase 1b retrospectively, Phase 2 for participant selection) were defined in the protocol - Child-Pugh class A with no encephalopathy according to the screening assessment - Asian male or female, 18 years of age or older - Measurable disease in accordance with RECIST v1.1 (Phase 2 only) - Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 - Eligible for treatment with sorafenib, was assessed by investigators according to the Package Insert and clinical judgment (Phase 2 only) - Signed and dated informed consent indicating that the participants had been informed of all the pertinent aspects of the trial prior to enrollment - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures - Life expectancy was judged by the investigator of at least 3 months Exclusion Criteria: - Prior systemic anticancer treatment for advanced HCC, included targeted therapy (for example, sorafenib), chemotherapy, or any other investigational agent (Phase 2 only) - Prior treatment with any agent targeting the hepatocyte growth factor (HGF)/c-Met pathway - Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment - Prior history of liver transplant - Laboratory index at baseline were defined in the protocol - Past or current history of neoplasm other than HCC, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years - Known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated - Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested products - Clinically significant gastrointestinal bleeding within 4 weeks before trial entry - Peripheral neuropathy Grade greater than or equal to 2 (Common Terminology Criteria for Adverse Events [CTCAE] v4.0) - Impaired cardiac function was defined in the protocol - Hypertension uncontrolled by standard therapies - Participants with a family history of long QT syndrome or who take any agent that is known to prolong QT/QTc interval - Known human immunodeficiency virus (HIV) infection - Particpants who had acute pancreatitis and/or chronic pancreatitis, with elevated lipase and/or amylase, clinical symptoms, and/or imaging studies that are indicative of the diagnosis (Mainland Chinese participants only) - Known or suspected drug hypersensitivity to any ingredients of sorafenib (Phase 2 only) and MSC2156119J - Female participants who were pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug - Concurrent treatment with a non-permitted drug - Substance abuse, other acute or chronic medical or psychiatric condition, or laboratory abnormalities that may increase the risk associated with trial participation in the opinion of the investigator - Participation in another clinical trial within the past 28 days - Previous anticancer treatment-related toxicities not recovered to baseline or Grade 0-1 (except alopecia and peripheral neuropathy) - Participants with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the investigators | |
| 31 | NCT01992952 | active, not recruiting | 0.553848922252655 | phase 1/phase 2 | ['estrogen receptor positive breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['azd5363', 'placebo', 'fulvestrant'] | ['[H][C@@](CCO)(N=C(O)C1(N)CCN(CC1)C1=NC=NC2=C1C=CN2)C1=CC=C(Cl)C=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(O)C=C3C[C@@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)[C@@]21[H]'] | Inclusion Criteria: - Post-menopausal Women - Life expectancy 3 months - Histological confirmation of ER+ breast cancer - Clinical or histological confirmation of metastatic or locally advanced disease not amenable to surgical resection - Measurable or non-measurable disease - Adequate bone marrow, renal and hepatic function - Eastern Cooperative Oncology Group (ECOG) performance status < or equal to 2 - Progressive disease whilst receiving an aromatase inhibitor (AI) for metastatic breast cancer (MBC) - Relapsed with metastatic disease whilst receiving an AI in adjuvant setting - Up to 3 prior lines of endocrine therapy for Advanced Breast Cancer - Up to 1 line of chemotherapy for Advanced Breast Cancer - Patient willing to donate archival tumour sample - Patient willing to donate baseline blood sample - Suitable for further endocrine therapy Exclusion Criteria: - Previous treatment with fulvestrant or PI3K/mTOR(mammalian target of rapamycin )/Akt inhibitor therapy - Treatment with chemotherapy, immunotherapy or targeted, biologic or tumour embolisation within 21 days of study drug administration - Palliative radiotherapy within 7 days of study drug - Clinically significant abnormalities in glucose metabolism - Rapidly progressive visceral disease not suitable for further endocrine therapy - Known brain or leptomeningeal metastases - Any co-existing medical condition precluding trial entry including significant cardiac disease (to be defined in the protocol) - Concomitant medication unsuitable for combination with trial medication | |
| 32 | NCT02000700 | completed | 0.9293985366821289 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['canagliflozin 100 mg', 'canagliflozin 50 mg', 'canagliflozin 300 mg', 'placebo'] | ['[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1', '[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1', '[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Diagnosed with Type 2 Diabetes Mellitus - Be on a stable regimen of metformin immediate release (IR) monotherapy of at least 1,000 mg/day for at least 8 weeks before screening - Able to swallow whole tablets - Absence of pancreatic autoimmunity - Participants and their caregivers must agree to perform the fasting fingerstick glucose self-monitoring during the study Exclusion Criteria: - History of Type 1 diabetes mellitus - History of maturity onset diabetes of the young (MODY) and any secondary form of diabetes - Current clinically significant medical illness e.g., significant pulmonary disease, renal or hepatic insufficiency, uncontrolled thyroid disease - Systolic or diastolic blood pressure outside the range considered normal for the participant sex, age and height - For females, participants will be excluded if pregnant | |
| 33 | NCT02009488 | completed | 0.9281951189041138 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['canagliflozin, 100 mg', 'canagliflozin, 300 mg', 'placebo'] | ['[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1', '[H][C@]1(O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)C1=CC=C(C)C(CC2=CC=C(S2)C2=CC=C(F)C=C2)=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Must have a diagnosis of T2DM for at least 3 months and be on either metformin monotherapy at a stable dose of >=1,000 mg per day or on combination therapy of metformin >=1,000 mg per day and a DPP-4 inhibitor at stable daily doses for at least 12 weeks prior to screening with an HbA1c of >=7.0% and <= 9.5% at Screening - Fasting plasma glucose >=120 mg/dL and <=240 mg/dL at the Week -4 visit - Fasting fingerstick glucose >=120 mg/dL and <=240 mg/dL performed at clinical research center on Day -14 - Must be medically stable on the basis of clinical laboratory tests performed at screening Exclusion Criteria: - Has a history of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or β-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy - Has claustrophobia or anxiety, related to previous negative experiences with magnetic resonance imaging procedures which cannot be managed with an anxiolytic drug - Has a history of brittle or labile glycemic control, with widely varying glucose measurements - Has proliferative diabetic retinopathy (based on an eye examination within one year prior to Screening), currently receiving or requiring treatment - Has a history of 1 or more severe hypoglycemic episodes within 6 months before screening - Has history of hereditary glucose-galactose malabsorption or primary renal glucosuria. | |
| 34 | NCT02013128 | completed | 0.615990400314331 | phase 1/phase 2 | ['chronic lymphocytic leukemia', 'mantle cell lymphoma'] | ["['C91.11', 'C91.12', 'C91.10']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['ublituximab', 'ibrutinib'] | ['NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1'] | Inclusion Criteria: - Confirmed Mantle Cell lymphoma (MCL) open for enrollment. The Chronic Lymphocytic Leukemia (CLL) enrollment arm is now closed. - Refractory to or relapsed after at least 1 prior treatment regimen - Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 Exclusion Criteria: - Any major surgery, chemotherapy or immunotherapy within the last 21 days - Known hepatitis B virus, hepatitis C virus or HIV infection - Autologous hematologic stem cell transplant within 3 months of study entry. Prior Allogeneic hematologic stem cell transplant is excluded. - Richter's transformation, prolymphocytic leukemia or primary central nervous system lymphoma | |
| 35 | NCT02013362 | completed | 0.6789164543151855 | phase 1/phase 2 | ['peripheral t-cell lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['pralatrexate injection'] | ['NC1=NC2=NC=C(CC(CC#C)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N=C2C(N)=N1'] | Inclusion Criteria: - Japanese patients at least 20 years of age. - Patients histologically diagnosed with peripheral T-cell lymphoma by pathological diagnosis of biopsied lesion. - Relapsed or refractory patients with a treatment history of at least one regimen. - Patients with an enlarged lymph node or extranodal mass lesion clearly measurable in two perpendicular directions and greater than 1.5 cm in maximum diameter on computed tomography performed. - Patients expected to survive for at least 3 months. - ECOG PS 0-2. - Patients with adequate hemopoietic efficacy, liver and kidney function. - Patients from whom written consent has been obtained prior to study initiation. Exclusion Criteria: - Patients who received a chemotherapy agent or a high dose of a systemic adrenocorticosteroid within 21 days prior to initial administration of the study drug. - Patients who received radiation therapy, phototherapy, or electron beam therapy within 21 days prior to initial administration of the study drug. - Patients who received another study drug within 28 days prior to initial administration of the study drug. - Patients who received antibody therapy within 100 days prior to initial administration of the study drug. - Patients with a history of allogeneic hematopoietic stem cell transplantation. Or patients with a history of autologous hematopoietic stem cell transplantation within 100 days prior to initial administration of the study drug. - Patients with cerebral metastasis or central nervous system lesion or a past history. - Patients with active multiple primary cancer. Or patients with a history of a malignant neoplasm other than peripheral T-cell lymphoma within the past 5 years. - Patients with severe cardiovascular disease. - Patients positive for HBs antigen, HCV antibody or HIV antibody on immunological investigation. Or patients positive for either HBc antibody or HBs antibody, and showing DNA more than sensitivity in HBV-DNA assay. - Patients positive for CMV antigen on immunological investigation. - Patients with infectious disease requiring treatment consisting of intravenous administration of antibacterial agent, fungicide, or antiviral drug. - Patients with interstitial pneumonia or pulmonary fibrosis, or patients judged to have insufficient pulmonary function. | |
| 36 | NCT02018523 | terminated | study did not enroll enough subjects to make a statistically sound conclusion. | 0.5960102677345276 | phase 1 | ['carcinoma, non-small-cell lung'] | ["['D02.20', 'D02.21', 'D02.22']"] | ['lenalidomide'] | ['NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O'] | Inclusion Criteria: - Patients must have histologically or cytologically confirmed stage IIIB or stage IV NSCLC with measurable disease at initial presentation prior to chemotherapy. See Section 8.4.1 for measurable disease parameters. - Patients must have had a complete response (CR), partial response (PR) or stable disease (SD) after 4-6 cycles of first-line chemotherapy. Tumor response will be assessed by RECIST criteria version 1.1. - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, or radiotherapy before entering this study. 1. Myelosuppressive chemotherapy: At least 21 days elapsed from end of treatment before registration (42 days if prior nitrosourea). 2. Hematopoietic growth factors: At least 7 days since the completion of therapy with a growth factor. 3. Other: For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. 4. XRT: > or = to 2 weeks for local palliative XRT (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if other substantial bone marrow radiation. - Patients must be > or = 18 years of age. - ECOG performance status < or = to 1 (Karnofsky > 70%). - Organ Functions: Patients must have normal organ and marrow function as defined below within 28 days of registration: 1. Leukocytes > or = 3,000/uL 2. Absolute neutrophil count > or = 1,500/uL 3. Hemoglobin > or = 8 g/dL 4. Platelets > or = 100,000/uL 5. Total bilirubin 1.5X institutional upper limit of normal (ULN) 6. AST (SGOT) and ALT (SGPT) 1.5X institutional ULN 7. Creatinine clearance > or = 60 mL/min/1.73 m2 for patients with creatinine levels > institutional normal - All study participants must be willing and agree to be registered into the mandatory REVLIMID REMS program, and be willing and able to comply with the requirements of REVLIMID REM. REVLIMID REMS registration does not need to be complete to determine study eligibility. - Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days before registration. Treating investigator must affirm intention to perform another serum or urine UPT 24 hours before initiating lenalidomide treatment. *FCBP: A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). - All patients must be counseled about pregnancy precautions, risks of fetal exposure and other risks. The counseling must be done before the initiation of the study and every 28 days before the study drug is dispensed to the subject. FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix D: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. - Able to take aspirin (81 mg) daily as prophylactic anticoagulation (Patients intolerant to ASA may use warfarin or low molecular weight heparin). - Able to understand and willing to sign a written informed consent document. - Life expectancy > or = 12 weeks Exclusion Criteria - Concomitant Medications: 1. Patients may not be receiving any other anti-cancer therapy. 2. Patients may not be receiving any other investigational agents. 3. Patients may not be receiving systemic steroids or other immunosuppressive drugs; however, steroid containing inhaler may be allowed after discussing with the Principal Investigator. Duration of 5 half-lives must have elapsed before the study registration if the patient was on systemic steroids or other immunosuppressive drugs. - Patients with untreated brain metastasis, or with treated brain metastasis but requiring steroids. - Patients with known EGFR mutation or EML-ALK fusion gene and with stage IV disease. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide or thalidomide. - The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. - Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, cardiac arrhythmia, autoimmune disease or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant or breastfeeding women are excluded from this study because lenalidomide has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. - Known sera-positive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. - Any other clinically significant medical condition and/or organ dysfunction that will interfere with the administration of the therapy according to this protocol or which, in the views of investigator, preclude combination chemotherapy. |
| 37 | NCT02023424 | unknown status | 0.7270166873931885 | phase 1 | ['rett syndrome'] | ["['F84.2']"] | ['glatiramer acetate (copaxone®)'] | ['CC(O)=O'] | Inclusion Criteria: 1. Females, age 6-15 years (inclusive). 2. Patients whose parents or legal custodians have provided written informed consent to participate in the study. 3. A diagnosis of RTT (classical or variant), defined according to the internationally agreed 2010 RetSearch criteria [4]. 4. Evidence of a genetically defined pathological change in the MECP2 gene (point mutation or deletion) 5. Patients with known epileptiform activity as recorded on EEG. 6. Blood pressure and heart rate within normal limits (blood pressure: systolic 90-140 mmHg; diastolic 50-90 mmHg, heart rate 40-120 beats per minute 7. An electrocardiogram (ECG) which, according to the Investigator's judgment does not contraindicate participation in the study. 8. No clinically significant abnormalities in haematology, blood chemistry lab tests at screening. 9. Parents must be able to understand the requirements of the study and must be willing to comply with the requirements of the study Exclusion Criteria: 1. Any medical problem or chronic illness beyond those known to be associated with Rett Syndrome which, in the investigator's judgment, contraindicates administration of the study medication. 2. Severe respiratory dysfunction (defined as tracheostomy and/or chronic oxygen therapy at least 4 hours a day and/or repeated aspiration pneumonia - at least 4 in the last year). 3. Intractable seizures that started during the last 6 months prior to beginning of the study. 4. Known hypersensitivity to glatiramer or mannitol. 5. Participation in another clinical study. 6. Parents of a patient who are unable to communicate well with the investigator and staff and comply with study procedures and follow-up 7. Parents of a patient who are unwilling to sign consent form. | |
| 38 | NCT02030483 | terminated | the company providing one of the study drugs withdrew its support due to low enrollment. therefore, we had to close the study due to lack of funding. | 0.6830639243125916 | phase 1 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['palbociclib', 'dexamethasone', 'lenalidomide'] | ['[Na+].CC([O-])=O', 'C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F', 'NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O'] | Inclusion Criteria: - Subject must voluntarily sign and understand written informed consent. - Subject is ≥18 years at the time of signing the consent form. - Subject has histologically confirmed multiple myeloma that expresses phosphorylated retinoblastoma protein (pRb), as assessed using a historical biopsy sample if available, or a freshly obtained tumor sample. - Subject has relapsed or refractory myeloma as defined by progression of disease either after prior therapy or lack of response to currently used therapy. - Subject must have received and relapsed or progressed after prior treatment with bortezomib. - Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI. - Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement of myeloma - Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin). - Subject is registered into the mandatory Revlimid REMS®program, and is willing and able to comply with the requirements of Revlimid REMS® program. - If subject is a female of childbearing potential (FCBP), she must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. Men must agree to continue birth control for 90 days post-last dose of PD-0332991 - All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program. - Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. - Subject has a life expectancy ≥ 3 months - Subjects must meet the following laboratory parameters: - Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) - Platelet count ≥ 75,000/mm3 (75 x 109/L) - Serum SGOT/AST <3.0 x upper limits of normal (ULN) - Serum SGPT/ALT <3.0 x upper limits of normal (ULN) - Serum creatinine clearance, (either calculated or directly measured). ≥ 60cc/min - Serum total bilirubin <2.0 mg/dL (34 μmol/L) Exclusion Criteria: - Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning). - Subject has a prior history of other malignancies unless disease free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels. - Subject has had myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. - Female subject who is pregnant or lactating. - Subject has known HIV infection - Subject has known active hepatitis B or hepatitis C infection. - Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program. - Subject has known hypersensitivity to dexamethasone or lenalidomide. - Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment. - Subject has any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent. - Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. |
| 39 | NCT02034071 | completed | 0.8218084573745728 | phase 1/phase 2 | ['prader-willi syndrome'] | ["['Q87.11']"] | ['dccr', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Children. adolescents and young adults with genetically confirmed Prader-Willi syndrome - Ages at ≥ 10 years and ≤ 22 years - Generally healthy as documented by the medical history, physical examination, vital sign assessments, 12-lead electrocardiogram (ECG), and clinical laboratory assessments - BMI exceeds the 95th percentile of the age specific BMI value on the CDC BMI charts - Fasting glucose ≤ 126 mg/dL - HbA1c ≤ 6.5 % Exclusion Criteria: - Administration of investigational drugs within 1 month prior to Screening Visit - Anticipated requirement for use of prohibited medications - History of allergic reaction or significant intolerance to: diazoxide, thiazides or sulfonamides - Anticipate transitions in their care from family home to group home or other similar potentially disruptive changes - Congestive heart failure or known compromised cardiac reserve - Any other clinically significant endocrine, cardiovascular, pulmonary, neurological, psychiatric, hepatic, gastrointestinal, hematological, renal, or dermatological disease interfering with the assessments of the investigational drug, according to the Investigator | |
| 40 | NCT02034292 | terminated | sponsor decision | 0.756074070930481 | phase 1 | ['acute coronary syndrome'] | ["['I24.0']"] | ['clopidogrel', 'aspirin', 'apd791', 'placebo'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'CC(=O)OC1=CC=CC=C1C(O)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. a healthy adult between 20 and 45 years old at the time of visit for screening 2. a person who is able to give written consent 3. a person between 50 and 85 kg at the time of visit for screening 4. a woman who is negative on a serum hCG test at the time of visit and the day before a trial, and who is not nursing 5. a woman who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, or who had a contraceptive operation no later than 120 days before visit for screening, or who is menopausal 6. a man who had a contraceptive operation no later than 120 days before visit for screening, or who agrees on double contraception, medically approved, from the time of visit for screening to 90 days after the last administration of a clinical trial drug, and also agree not to donate sperm 7. a person more than hemoglobin 12 g/dL at the time of screening (a woman more than hemoglobin 11 g/dL) 8. a person whose vital signs were in the normal range at the time of visit for screening, or who is medically determined not to be clinically significant by an investigator 9. a person who voluntarily decides to participate in this clinical trial and gives written consent on strict clinical trial compliance 10. a person whose blood can be collected during a study period with visit for monitoring Exclusion Criteria: 1. a person with the medical history of gastric ulcer, duodenal ulcer or esophageal ulcer within 90 days from the time of visit for screening 2. a person with the medical history of gastrointestinal diseases(e.g. Crohn's disease, ulcerative colitis, etc.) or surgery(excluding uncomplicated appendectomy or herniotomy) affecting the absorption of a clinical trial drug 3. a person with the medical history of blood coagulation disorder or hemorrhagic diseases, or with clinically significant abnormal findings decided by a investigator on blood coagulation test at the time of screening 4. a woman with the medical history of dysfunctional uterine bleeding within a year from the time of visit for screening 5. a person with the medical history of epilepsy or convulsion 6. a person with the medical history of internal organ transplant 7. a person expected to be hard to complete a clinical trial because of surgery or medical procedures planned within a clinical trial period 8. a person with the medical history of clinically significant new diseases within 30 days from the time of visit for screening according to investigator's decision 9. a person with hypersensitivity reaction to a drug or gelatin, or the medical history of clinically significant hypersensitivity reaction 10. a person with the history of drug abuse, or with a positive reaction to a drug possible to be abused on urine drug screening 11. a person with the medical history of alcohol abuse within two years from the time of visit for screening 12. a person who is a smoker, or with a positive reaction on a urine nicotine test conducted at the time of visit for screening 13. a person who donated whole blood within 60 days or constituents of blood within 30 days, or received a blood transfusion within 30 days from the time of visit for screening 14. a person taking other clinical trial drugs within 90 days from the time of visit for screening 15. a person taking a prescription drug within 30 days, or a contraindicated drug or oriental medicine within 14 days from the time of visit for screening 16. a person with a positive reaction to a serum test(hepatitis B test, hepatitis C test, HIV test, syphilis test) 17. a person with hepatic enzymes(AST, ALT) more than 2.5 times of the reference upper limit(UNL) or total bilirubin more than 1.5 times of the reference upper limit(UNL) or creatinine more than 1.25 times of the reference upper limit(UNL) 18. a person expected to be hard to complete a clinical trial due to physical or mental status according to investigator's medical decision at the time of visit for screening 19. a person decided to be inappropriate to participate in this clinical trial according to investigator's medical decision on the result of laboratory tests, such as complete blood cell count, general chemical test, clinicochemical urinalysis, and physical examination, vital signs, ECG, other tests excluding exclusion criteria 17 items conducted before subject selection for a clinical trial |
| 41 | NCT02037165 | completed | 0.6575191020965576 | phase 1 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['placebo to bi 1026706', 'pregabalin', 'bi 1026706', 'celecoxib'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'NCC1(CC(O)=O)CCCCC1', 'COC1=CC=C(C=C1)C(=O)CC(=O)C1=CC=C(C=C1)C(C)(C)C'] | Inclusion criteria: 1. Healthy males according to the investigator's assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (Blood Pressure, Pulse Rate), 12-lead electrocardiogram, and clinical laboratory 2. Age 18 to 55 years (incl.) 3. BMI (Body Mass Index) 18.5 to 29.9 kg/m2 (incl.) 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation Exclusion criteria: 1. Any finding in the medical examination (including Blood Pressure, Pulse Rate or Electrocardiogram) deviating from normal and judged clinically relevant by the investigator 2. Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg 3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance 4. Any evidence of a concomitant disease judged clinically relevant by the investigator 5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 6. Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s) 7. Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders | |
| 42 | NCT02037230 | completed | 0.4434145987033844 | phase 1/phase 2 | ['adenocarcinoma of the pancreas'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['mk-1775', 'gemcitabine'] | ['CN1CCN(CC1)C1=CC=C(NC2=NC=C3C(=O)N(CC=C)N(C3=N2)C2=NC(=CC=C2)C(C)(C)O)C=C1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Patients must have pathologically confirmed adenocarcinoma of the pancreas. - Patients will have unresectable disease, defined radiographically as >180 degrees involvement of the superior mesenteric artery or celiac trunk or SMV/portal vein impingement that cannot be surgically reconstructed, in the absence of distant metastasis.. - Patients must have a Zubrod performance status (measure of general well being that ranges from 0 to 5 where 0 represents perfect health) of < 2. - Patients must have adequate organ function defined as follows: absolute neutrophil count of ≥ 1500/mm3, platelets ≥ 100,000/mm3, serum creatinine ≤ 2 mg/dl, total bilirubin ≤ 3, (with relief of biliary obstruction if present (PTC tube or endobiliary stent)) and AST < 5 times the upper limit of normal. - Patients of reproductive potential must agree to use an effective contraceptive method during participation in this trial and for 6 months after the trial. Patients must not be breastfeeding. - Patients must be aware of the investigational nature of the therapy and provide written informed consent. - Patients must be at least 18 years old. Exclusion Criteria: - Other serious uncontrolled concomitant systemic disorders or psychiatric condition that would interfere with the safe delivery of protocol therapy. - A history of previous chemotherapy for pancreatic cancer or abdominal radiation therapy. - The use of any investigational agent in the month before enrollment into the study. - Inability to discontinue a prescription or non-prescription drugs or other products known to be metabolized by CYP3A4, or to inhibit or induce CYP3A4 prior to Day 1 of dosing and to withhold throughout the study until 2 weeks after the last dose of study medication. Medications of particular concern are the following inhibitors of CYP3A4: azole antifungals (ketoconazole itraconazole, fluconazole and voriconazole), macrolide antibiotics (erythromycin, clarithromycin), cimetidine, aprepitant, HIV protease inhibitors, nefazodone and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin. Substrates of CYP3A4 include statins (lovastatin, simvastatin), midazolam, terfenadine, astemizole, and cisapride. | |
| 43 | NCT02040870 | completed | 0.38076862692832947 | phase 1/phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['ldk378'] | ['CC(C)OC1=C(NC2=NC=C(Cl)C(N2)=NC2=CC=CC=C2S(=O)(=O)C(C)C)C=C(C)C(=C1)C1CCNCC1'] | Inclusion criteria: - Histologically or cytologically confirmed diagnosis of NSCLC that carries an ALK rearrangement defined as positive using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria) or positive as assessed by the CFDA approved immunohistochemistry (IHC) test (Ventana Medical Systems, Inc) - Age 18 years or older at the time of informed consent. - Patients must have stage IIIB or IV NSCLC at the time of study entry and have had progressive disease during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. If treated with chemotherapy, maximum 2 lines are allowed. Exclusion Criteria: - Patients with known hypersensitivity to any of the excipients of LDK378 - Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms - History of carcinomatous meningitis - Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. - clinically significant, uncontrolled heart disease. | |
| 44 | NCT02041481 | completed | 0.527278482913971 | phase 1 | ['recurrent colon cancer', 'recurrent rectal cancer', 'stage iva colon cancer', 'stage iva rectal cancer', 'stage ivb colon cancer', 'stage ivb rectal cancer'] | ["['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['mek inhibitor mek162', 'leucovorin calcium', 'fluorouracil', 'oxaliplatin'] | ['CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO', 'NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)N2C=O)N1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Patients with pathologically confirmed colon or rectal cancer who have received and progressed or failed following a fluoropyrimidine, irinotecan, and oxaliplatin based chemotherapy regimens will be eligible for this study; patients who have a known Kirsten rat sarcoma viral oncogene homolog (KRAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild type tumor should have progressed or failed following cetuximab or panitumumab based chemotherapy; prior bevacizumab or regorafenib exposure is not mandated on this study as some patients are deemed poor candidates for anti-angiogenesis therapy and never receive these agents - Patients should have measurable disease defined as a minimum of one tumor measuring >= 10 mm on computed tomography (CT) scans - Signed written informed consent - Absolute neutrophil count (ANC) >= 1.5 x 10^9/L - Hemoglobin (Hgb) >= 9 g/dL without transfusions - Platelets (PLT) >= 100 x 10^9/L without transfusions - Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 × upper limit of normal (ULN); patient with liver metastases =< 5 ×ULN - Total bilirubin =< ULN - Creatinine =< 1.5 mg/dL - Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram - Corrected QT (QTc) interval =< 480 ms - Able to take oral medications - Patient is deemed by the investigator to have the initiative and means to be compliant with the protocol (treatment and follow-up) - Negative serum beta-human chorionic gonadotropin (HCG) test (female patient of childbearing potential only) performed locally within 72 hrs prior to first dose - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 Exclusion Criteria: - History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) - Patients who have had chemotherapy, biologic, targeted, or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from grade 2 and above adverse events due to agents administered more than 4 weeks earlier (with the exception of alopecia or neuropathy) - History of retinal degenerative disease - History of Gilbert's syndrome - Previous or concurrent malignancy with the following exceptions: - Adequately treated skin basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry) - In situ carcinoma of the cervix, treated curatively and without evidence of recurrence - A primary malignancy which has been completely resected and in complete remission for >= 1 years - Prior therapy with a MEK- inhibitor - History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting [CABG], coronary angioplasty, or stenting) < 6 months prior to screening - Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following: symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia - Uncontrolled arterial hypertension despite appropriate medical therapy (defined as systolic blood pressure > 160 or diastolic blood pressure > 100) - Known positive serology for human immunodeficiency virus (HIV), active hepatitis B, and/or active hepatitis C infection - Patients who have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment; NB: muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment - Impairment of gastrointestinal function or gastrointestinal disease (e.g., active ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) - Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc. - Patients who have undergone major surgery =< 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure - Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test - Women of child-bearing potential unless they are using highly effective methods of contraception throughout the study and for 60 days after study drug discontinuation - Sexually active males unless they use a condom during intercourse while taking the drug and for 60 days after stopping treatment and should not father a child in this period; a condom is required to be used also by vasectomized men - Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study - Current grade 3 or higher neuropathy - Use of other investigational drugs - Known hypersensitivity to any components of the study drugs - Prior intolerance to fluorouracil (5-FU) or oxaliplatin, excluding severe neuropathy that reversed to grade 2 or less | |
| 45 | NCT02043860 | terminated | low accrual | 0.6752150654792786 | phase 1 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['melphalan', 'filgrastim (g-csf)'] | ['N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: 1. Patients meeting criteria for symptomatic myeloma 2. Patients must be high or intermediate risk of disease progression as defined by having one of the following criteria: 2.1 ISS stage 2 or 3 disease 2.2 Abnormal metaphase cytogenetics 2.3 Presence of FISH abnormalities aside from hyperdiploidy 3. Patients who have received at least 2 cycles of systemic treatment of any kind in the preceding 12 months 4. Patient age 18-75 years at time of enrollment 5. Karnofsky performance status of ≥70 6. Cardiac function: LVEF >40% 7. Hepatic: Bilirubin <2x upper limit of normal and ALT and AST < 2.5x the upper limit of normal 8. Renal: Creatinine clearance of ≥30mL/min, estimated or calculated 9. Pulmonary: DLCO, FEV1, FVC >50% of predicted (after correction for hemoglobin) Exclusion Criteria: 1. Patients with diagnosis of plasma cell leukemia 2. Patients with myeloma who have had any disease progression prior to enrollment 3. Patients with truly non secretory myeloma (patients with light chain disease are eligible) 4. Pregnant or breast-feeding 5. Uncontrolled viral, fungal or bacterial infection Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis. 6. Patients who have undergone prior allograft or autologous transplant 7. Prior solid organ transplant 8. Patients receiving prior radiation to more than 20% of bone marrow containing areas |
| 46 | NCT02044796 | completed | 0.5080364346504211 | phase 1/phase 2 | ['acute biphenotypic leukemia', 'de novo myelodysplastic syndrome', 'previously treated myelodysplastic syndrome', 'recurrent adult acute myeloid leukemia', 'untreated adult acute myeloid leukemia', 'secondary acute myeloid leukemia'] | ["['D46.Z', 'D46.9', 'C94.6', 'D46.C']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['D75.1', 'E26.1', 'N91.1', 'N91.4', 'N94.5', 'A51.41', 'A51.43']"] | ['cladribine', 'cytarabine', 'mitoxantrone hydrochloride'] | ['[Mg++].[Cl-].[Cl-]', 'ClCCN(CCCl)P1(=O)NCCCO1', 'OCCNCCNC1=CC=C(NCCNCCO)C2=C1C(=O)C1=C(C(O)=CC=C1O)C2=O'] | Inclusion Criteria: - For patients with newly diagnosed disease: diagnosis of "high-risk" myelodysplastic syndrome (MDS) (>= 10% blasts) or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification; for patients with relapsed/refractory disease: prior diagnosis of "high-risk" MDS or non-APL AML, with relapsed/refractory disease according to standard criteria requiring first or subsequent salvage therapy; patients with biphenotypic AML are eligible - Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution; flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines - For patients with relapsed/refractory disease: patients with prior autologous or allogeneic hematopoietic cell transplantation (HCT) for MDS/AML are eligible if relapse occurs provided symptoms of graft-versus host disease are well controlled with stable use of immunosuppressive agents - Treatment-related mortality (TRM) score =< 6.9 as calculated with simplified model - The use of hydroxyurea prior to study registration is allowed; patients with symptoms/signs of hyperleukocytosis or white blood cell (WBC) > 100,000/uL can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2/dose) prior to enrollment - For patients with relapsed/refractory disease: patients may have previously received chemotherapy with a mitoxantrone- or cladribine-based regimen for MDS or AML; if that patient has received G-CLAM before and has been sensitive to this regimen, eligibility will be determined on a case-by-case basis by the study principal investigator (PI) - Should be off any active systemic therapy for AML with the exception of hydroxyurea for at least 14 days prior to study registration unless patient has rapidly progressive disease, and all grade 2-4 non-hematologic toxicities should have resolved - Bilirubin =< 2.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 14 days prior to study day 0) - Serum creatinine =< 2.0 mg/dL (assessed within 14 days prior to study day 0) - Left ventricular ejection fraction >= 45%, assessed within 3 months prior to study day 0, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure; if the patient had anthracycline-based therapy since the most recent cardiac assessment, cardiac evaluation should be repeated if there is clinical or radiographic suspicion of cardiac dysfunction, or if the previous cardiac assessment was abnormal - Women of childbearing potential and men must agree to use adequate contraception - Provide written informed consent Exclusion Criteria: - Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for tyrosine kinase inhibitor treatment - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)]); patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours; patients with fever thought to be likely secondary to leukemia are eligible - Known hypersensitivity to any study drug - Pregnancy or lactation - Treatment with any other investigational agent | |
| 47 | NCT02047149 | terminated | low accrual | 0.5435289144515991 | phase 1 | ['chronic myelogenous leukemia'] | ["['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']"] | ['zileuton (zyflo®) dasatinib (sprycel®)', 'dosing with zileuton/dasatinib in cml', 'daily dosing of zileuton/dasatinib', 'daily dosing with zileuton/dasatinib for cml'] | ['CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1'] | Inclusion Criteria: Target Population: 1. Patients with CML with known inadequate response (as appropriate for their CML status) to TKIs or known resistance will be considered for this study - Patients who are resistant or not responding adequately to dasatinib as a first line therapy, but are not able or eligible to receive other effective second line treatment can be considered for participation in the study. - Age > 18 years - ECOG performance status ≤ 2 - Total bilirubin < 2.0 times the institutional Upper Limit of Normal (ULN) - Hepatic enzymes (AST, ALT ) ≤ 1.5 times the institutional ULN - Serum Na, K+, Mg2+, Phosphate and Ca2+>= Lower Limit of Normal (LLN) - Serum Creatinine < 2.3 mg/dL - PT, PTT all Grade 0-1 3) Ability to take oral medication 4) Concomitant Medications - Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy 5) Age and Sex - Women of childbearing potential and men of fathering potential must use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy Exclusion Criteria: 1. Sex and Reproductive Status - Women of childbearing potential and men of fathering potential unable or unwilling to use an adequate method of contraception to avoid pregnancy throughout the study to minimize the risk of pregnancy 2. Target Population - Patients intolerant of dasatinib. 3. Medical History and Concurrent Diseases - History of active malignancy during the past 5 years with the exception of nonmetastatic treated skin cancer (e.g. basal or squamous cell carcinoma ) or stage 0 cervical carcinoma - Patients known to be HIV-positive - Patients with active, uncontrolled infections - Concurrent medical condition which may increase the risk of toxicity, including: - Pleural or pericardial effusion of any grade - Cardiac Conditions: - Uncontrolled angina, congestive heart failure or MI within (6 months) - Diagnosed congenital long QT syndrome - Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) - Prolonged QTc interval on pre-entry electrocardiogram (> 450 msec) - Severe cardiac dysfunction (NYHA classification III-IV) - Severe pulmonary disease - History of significant bleeding disorder unrelated to cancer 4. Physical and Laboratory Test Findings - Hepatic dysfunction (serum bilirubin ≥ 2 x ULN, and/or ALT ≥ 3 x ULN, and/or AST ≥ 3 x ULN) - Renal dysfunction (creatinine ≥ 200 μmol/l or 2.3 mg/dl) - Subjects with hypokalemia or hypomagnesemia that cannot be corrected prior to dasatinib administration 5. Allergies and Adverse Drug Reactions - Patients with known allergic reaction or intolerance to either dasatinib or zileuton 6. Prohibited Treatments and/or Therapies - Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: - quinidine, procainamide, disopyramide - amiodarone, sotalol, ibutilide, dofetilide - erythromycin, clarithromycin - chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide - cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine. - Patients requiring anticoagulation with Coumadin 7. Other Exclusion Criteria - Prisoners or subjects who are involuntarily incarcerated. - Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness. |
| 48 | NCT02049385 | terminated | severe side effects & lack of target engagement | 0.6836397647857666 | phase 1/phase 2 | ['depression'] | ["['F32.A', 'F53.0', 'P91.4', 'Z13.31', 'Z13.32']"] | ['diazoxide', 'placebo'] | ['CC1=NS(=O)(=O)C2=C(N1)C=CC(Cl)=C2', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | - INCLUSION CRITERIA: - 18 to 65 years of age. - Women of child bearing potential must have a negative serum pregnancy test and confirmed (by the investigator) use of two effective methods of contraception (see below). - Each subject must be capable of understanding all required tests and examinations and must sign an informed consent document. - Subjects must fulfill DSM-IV criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Subjects must be experiencing a current major depressive episode of at least four weeks duration. - Subjects must have an initial score of at least 20 on the MADRS at screening and at baseline of study Phase I. - Subjects must have a current or past history of lack of response to two adequate antidepressant trials (may be from the same chemical class) operationally defined using the modified-Antidepressant Treatment History Form (ATHF). EXCLUSION CRITERIA: - Current psychotic features or a current or past diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV. - Subjects with a history of DSM-IV drug or alcohol dependency or abuse (except for caffeine or nicotine dependence) within the preceding three months. - Head injury that results in loss of consciousness exceeding five minutes (for the imaging component of the study). - Subjects with a DSM IV Axis II diagnosis of borderline or antisocial personality disorder. - Pregnant or nursing women or women of child bearing potential not using two medically accepted means of contraception (including oral, injectable, or implant birth control, condoms, a diaphragm with spermicide; intrauterine devices (IUD); tubal ligation; abstinence; or partner with vasectomy). - Serious, unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. - Subjects with hyperthyroidism or clinical hypothyroidism. - Subjects with one or more seizures without a clear and resolved etiology. - Clinically significant abnormal laboratory tests (including blood glucose). - Diabetes - Fasting plasma glucose concentration >120 mg/dl - Upright diastolic blood pressure <60mmHg on three occasions 30 minutes apart (based on scheduled research measurements). - Treatment with a reversible MAOI within four weeks of study Phase II. - Treatment with fluoxetine within five weeks of study Phase II. - Treatment with any other disallowed concomitant medication 14 days before randomization. - Treatment with clozapine or ECT within one month of randomization. - Lifetime history of deep brain stimulation. - Subjects who, in the investigator's judgment, pose a current serious suicidal or homicidal risk. - Positive HIV test - Contraindications to MRI (metal in body, claustrophobia, etc) No structured psychotherapy will be permitted during the study. Definition of treatment-resistance All subjects are required to have previously failed to respond to two adequate antidepressant trials (may be from the same chemical class). Adequacy of antidepressant trials will be determined via the clinician administered modified ATHF. |
| 49 | NCT02050815 | terminated | the sponsor is terminating the study because the primary objective was achieved after 5 of the 6 subjects were assessed in the final cohort. | 0.4755485951900482 | phase 1 | ['hepatic impairment'] | ["['Z73.82', 'G31.84', 'M10.38', 'M10.30', 'M10.311', 'M10.312', 'M10.319']"] | ['mek162'] | ['CN1C=NC2=C(F)C(NC3=CC=C(Br)C=C3F)=C(C=C12)C(=O)NOCCO'] | Inclusion Criteria: - Written informed consent prior to any screening procedures - Male or female (postmenopausal or sterilized) - Subject body weight at least 45 kg and a body mass index (BMI) in the range of 18 to 35.0 kg/m2 - Subjects with normal hepatic function must have total bilirubin ≤ upper limit of normal (≤ ULN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) ≤ ULN, serum creatinine ≤ ULN, serum amylase and lipase ≤ ULN Additional inclusion criteria for subjects with abnormal liver function determined by elevation of serum total bilirubin are: - Absolute neutrophil count (ANC) > 1000 cell/mm3 - Hb > 9 mg/dl, - Platelet count > 30,000/mm3 - Serum creatinine ≤ 1.8 mg/dl - Otherwise considered healthy and free of significant medical disorders unrelated to the subject's hepatic disorder Exclusion Criteria: - Women of child-bearing potential - Pregnant or nursing (lactating) women - Subjects with impaired cardiovascular function or clinically significant cardiovascular diseases - Uncontrolled arterial hypertension despite medical treatment - History or current evidence of retinal vein occlusion (RVO) or current risk factors of RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes), - History of Gilbert's syndrome - Immuno-compromised subjects (including known history/seropositivity of HIV) - Any surgical or medical condition (other than hepatic impairment) or receiving any pharmacological treatment which might significantly alter the absorption or metabolism of drugs or which may jeopardize the subject in case of participation in the study - Antecedent of malignancy with the following exceptions: adequately treated basal cell or squamous cell carcinoma of the skin - Subjects who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Subjects who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure - History of clinically significant drug allergy - Prior therapy with a MEK-inhibitor - Use of an investigational drug within 30 days of screening - Current smoker or has used tobacco products or products containing nicotine within 7 days prior to dosing of study drug - Consumption of alcohol within 3 days prior to dosing or during the study Additional exclusion criteria for subjects with normal hepatic function: - Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as ALT, AST, GGT, alkaline phosphatase, or serum bilirubin. ALT and AST beyond the normal range before inclusion Presence of impaired renal function as indicated by abnormal creatinine (creatinine clearance < 80 mL/min) values and/or serum creatinine ≥1.8 mg/dL- A positive Hepatitis B or Hepatitis C test result Additional exclusion criteria for subjects with elevation of serum bilirubin > UNL: - Symptoms or history of encephalopathy (Grade II or worse) within 4 weeks of study entry - Clinical evidence of severe ascites requiring intervention - International normalized ratio (INR) >2.5 - Any evidence of progressive liver disease within the last 3 weeks prior to the screening visit) as indicated by worsening of clinical manifestations (i.e.: ascites, encephalopathy) and/or laboratories abnormalities (liver transaminases, alkaline phosphatase and GGT or a ≥ 50% worsening of serum bilirubin or prothrombin time) - History of surgical portosystemic shunt with complications (i.e. hepatic encephalopathy, heart failure) - Active bleeding during the last 28 days prior to dosing including variceal bleeding |
| 50 | NCT02052739 | completed | 0.6234543323516846 | phase 1/phase 2 | ['super-refractory status epilepticus'] | ["['G40.803', 'G40.804', 'G40.823', 'G40.824', 'G40.833', 'G40.834', 'G40.911']"] | ['sage-547'] | ['[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)C(C)=O'] | Inclusion Criteria: - Subjects 2 years of age and older. - Subjects with an EEG-confirmed SRSE diagnosis under concomitant therapy with a continuous IV AED (third-line agent) for ≥ 24 hours. For this study, SRSE is defined by the following criteria and in accordance with those used at major epilepsy treatment centers: - Failure to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial AED treatment), according to institution standard of care, and - Failure to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED) according to institution standard of care, and - Presence of one or more breakthrough seizures > 6 hours after initiation of the continuous IV AED/third-line agent (e.g., pentobarbital, midazolam, propofol) Exclusion Criteria: - Subjects with SRSE due to anoxic/hypoxic encephalopathy, children (subjects aged less than 18 years) with an encephalopathy due to an underlying progressive neurological disorder. - Subjects with clinically significant electrocardiogram (ECG) abnormalities. - Subjects with a significant medical or surgical condition that may compromise vital organ systems, or other conditions that would place the subject at increased risk such as dialysis or acute respiratory distress syndrome, severe cardiogenic or vasodilatory shock requiring 2 or more pressors, fulminant hepatic failure, etc. - Subjects who are receiving a continuous IV AED (third-line agent) for seizure suppression or burst-suppression that will require greater than 24 hours to wean. | |
| 51 | NCT02054442 | active, not recruiting | 0.4779614508152008 | phase 1/phase 2 | ['squamous cell carcinoma of the head and neck'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['cetuximab', 'methotrexate'] | ['[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CSC(N)=N1)C(O)=O', 'CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O'] | Inclusion Criteria: - Cytologically/histologically-proven SCCHN - Recurrent or metastatic SCCHN - At least one measurable lesion as determined by RECIST v1.1 is required. Lesions in previously irradiated areas should not be considered measurable unless there is clear evidence of progression in such lesions since the radiotherapy. - No prior systemic treatment for recurrent or metastatic disease - Primary site: (1) oral cavity, (2) oropharynx, (3) hypopharynx, (4) larynx, or (5) unknown primary squamous cell carcinoma in the head and neck region presenting originally with lymph node metastases (N1-N3). - Time between prior treatment and inclusion in the study (> 3 months). Palliative RT in case of painful bone metastases is allowed in phase II and after 4 weeks in phase Ib - Ineligible (due to medical co-morbidities) or intolerant to platinum-based therapy per medical history or refusing cisplatin-based chemotherapy by the patient - WHO performance status 0-2. - Age >18 years - Adequate organ function and laboratory parameters as defined by: - Absolute neutrophil count (ANC) ≥ 1.5 x 109 /L - Hemoglobin (Hb) ≥ 9 g/dl 5.6 mmol/l (which may be achieved by transfusion) - Platelets (PLT) ≥ 100 x 109/L - AST and ALT ≤ 2.5 x ULN (upper limit of normal) - Serum bilirubin ≤ 1.5 x ULN - Calculated creatinine clearance or MDRD > 60ml/min - Recovered from all adverse events (AEs) of previous anti-cancer therapies. AEs related to prior radiotherapy are allowed. - Written informed consent Exclusion Criteria: - Serious active infections - Patients (M/F) with reproductive potential not implementing adequate contraceptives measures - Prior treatment with EGFR inhibitors or MTX - Concomitant (or within 4 weeks before randomization) administration of any other experimental drug under investigation - Concurrent treatment with any other anti-cancer therapy. - Central nervous system involvement - Lung fibrosis - Pleural effusion or ascites or other third space effusions - History of another malignancy within 2 years prior to starting study treatment, except cured basal cell carcinoma of the skin, excised carcinoma in situ of the cervix, or other head and neck cancer. - Pregnancy or lactation - Any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, social/psychological complications. | |
| 52 | NCT02055690 | terminated | safety | 0.5698805451393127 | phase 1/phase 2 | ['ovarian neoplasms', 'neoplasms, ovarian', 'ovarian cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['pazopanib', 'fosbretabulin'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'COC1=CC=C(C[C@@H](O)C2=CC(OC)=C(OC)C(OC)=C2)C=C1O'] | Inclusion Criteria: - Advanced, progressive, recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma, which has recurred following at least one platinum-containing regimen. - Progressive disease according to RECIST 1.1 or GCIG criteria within 3-12 months of completing platinum containing therapy, although this need not be the immediately preceding regimen. - World Health Organisation (WHO) performance status of 0 or 1 (Appendix 1). - Measurable disease (RECIST 1.1 (Appendix 2) or Progressive Disease (PD) according to CA125 GCIG criteria with non-measurable disease on CT scan. - Life expectancy of at least 12 weeks. - Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day 1) before the patient receives the first dose of Investigational Medicinal Product (IMP): - Haemoglobin (Hb) ≥ 90 g/L - Absolute neutrophil count ≥ 1.5 x 109/L - Platelet count ≥ 100 x 109/L - Serum potassium within normal range - Bilirubin ≤ 1.5 x upper limit of normal (ULN) - Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 2.5 x ULN unless raised due to hepatic metastatic disease in which case up to 5 x ULN is permissible - Either: Calculated creatinine clearance ≥ 40 mL/min (uncorrected value) Or: Isotope clearance measurement ≥ 40 mL/min (corrected) - Activated partial thromboplastin time (aPTT) ≤ 1.2 x ULN - Prothrombin Time (PT) or International normalised ratio (INR) ≤ 1.3 x ULN - Urine protein dipstick of less than or equal to 2+, or if 2+ or greater the patient must have a 24 hour urinary protein value of less than 2 g. - Clinically euthyroid. - Aged 18 years or over at the time of consent. - Written (signed and dated) informed consent and capable of co-operating with treatment and follow-up. - Patients can have received bevacizumab prior to trial entry providing that the last dose was administered at least 6 months before the first dose of IMP. Exclusion Criteria: - Radiotherapy, surgery or tumour embolisation within 28 days before the first dose of IMP - Endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C and six weeks for investigational medicinal products) before the first dose of IMP. - Ongoing grade ≥ 2 toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Chief and Principal Investigators should not exclude the patient; and grade 1 or 2 neurotoxicity considered to be due to paclitaxel. - Female patients who are able to become pregnant (or are already pregnant or lactating). Those who have a negative serum or urine pregnancy test before enrolment and agree to use two highly effective forms of contraception (oral, injected or implanted hormonal contraception and condom, have an intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible. - Major thoracic or abdominal surgery from which the patient has not yet recovered. - At high medical risk because of non-malignant systemic disease including active uncontrolled infection. - Known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV). - History of any of the following cardiovascular conditions within the last six months: - Coronary revascularisation (percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)) - Acute coronary syndrome (myocardial infarction (MI), unstable angina) - Symptomatic peripheral vascular disease - Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (Appendix 4) - Patients who have sustained hypertension, defined as a systolic blood pressure (SBP) of > 140 mm Hg or diastolic blood pressure (DBP) of > 90 mm Hg, on three occasions. - ECG with evidence of clinically significant abnormalities. - Patients with a QTc> 480ms or taking any drug known to prolong the QTc interval that cannot be stopped for the duration of the trial (Appendix 4). - Patients with pathologic bradycardia (<60 b/m in non-athletes), heart block (excluding first-degree block, being PR interval prolongation only). - History of cerebrovascular accident (including transient ischaemic attack (TIA)), pulmonary embolism or untreated deep vein thrombosis (DVT) within the past six months. Patients with recent DVT or pulmonary embolism who have been treated with therapeutic anti-coagulant agents for at least six weeks will be eligible, provided their INR (if taking oral anti-coagulants) has been stable for this period of time. - History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic and have had no requirement for steroids or anti-convulsant medication for six months prior to the first dose of IMP. - Clinically significant abnormalities that may increase the risk of gastrointestinal bleeding or perforation, including but not limited to: - Bleeding: Active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, Inflammatory bowel disease (Crohn's disease, ulcerative colitis); - Perforation: History of abdominal fistula or large pelvic mass; gastrointestinal perforation or intra-abdominal abscess within four weeks prior to first dose of IMP; previous bowel surgery which is judged by the investigator to increase significantly the risk of gastrointestinal complications from trial treatment - Evidence of active bleeding or bleeding diathesis. - Transfusion within one week prior to first dose of IMP. - Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels. - Clinically significant haemoptysis, within eight weeks before the first dose of IMP. - Previous treatment with pazopanib. - Any participant that is participating in (or plans to participate in) another interventional clinical trial, whilst taking part in this Phase Ib/II study of fosbretabulin and pazopanib. Participation in an observational trial would be acceptable. - Any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial. - Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin and no evidence of recurrence of other malignancy for at least 2 years. - Hypersensitivity to Pazopanib or any of it's excipients |
| 53 | NCT02055924 | terminated | ansm decision due to veino occlusive disease (security alert) | 0.6771156191825867 | phase 1 | ['b-cell lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['ibrutinib and immunochemotherapies'] | ['NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1'] | Inclusion Criteria: 1. Patients with any type of relapsed or refractory B-cell lymphoma will be eligible in groups A, A bis, B and B bis (during the dose escalation and the expansion parts of the study) and untreated patients with mantle cell lymphoma will be eligible for group C (only during the expansion part of the study) 2. Each patient (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study 3. Patients eligible for autologous stem cell transplantation (ASCT) for whom R-DHAP or R-DHAOx is an acceptable therapy regarding the investigator's opinion 4. Measurable disease defined by at least one single node or tumor lesion > 1.5 cm 5. Patients who received prior therapy with at least one but no more than two lines therapies for B-Cell Lymphoma (except for patients included in group C during the expansion part of the study) 6. Aged between 18 years and 70 years (included) 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 8. Any of the following hematology values within 14 days prior to inclusion and prior to the first dose of study drug : 1. Absolute neutrophil count (ANC) > 1,000 cells/mm3 (1.0 x 109/L) unless if bone marrow infiltration from lymphoma 2. Spontaneous Platelets count > 75,000 cells/mm3 (75 x 109/L) within 7 days of any platelet transfusion (allowed up to 50 x 109/L if due to bone marrow infiltration from lymphoma) 9. Patients assessed as being able to receive full doses of R-DHA(P/Ox) for 3 cycles or 4 cycles for patients included in group C of the expansion phase 10. Life expectancy of ≥ 90 days (3 months) 11. Women of childbearing potential* and men who are sexually active must be practicing a highly effective method of birth control during the study and during 12 months after the end of treatments. Men must agree to not donate sperm during the study and during 12 months after the end of treatments 12. Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) or urine pregnancy test at Screening Exclusion Criteria: 1. Previous treatment with a BTK inhibitor 2. Patients who progressed or became refractory while on treatment with a phosphoinositide 3-kinase (PI3K) inhibitors 3. Inability to tolerate 4 courses of high dose ara-C / platin compound, especially if due to underlying comorbidities 4. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug 5. Major surgery, within 4 weeks prior to the first dose of study drug 6. Known bleeding diathesis 7. Condition that requires therapeutic anticoagulation with Vitamin K antagonists 8. Condition that requires treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor 9. Any life-threatening illness, serious medical condition, laboratory abnormality, organ system dysfunction or psychiatric illness which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk and that would prevent the patient from signing the informed consent form 10. Known central nervous system or meningeal involvement by lymphoma 11. Contraindication to any drug contained in these regimen 12. Known history of human immunodeficiency virus (HIV) 13. Known active Hepatitis C Virus (HCV; RNA polymerase chain reaction (PCR)-positive) or active Hepatitis B Virus infection (HBs Ag positive or DNA PCR-positive) or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. Patients with PCR-negative for hepatitis B virus (HBV) are permitted in the study. 14. Left ventricular ejection fraction (LVEF) < 45% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan 15. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification 16. Any of the following biochemical values within 14 days prior to inclusion and prior to the first dose of study drug : 1. Serum glutamic-oxaloacetic transaminase/aspartate aminotransferase (SGOT/ASAT) or serum glutamic-pyruvic transaminase/alanine aminotransferase (SGPT/ALAT) > 3.0 x upper limit of normal (ULN) 2. Serum total bilirubin > 2.0 mg/dL (34 µmol/L), except in patients with hemolytic anemia or with Gilbert syndrome, 3. Calculated creatinine clearance of < 50 mL /min (for patients who will have DHAOx chemotherapy) or < 70 mL/min (for patients who will have DHAP chemotherapy) 17. Patients with pre-existing ≥ Grade 2 neuropathy 18. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been free of the disease for ≥ 3 years 19. Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the first dose of study drug 20. Women who are pregnant or breastfeeding 21. Medical history of hepatic chronic disease whatever the anteriority 22. Sinusoidal obstruction syndrome (Veno-Occlusive Disease (VOD)) whatever the anteriority |
| 54 | NCT02056756 | active, not recruiting | 0.6814257502555847 | phase 1/phase 2 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['carfilzomib'] | ['CC(C)C[C@H](NC(=O)[C@H](CCC1=CC=CC=C1)NC(=O)CN1CCOCC1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1'] | Inclusion Criteria: - Patient ≥ 18 years old. - Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements. - Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. - Female patient is either post-menopausal or surgically sterilized or commits continued abstinence from heterosexual intercourse during the duration of the study or is willing to use two methods of birth control, one highly effective method and one additional effective method at the same time, at least 4 weeks before starting carfilzomib and bendamustine therapy, during carfilzomib and bendamustine therapy and for at least 4 weeks after stopping carfilzomib and bendamustine therapy. Highly effective methods are hormonal contraceptives (birth control pills, injections, and implants), intrauterine device, tubal ligation and partner's vasectomy. Additional effective methods are condom, diaphragm, and cervical cap. Women with child bearing potential must have two negative pregnancy tests (sensitivity at least 50 mIU/mL) prior starting carfilzomib and bendamustine therapy. The first pregnancy test must be performed 10 - 14 days and the second within 24 hours before starting carfilzomib and bendamustine therapy. Pregnancy testing for the first 4 weeks of study therapy must be performed weekly and thereafter every 4 weeks if menstrual cycles are regular or every 2 weeks if menstrual cycles are irregular. - Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study and for 6 months after stopping study therapy. - Patient with relapsed or/and refractory multiple myeloma after failure of two or more treatment regimens (previous bortezomib is allowed). - Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein (M-protein) value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo- or non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of patients admitted to this study will be oligo- or non-secretory MM with free light chains only in order to maximize interpretation of benefit results. - Patient has a Karnofsky performance status ≥60%. - Patient has a life expectancy >6 months. - Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration): - Platelet count ≥70 x 109/L (≥50 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration). - Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors. - Corrected serum calcium ≤14 mg/dL (3.5 mmol/L). - Alanine transaminase (ALT): ≤ 3 x the ULN. - Total bilirubin: ≤ 2 x the ULN. - Calculated or measured creatinine clearance ≥ 15 mL/min (or, as alternative serum creatinine <2 mg/dL). - LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available (not applicable in Germany). Exclusion Criteria: - Pregnant or lactating females - Patient has active infectious hepatitis type B or C or HIV. - Patients with active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. - Peripheral neuropathy (PN) > CTCAE grade 2 and ≥ grade 2 painful PN (with the difference being in the exclusion of patients with Grade 2 painful PN). - Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib) - Known history of intolerability to high dose dexamethasone - Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and anti-platelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment. - Subject with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to baseline; - Patient has any other clinically significant illness that would, in the investigator's opinion, increase the patient's risk for toxicity. - Patient with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma of the skin, or in situ cancer of the cervix or breast, or localized prostate cancer of Gleason score <7 with a stable PSA). | |
| 55 | NCT02057770 | terminated | low accrual rate | 0.6483319997787476 | phase 1 | ['leukemia, myeloid, acute'] | ["['C92.A1', 'C92.A2', 'C92.61', 'C92.62', 'C92.A0', 'C92.60']"] | ['busulfan', 'fludarabine phosphate', 'cyclophosphamide', 'tocilizumab'] | ['CS(=O)(=O)OCCCCOS(C)(=O)=O', 'NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O', 'ClCCN(CCCl)P1(=O)NCCCO1'] | Inclusion Criteria: - AML without complete remission (CR/CRc/CRi) after at least 2 induction therapies OR - AML that has relapsed within 6 months after obtaining a CR OR - AML that has relapsed more than 6 months after obtaining a CR, and has treatment failure (TF) or progressive disease (PD) following at least 1 re-induction regimen OR - AML that has relapsed post Allogeneic transplantation - Active AML (bone marrow blasts ≥ 5% by morphology, staining, or flow) and/or presence of estramedullary disease - Available HLA-haploidentical donor that meets the following criteria: - Blood-related family member (sibling (full or half), offspring, or parent, cousin, niece or nephew, aunt or uncle, or grandparent) - At least 18 years of age - HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards - In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC - No active hepatitis - Negative for HTLV and HIV - Not pregnant NOTE: there were HLA-matched sibling and HLA-matched unrelated donor cohorts, but those closed without completion of accrual with Amendment 11 - Karnofsky performance status ≥ 50 % - Adequate organ function as defined below: - Total bilirubin ≤ 2.5 mg/dl (unless the patient has a history of Gilbert's syndrome) - AST(SGOT) and ALT(SGPT) ≤ 3.0 x IULN - Creatinine ≤ 2.0 x IULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula - Oxygen saturation ≥ 90% on room air - LVEF ≥ 40% - FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation. - At least 18 years of age at the time of study registration - Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable) Exclusion Criteria: - Circulating blast count ≥ 10,000/uL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed) - Known HIV or Active hepatitis B or C infection - Known hypersensitivity to one or more of the study agents - Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -7) - Currently receiving or has received any intensive chemotherapy within the 14 days prior to the first dose of study drug (Day -7) (hydrea or other non-intensive regimens such as decitabine may be used but must stop at least one day prior to the first dose of study drug) - Pregnant and/or breastfeeding - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements. |
| 56 | NCT02058407 | terminated | drug related aes observed upon repeat dosing that with longer treatment duration could become worse. required action on some biomarkers not observed. | 0.5597631335258484 | phase 1 | ['bronchiectasis'] | ["['J47.9', 'Q33.4', 'J47.1', 'J47.0']"] | ['gsk2793660 solution', 'gsk2793660 capsule', 'placebo solution', 'placebo capsule'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: - Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, and laboratory tests. A subject with a clinical abnormality or laboratory parameters outside the reference range, and which is not a part of an eligibility criterion, for the population being studied may be included only if the Investigator and GSK medical monitor consider the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures and outcome. - Male or female between 18 and 55 years of age inclusive, at the time of signing the informed consent. - A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, removal of both ovaries or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >21.7 International units per liter (IU/L) and oestradiol <110 picomole per liter (pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. - Male subjects with female partners of child-bearing potential must agree to use one of the approved contraception methods as detailed in the protocol. This criterion must be followed from the time of the first dose of study medication until the follow-up visit. - Body weight >=50 Kilogram (kg) and Body Mass Index (BMI) within the range 19.9-30.0 kg/meter square (m^2) (inclusive). - Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. - Based on averaged QT duration corrected for heart rate by Fridericia's formula (QTcF) values of triplicate ECGs obtained over a brief recording period: Average QTcF <450 milliseconds (msec) - Systolic blood pressure <=130 millimeters of mercury (mmHg) and diastolic blood pressure 80 mmHg based on average values of triplicate blood pressure readings obtained over a brief period. - Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5x Upper Limit of Normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Exclusion Criteria: - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - ECG finding of second or third degree heart block. - History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. - History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. - History of sensitivity to heparin or heparin-induced thrombocytopenia. - A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. - Urinary cotinine or exhaled breath carbon monoxide (CO) levels indicative of current smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. - A positive pre-study drug/alcohol screen. - A positive test for human immunodeficiency virus (HIV) antibody. - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. Blood donation will not exceed 500 mL for the entire study. - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). - Exposure to more than four new chemical entities within 12 months prior to the first dosing day. |
| 57 | NCT02059967 | withdrawn | due to no accrual. | 0.3772428631782532 | phase 1 | ['adenocarcinoma of the lung', 'large cell lung cancer', 'squamous cell lung cancer', 'stage iia non-small cell lung cancer', 'stage iib non-small cell lung cancer', 'stage iiia non-small cell lung cancer', 'stage iiib non-small cell lung cancer'] | ["['D02.20', 'D02.21', 'D02.22']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['paclitaxel', 'carboplatin'] | ['[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: - Histologically-proven (by biopsy or cytology), unresectable or inoperable lung cancer of the following histologic types: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, non-small cell carcinoma not otherwise specified. - The tumor stage must be Stage IIA-IIIB (AJCC 7th edition). See http://aboutcancer.com/AJCC 7th lung 1.gif and http://aboutcancer.com/AJCC 7th lung 2.gif for staging. - All detectable tumor must be encompassed by radiation therapy fields. - 18-fluorodeoxyglucose PET is required for staging and treatment planning. - Atelectasis, if present, must involve less than a complete lung. - Laboratory values: - Neutrophils >1500/µL - Platelets >100,000/µL - Bilirubin < 1.5 mg/dL - Aspartate aminotransferase (AST; formerly serum glutamic oxaloacetic transaminase [SGOT]) < 2x upper limit normal - Alanine aminotransferase (ALT; formerly serum glutamic pyruvic transaminase [SGPT]) < 2x upper limit normal - Serum creatinine < 2.0 mg/dL - Glomerular filtration rate (GFR) calculated (kidney function test) within 30 days must be ≥ 59 mL/min - Pulmonary function test (PFT) with FEV-1 ≥ 1.0 L/sec - Plan of curative radiotherapy with or without concurrent chemotherapy. - Karnofsky Performance Scale score of ≥ 70%. - Age ≥ 18 years old. - Measurable disease on the planning CT. - Patient must have a completed IMRT plan to 66 Gy in 2 Gy fractions with ≥ 95% of the PTV covered by the prescription dose, and the attending physician must have reviewed and approved the DVHs as follows: - total lung V20 Gy ≤ 30% - mean esophageal dose ≤ 34 Gy - esophageal planning organs-at-risk volume (PRV) V60 Gy ≤ 30% - heart V40 Gy ≤ 50% - maximum brachial plexus dose ≤ 66 Gy - maximum spinal cord PRV dose ≤ 50 Gy - maximum aorta dose ≤ 66 Gy - maximum main bronchus dose ≤ 66 Gy - maximum dose ≥ 66 Gy allowed in only one lobar bronchus. - Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: - Complete tumor resection, recurrent disease, or those patients eligible for definitive surgery. - Prior radiation therapy to the thorax. - Previous chemotherapy or previous biologic response modifiers for current lung cancer or within the past 5 years. - Clinically significant pleural effusions, pericardial effusions, or superior vena cava syndrome. - Oxygen supplementation required during therapy. - Involvement of the brachial plexus, or infiltration of the aorta, heart, or esophagus. - Tumors that affect more than one lobar bronchus, except the second involved bronchus in the right middle lobe bronchus. - Unable to perform the BH procedures, unless tumor motion is ≤ 3 mm. - Myocardial infarction within the last 6 months, symptomatic heart disease, uncompensated chronic obstructive pulmonary disease (COPD), or uncontrolled bronchospasms. - History of a prior malignancy from which the patient has not been disease free for a minimum of 2 years, other than adequately treated basal/squamous skin cancer or in situ cervix cancer or other in situ malignancy. - Pregnant or lactating women. |
| 58 | NCT02060253 | completed | 0.5647437572479248 | phase 1 | ['her2-positive breast cancer', 'male breast cancer', 'recurrent breast cancer', 'stage iiia breast cancer', 'stage iiib breast cancer', 'stage iiic breast cancer', 'stage iv breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C50.021', 'C50.022', 'C50.029', 'C50.121', 'C50.122', 'C50.129', 'C50.621']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['ganetespib', 'paclitaxel'] | ['CC(C)C1=CC(C2=NN=C(O)N2C2=CC=C3N(C)C=CC3=C2)=C(O)C=C1O', '[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC'] | Inclusion Criteria: - Pathologically confirmed diagnosis of breast cancer (central confirmation is not required) - Patients must be at least 18 years of age - Metastatic or advanced breast cancer that is evaluable OR metastatic or advanced breast cancer that is measurable for response as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status 0-2 - Life expectancy of at least 3 months as assessed by the investigator - Patients with estrogen receptor (ER)+ breast cancer must have received prior treatment with at least one hormone therapy - Absolute neutrophil count ≥ 1,500 cells/uL - Platelets ≥ 100,000/uL - Hemoglobin ≥ 9.0g/dL - Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN - Albumin ≥ 3.0 g/dL - Adequate renal function as defined by a serum creatinine ≤ 1.5 x ULN - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures - Female subjects of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment - Female subjects of childbearing age must have a negative serum pregnancy test at study entry - Patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) are allowed on study if they have an undetectable viral load, cluster of differentiation (CD)4 > 300 and are on a stable highly active antiretroviral therapy (HAART) regimen for 1 month prior to study enrollment - Patients are required to have HER2+ breast cancer defined as a fluorescent in situ hybridization (FISH)- ratio of >= 2.0 or immunohistochemistry (IHC) 3+ - Patients for the triplet regimen (ganetespib, paclitaxel, trastuzumab): - Any number of prior chemotherapies or biological therapies are allowed, patients are required to have prior treatment with pertuzumab and ado-trastuzumab emtansine with the exceptions listed below: - Metastatic patients who have not received prior pertuzumab are eligible if: heavily pretreated prior to Food and Drug Administration (FDA) approval of pertuzumab (08-Jun-2012) for first line treatment of HER2+ MBC - Metastatic patients who have not received ado-trastuzumab emtansine are eligible if: heavily pretreated prior to FDA approval of ado-trastuzumab emtansine (22-Feb-2013) for the treatment of patients with HER2+ MBC who previously received trastuzumab and a taxane, separately or in combination - Patients for the triplet regimen + pertuzumab: - Prior hormonal therapy for ER+ and/or PR+ HER2+ disease in the metastatic setting is allowed. - Prior T-DM1 in the metastatic setting is allowed if patients have progressed within 6 months after treatment for early-stage disease. - No prior history of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued Exclusion Criteria: - Fewer than 21 days since last anti-tumor therapy, including chemotherapy, biologic except trastuzumab, experimental, immune, radiotherapy for the treatment of breast cancer, with the following exceptions: - Hormone therapy - Palliative radiation therapy involving =< 25% of marrow-bearing bone is allowed if completed within >= 14 days prior to first study treatment - Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable/evaluable disease - Major surgery within 4 weeks prior to first dose of ganetespib - Poor venous access for study drug administration - Study drug administration via indwelling catheters is allowed only if the catheter is made of silicone material - No prior chemotherapy in the metastatic setting is allowed. - Prior pertuzumab is not allowed in the metastatic setting. Pertuzumab given in the neoadjuvant and/or adjuvant setting is allowed. - History of intolerance or hypersensitivity to trastuzumab and/or pertuzumab - Adverse events related to trastuzumab, murine proteins, or any of the excipients that resulted in trastuzumab being permanently discontinued - History of severe (grade 3 or 4) allergic or hypersensitivity reactions to excipients (e.g., polyethylene glycol [PEG] 300 and polysorbate 80) - History of intolerance or hypersensitivity to paclitaxel and/or adverse events related to paclitaxel that resulted in paclitaxel being permanently discontinued - Peripheral neuropathy of grade >= 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, at the time of or within 3 weeks prior to the first study therapy - Baseline QTc > 470 msec (average of triplicate ECG recordings); a consistent method of QTc calculation must be used for each patient's QTc measurements. QTcF (Fridericia's formula) is preferred - Use of medications that have been linked to the occurrence of torsades de pointes - Patients will be eligible for the study if they discontinue any of the listed medications two weeks prior to registration and study enrollment - Stable regimen of antidepressants of the SSRI class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline and fluoxetine) - Left ventricular ejection fraction (EF) < 50% at baseline - Serum potassium, magnesium, and calcium levels (corrected for albumin) outside the laboratory's reference range despite correction - Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation) - Women who are pregnant or lactating - Current known active infection with HIV, hepatitis B or C viruses - Uncontrolled systemic disease (e.g., clinically significant cardiac, pulmonary or metabolic disease) - Other medications, or severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results in the judgment of the investigator - History of clinically significant cardiac dysfunction, including: - Unstable angina - Unstable atrial fibrillation - Symptomatic bradycardia - Indwelling temporary pacemaker - History of MI within 6 months prior to first study treatment - History of symptomatic CHF (grade > 3 by NCI CTCAE or Class > II by New York Heart Association (NYHA) criteria - Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class 1a antiarrhythmic drug (eg quinidine, procainamide, disopyramide) or Class III antiarrhythmic drug (eg sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted - Second or third degree atrioventricular (AV) block unless treated with a permanent pacemaker - Complete left bundle branch block (LBBB) - History of long QT syndrome or a family member with this condition - Brain metastases that are: - Progressive or - Have required any type of therapy (including radiation, surgery or steroids) to control symptoms from brain metastases within 60 days prior to the first study treatment - History of an invasive second primary malignancy diagnosed within the previous 3 years, except for appropriately treated stage I endometrial or cervical carcinoma or prostate carcinoma treated surgically, and non-melanoma skin cancer | |
| 59 | NCT02061449 | terminated | low accrual | 0.6773437261581421 | phase 1 | ['cutaneous t-cell lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['romidepsin', 'poly iclc'] | ['C\\C=C1/NC(=O)[C@H]2CSSCC\\C=C\\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C'] | Inclusion Criteria: - Must have prior biopsy at any time point diagnostic for confirmed MF stage IIA-IVA, and must have failed at least one standard therapy (topical or systemic). - Must have a skin lesion of at minimum 2 cm, in a location amenable to radiation and a minimum of 2 additional measurable skin lesions distant from the radiation site. - Must be either initiating therapy with romidepsin (Arm A) or currently receiving romidepsin with documented stable disease (SD) or partial response (PR) (Arm B). - Patient may have had any prior topical or systemic therapy except for total electron beam irradiation. Patients must be a minimum of 2 weeks from topical therapy and 4 weeks from systemic therapies, phototherapy, or local radiation therapy before enrollment except for HDACI if they are in Arm B. Patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month. - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >70%) - Life expectancy of greater than 6 months - Patients must have normal organ and marrow function as defined below: - leukocytes >=2,500/mcL - absolute neutrophil count >=1,000/mcL - platelets >=50,000/mcL - total bilirubin: within normal institutional limits - AST(SGOT, aspartate aminotransferase)/ALT(SGPT, alanine aminotransferase) =<2.5 X institutional upper limit of normal - creatinine: within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal. - Age >=18 years - The effects of focal radiation and HDACI on the developing human fetus are unknown. For this reason and because agents as well as other therapeutic agents used in this trial are known to be tetragenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. - Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: - Patients who have had chemotherapy or radiotherapy within 4 weeks, or topical therapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. Patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month. - Patients who are receiving any other investigational agents. - Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to HDACI, TLR-agonist, or patients with known history of pre-existing auto-immune disease. - Concurrent therapy with systemic corticosteroids or other immunosuppressive medications. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant women are excluded from this study HDACI is a class agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with HDACI, breastfeeding should be discontinued if the mother is treated with HDACI and radiation. Woman of childbearing age and men sexually active with woman of childbearing age must agree to an acceptable method of birth control (double barrier) while on study. - Patients with known HIV infection are ineligible because this immunomodulatory therapy requires a normal and functional T cell repertoire. If this study is found to be safe, effective, and immunogenic, HIV positive patients may be included in future studies. |
| 60 | NCT02064608 | completed | 0.4705679714679718 | phase 1 | ['prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['azd2014'] | ['[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC'] | Inclusion Criteria: - Men aged 18 years old or older - ECOG performance status of 0 or 1 - Clinical diagnosis of Intermediate (one or more of stage T2, or PSA >10ng/mL, or Gleason score of at least 7) or High Risk Prostate Cancer (one or more of stage T2c, or PSA >20ng/mL, or Gleason score of at least 8) - Patient suitable for radical prostatectomy, following discussion at specialist MDT and subsequent review by surgical team - Willing to use barrier contraceptive method, e.g. condom & spermicide - Adequate bone marrow reserve or organ function (as specified in the study protocol) - Normal chest radiograph and oxygen saturations, OR normal CT thorax Exclusion Criteria: - Contraindication to AZD2014 (as specified in the study protocol) - Patients who have experienced any of the following procedures in the past 12 months: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; congestive heart failure (New York Heart Association grade of 2 or above); ventricular arrhythmias requiring continuous therapy; supraventricular arrhythmias including atrial fibrillation, which are uncontrolled; haemorrhagic or thrombotic stroke including transient ischaemic attacks or any other CNS bleeding. - Previous chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents and/or investigational agents within 28 days of starting study treatment. - Major surgery within 4 weeks prior to study entry (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study - Potent or moderate inhibitors and inducers of CYP2C8 if taken within the stated wash-out period: Gemfibrozil, trimethoprim, glitazones, montelukast, deferasirox and quercetin (1-week minimum wash out period) - Any haematopoietic growth factors, e.g. G-CSF, GM-CSF, within 4 weeks prior to receiving study drug - As judged by the Investigator, any evidence of severe or uncontrolled systemic disease (as specified in the study protocol) - Abnormal ECHO or MUGA at baseline - Mean resting QTc of 470msec or above (as per local reading) - Concomitant medications known to prolong QT interval, or with factors that increase the risk of QTc prolongation, or risk of arrythmic events (examples specified in study protocol). History of Torsades de Pointes. - Patients with Diabetes Type I or uncontrolled Type II as judged by the investigator - Judgement by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements. - Unable to provide informed consent | |
| 61 | NCT02065466 | withdrawn | lack of accrual | 0.4806535542011261 | phase 1/phase 2 | ['metastatic melanoma', 'brain metastases'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['nab-paclitaxel', 'temozolomide', 'bevacizumab'] | ['[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C', 'CSCC[C@H](N)C(O)=O', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Histologically or cytologically confirmed malignant melanoma and clinical evidence of metastatic disease to the brain. Mucosal and ocular melanomas are included. - Newly developed inoperable brain metastases without associated hemorrhage or midline shift. - Inoperable or metastatic extra cranial stage III or IV disease. - Diagnostic quality MRI of the brain or if contraindicated then contrast CT scan of the head performed within 28 days prior to registration. - Measurable metastases to the brain, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm in the brain MRI/CT scan. - CT scan chest, abdomen and pelvis or PET CT scan performed within 28 days of study registration. For disease outside the brain, tumors must be > 10 mm by CT scan. - Prior therapy allowed but no prior therapy with nab-paclitaxel, paclitaxel, temozolomide, DTIC or bevacizumab. - Bevacizumab may not be initiated until 4 weeks after surgical resection or radiation therapy completion. - Age 18 or older. - Pre-existing peripheral neuropathy must have < Grade 2 (per CTCAE 4.0) at the time of registration. - Negative serum or urine β-hCG pregnancy test at screening for patients of childbearing potential. - Women of childbearing potential and sexually active males must use an effective contraception method during treatment and for three months after completing treatment. - ECOG Performance status 0-1. - Estimated life expectancy of greater than 2 months. - Patients must have adequate organ function as defined below (these must be evaluated within 14 days prior to registration): - leukocytes >3,000/mcL - absolute neutrophil count >1,500/mcL - platelets >100,000/mcL - Hemoglobin >9.0 g/dL - AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit - Alkaline phosphatase <2.5 X institutional upper limit - Total bilirubin <1.5 X institutional upper limit of normal (unless associated with Gilbert's syndrome) - serum creatinine < 1.5 mg/dL OR 1.5 x institutional normal - LDH there is no restriction - INR <1.5 PTT WNL - Urine protein (UPC) ratio 1.0 OR - Urine dipstick for proteinuria. Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible). - Able to render informed consent. Exclusion Criteria: - Prior surgical resection for brain metastases. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, nab-paclitaxel or temozolomide. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics, symptomatic congestive heart failure, unstable angina pectoris, untreated cardiac arrhythmia and peripheral vascular disease. - History of myocardial infarction or unstable angina within 6 months prior to Day 1. - History of stroke or transient ischemic attack within 6 months prior to Day 1. - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study screening. - Serious, non-healed wound, ulcer, or bone fracture. - History of hepatitis B, C or HIV. - Uncontrolled hypertension or chronic renal disease. No known bleeding diathesis. - Known hypersensitivity to human albumin. - Surgery within 4 weeks of study registration. Must be fully recovered and fully healed from any prior surgery. - Patients having chemotherapy or extra cranial radiotherapy within 4 weeks prior to study screening or those who have not recovered from adverse events due to agents administered more than 4 weeks prior to the completion of study screening. - Evidence of other concurrent active malignancy. - Pregnant or nursing. - Not be receiving any other investigational agent. |
| 62 | NCT02069119 | completed | 0.5825721025466919 | phase 1 | ['atrial fibrillation'] | ["['I48.0', 'I48.21', 'I48.91', 'I48.11', 'I48.19', 'I48.20']"] | ['opc-108459', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Japanese - Male or female age 20 to 85 years, inclusive (at the time of informed consent) - Patients diagnosed with recent or new onset of paroxysmal AF (3 hours to 7 days since the onset) or persistent AF (8 to 30 days since the onset) at time of randomization (prior to Investigational Medicinal Product [IMP] administration). Review of the patient's medical records and the judgment of the investigator or sub-investigator must be documented in the source documents to establish the date and duration of the most recent onset of AF. - Patients who are receiving treatment according to the "Guidelines for Pharmacotherapy of Atrial Fibrillation (JCS 2008)" at time of screening and predosing examinations or who have a low risk of thromboembolic potential specified as follows: - AF lasting less than 48 hours, OR - For AF lasting for 48 hours or longer: - Patients receiving warfarin therapy for whom at least 3 weeks have elapsed since achieving an international normalized ratio (INR) of 2.0 to 3.0 (1.6 to 2.6 for patients age 70 years or older) or in whom no thrombus in the atrial main body or appendage is observed by transesophageal echocardiography (TEE) within 24 hours before IMP administration - Patients in whom no thrombus in the atrial main body or appendage is observed by TEE within 24 hours before IMP administration if they have not undergone antithrombotic therapy or if they have undergone antithrombotic therapy (including a new oral antithrombotic drug) which does not meet the above criterion - Patients with systolic blood pressure (sBP) of 90 mmHg or higher and lower than 160 mmHg and diastolic blood pressure (dBP) of lower than 100 mmHg at screening examinations - Female patients who have been postmenopausal for at least 12 consecutive months, or male and female patients who agree, together with their partners, to practice birth control as specified until 3 months after the start of IMP administration or who are surgically sterile (ie, have undergone orchiectomy or hysterectomy, respectively) Exclusion Criteria: - QRS interval of > 120 msec - Patients with heart failure of New York Heart Association (NYHA) Class II to IV or with left ventricular ejection fraction (LVEF) of < 40% - Patients who currently have or have a history of a long QT syndrome, torsade de pointes, or an uncorrected QT interval of > 450 msec - History of ventricular tachycardia, ventricular fibrillation, or resuscitated cardiac arrest - History of AF and failed electrical or pharmacological cardioversion - Current diagnosis of atrial flutter - Patients with bradycardia (< 50 beats per minute [bpm]) or sick sinus syndrome, unless controlled by a pacemaker, except for physiologically transient sinus bradycardia observed at rest or during sleep - Patients with Wolff-Parkinson-White syndrome - Patients with any congenital severe heart disease - Patients with severe aortic or mitral stenosis (aortic-valve area, < 1 cm2), severe mitral regurgitation, aortic regurgitation, congenital atrial septal defect, moderate or severe pulmonary hypertension, or any other disease leading to AF confirmed by echocardiography within one year prior to screening examinations - Patients diagnosed with congenital valvular anomaly or severe valve disease (eg, aortic or mitral stenosis, severe right or left ventricular systolic dysfunction, or severe pulmonary hypertension) and confirmed current presence of the condition by TEE at screening examinations - Patients diagnosed with stroke or transient ischemic attack within one year prior to screening examinations or with carotid artery stenosis of 50% - History of myocardial infarction within 6 months prior to screening examinations - Findings of acute coronary syndrome, angina, or myocardial ischemia diagnosed by ECG or drug-induced or exercise stress testing within 6 months prior to screening examinations | |
| 63 | NCT02070406 | terminated | low accrual | 0.5357454419136047 | phase 1 | ['unspecified adult solid tumor, protocol specific'] | ["['H01.009', 'H02.209', 'H02.009', 'H02.109', 'H04.209', 'H05.409', 'H10.509']"] | ['cyclophosphamide', 'fludarabine phosphate'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O'] | Inclusion Criteria: - Stage IV or locally advanced cancers for which no alternative therapies with proven survival advantage are available - At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists; patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion - NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly available NY-ESO-1 antibodies - Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping - Life expectancy greater than 3 months assessed by a study physician - A minimum of one measurable lesion defined as: - Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) - Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s) - No restriction based on prior treatments - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 - Absolute neutrophil count >= 1.5 x 10^9 cells/L - Platelets >= 100 x 10^9/L - Hemoglobin >= 10 g/dL - Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (=< 5 x ULN, if documented liver metastases are present) - Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) - Creatinine < 2 mg/dl (or a glomerular filtration rate > 60) - Must be willing and able to accept two leukapheresis procedures - Must be willing and able to provide written informed consent Exclusion Criteria: - Previously known hypersensitivity to any of the agents used in this study - Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol - History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves' disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.); patients will be eligible if prior autoimmune disease is not deemed to be active (e.x. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy); vitiligo will not be a basis for exclusion - History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin - Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed) - Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist - Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist - Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol - Clinically active brain metastases; radiological documentation of absence of active brain metastases at screening is required for all patients; prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment - Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators - Since IL-2 is administered following cell infusion: - Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multi gated acquisition (MUGA) scan, dobutamine echocardiogram, or other stress test) - Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded - Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 PVCs per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist - Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume of the lung in 1 second (FEV1)/forced vital capacity (FVC) < 70% of predicted for normality will be excluded - Evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only |
| 64 | NCT02071537 | completed | 0.5980634689331055 | phase 1 | ['malignant neoplasm', 'solid tumors'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['chloroquine', 'carboplatin', 'gemcitabine'] | ['CCN(CC)CCCC(C)NC1=C2C=CC(Cl)=CC2=NC=C1', 'N[C@@H](CCCNC(N)=N)C(O)=O', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Histologically confirmed diagnosis of a malignancy that is metastatic or unresectable and for which either standard curative measures do not exist or are no longer effective and carboplatin/gemcitabine is considered a reasonable treatment option whether first line or acceptable and approved combination therapy. - Age >18 years of age. - Performance status less than or equal 2 (Karnofsky >60%) - Life expectancy of greater than 3 months. - Adequate labs - Measurable disease Exclusion Criteria: - Current treatment with any other investigational agents. - Patients with untreated brain metastases - History of allergic reaction attributed to compounds of similar chemical or biologic composition to chloroquine or other agents used in study. | |
| 65 | NCT02073123 | completed | 0.4853751063346863 | phase 1/phase 2 | ['metastatic melanoma', 'stage iii melanoma', 'stage iv melanoma'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']", "['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']", "['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['indoximod', 'ipilimumab', 'nivolumab', 'pembrolizumab'] | ['CN1C=C(C[C@@H](N)C(O)=O)C2=CC=CC=C12', 'COC1=CC=CC=C1OCC(O)CO', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Unresectable Stage III or Stage IV melanoma. - Patients must have measurable disease, defined as lesions that can be accurately measure in in 2 perpendicular diameters with at least one diameter > 20mm and the other >10mm on conventional CT or MRI or 10mm x 10 mm by spiral CT. - No systemic treatment in the previous 28 days. - Age ≥18 years. Because no dosing or adverse event data are currently available on the use of ipilimumab or indoximod in patients <18 years of age, children are excluded from this study. - ECOG performance status ≤2 (Karnofsky ≥60% ) - Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids. Exclusion Criteria: - Patients who have had molecular targeted therapy (including vemurafenib) or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. - Patients who have had prior therapy with immune checkpoint inhibition or or indoximod are excluded from the trial. - Any other cancer, unless the patient has been disease-free for ≥5 years - Patients with laboratory evidence of pancreatitis are excluded. - Patients with autoimmune disease - Chronic use of immune-suppressive drugs (ie, systemic corticosteroids used in the management of cancer or non-cancer related illnesses, eg, COPD). | |
| 66 | NCT02074839 | recruiting | 0.6218962669372559 | phase 1 | ['relapsed or refractory acute myeloid leukemia (aml)', 'untreated aml', 'other idh1-mutated positive hematologic malignancies', 'myelodysplastic syndromes'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['ag-120'] | ['[H][C@@](N(C(=O)[C@]1([H])CCC(=O)N1C1=NC=CC(=C1)C#N)C1=CC(F)=CN=C1)(C(=O)NC1CC(F)(F)C1)C1=C(Cl)C=CC=C1'] | Key Inclusion Criteria: - Subject must be ≥18 years of age. - Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based on local or central evaluation. - Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling, and urine sampling during the study. - Subjects must have ECOG PS of 0 to 2. - Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed). - Subjects must have adequate hepatic function as evidenced by: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or leukemic disease - Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 × ULN or creatinine clearance >40mL/min based on Cockroft-Gault glomerular filtration rate (GFR) - Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer. - Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration. Key Exclusion Criteria: - Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical for ongoing skin GVHD is permitted.) - Subjects who received systemic anticancer therapy or radiotherapy <14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120). - Subjects who received an investigational agent <14 days prior to their first day of study drug administration. - Subjects who are pregnant or breastfeeding. - Subjects with an active severe infection or with an unexplained fever >38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled). - Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1. - Subjects with a history of myocardial infarction within the last 6 months of screening. - Subjects with a known unstable or uncontrolled angina pectoris. - Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias. - Subjects with known unstable or uncontrolled angina pectoris. - Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events. - Patients taking medications that are known to prolong the QT interval - Subjects with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C. - Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening. - Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation. | |
| 67 | NCT02074878 | terminated | poor accrual so the study was halted on may 16, 2017. | 0.5532837510108948 | phase 1 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['crixotinib 200 mg and sunitinib cohort 1', 'crixotinib 250 mg and sunitinib cohort 2', 'crizotinib & sunitinib 37.5 mg cohort 3'] | ['CNC(=O)C1=C(SC2=CC=C3C(NN=C3\\C=C\\C3=CC=CC=N3)=C2)C=CC=C1', 'CNC(=O)C1=C(SC2=CC=C3C(NN=C3\\C=C\\C3=CC=CC=N3)=C2)C=CC=C1', 'C[C@@H](OC1=CC(=CN=C1N)C1=CN(N=C1)C1CCNCC1)C1=C(Cl)C=CC(F)=C1Cl'] | Inclusion Criteria: 1. Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up. 2. Age of at least 18 years 3. Histologically confirmed diagnosis of stage IV, HER2 negative breast cancer. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 5. Patients must have failed two lines of systemic therapy for breast cancer. Patients who are hormone receptor positive must have failed at least one line of hormonal therapy AND one line of chemotherapy in the metastatic setting. 6. Life expectancy of 6 months or more. 7. Liver function (ALT, AST, alkaline phosphatase, total bilirubin) and kidney function tests (BUN, creatinine) less than 2.5 times the upper limit of normal. In patients with liver metastasis, liver function tests should be less than 5 times the upper limit of normal. 8. Adequate blood counts (Hemoglobin greater than/equal to 10, WBC greater than/equal to 3.0, platelets greater than/equal to 100). 9. The patient has normal thyroid function tests (TSH, free T4) as defined by the testing laboratory, a test abnormality that is asymptomatic and does not warrant medical intervention, or a pre-existing thyroid disorder that is controlled on medical treatment. 10. Negative pregnancy test (BHCG) within 14 days of study drug initiation for pre- or perimenopausal subjects with an intact uterus. Exclusion Criteria: 1. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding. 2. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational products. 3. Presence of uncontrolled infection. 4. Corrected QT interval (QTc) > 480 msecs using Bazett's formula 5. History of any one or more of the following cardiovascular conditions within the past 6 months: - Cardiac angioplasty or stenting - Myocardial infarction - Unstable angina - Coronary artery bypass graft surgery - Symptomatic peripheral vascular disease - Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) 6. Poorly controlled hypertension (defined as systolic blood pressure [SBP] of > 150 mmHg or diastolic blood pressure [DBP] of > 90 mmHg). 7. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months. Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible. 8. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major). 9. Evidence of active bleeding or bleeding diathesis. 10. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels 11. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks prior to first dose of study drug. 12. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. 13. Patients previously treated with sunitinib or crizotinib. 14. History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma of the skin. 15. Concurrent use of: - Potent CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, amprenavir, indinavir, nelfinavir, delavirdine and voriconazole. - CYP3A4 inducers: rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John's Wort, and dexamethasone. Use of dexamethasone for study premedication is allowed. - Grapefruit and grapefruit juice. (Note: Alternative therapies should be used when available. If use of a potent CYP3A4 inhibitor or inducer is necessary, this must be approved by the principal investigator and documented in source documents). 16. History of receiving any investigational treatment within 28 days of study medication initiation. 17. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, thyroid, or metabolic disease; wound healing disorders; ulcers; or bone fractures). 18. Patients who are pregnant or lactating. |
| 68 | NCT02077881 | completed | 0.4331299066543579 | phase 1/phase 2 | ['metastatic pancreatic adenocarcinoma', 'metastatic pancreatic cancer'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C25.3']"] | ['nab-paclitaxel', 'gemcitabine', 'indoximod'] | ['[H][C@]12[C@H](OC(=O)C3=CC=CC=C3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)C4=CC=CC=C4)C4=CC=CC=C4)C(C)=C([C@@H](OC(C)=O)C(=O)[C@]1(C)[C@@H](O)C[C@H]1OC[C@@]21OC(C)=O)C3(C)C', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CN1C=C(C[C@@H](N)C(O)=O)C2=CC=CC=C12'] | Inclusion Criteria: - Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. Patients with islet cell or neuroendocrine neoplasms are excluded. - Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in the study. - Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4 weeks prior to entry into the study - Male or non-pregnant and non-lactating female, and ≥18 years of age. - Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease. - Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. - Patients cannot have received any other immunomodulatory therapies (including vaccines) as treatment for this or any other cancer. - Patient has a Karnofsky performance status (KPS) ≥ 70. - Patients should be asymptomatic for jaundice prior to Day 1. Exclusion Criteria: - Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease. - Patient has known brain metastases, - Patient has only locally advanced disease. - Lymph node only metastases even if considered M1 disease by official staging criteria. - History of malignancy in the last 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years. - Patients with any active autoimmune disease - Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study. | |
| 69 | NCT02078089 | terminated | poor accrual | 0.584610641002655 | phase 1 | ['cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['morphine', 'oxcarbazepine'] | ['CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O', 'NC(=O)N1C2=CC=CC=C2CC(=O)C2=C1C=CC=C2'] | Inclusion Criteria: - Written informed consent and HIPAA authorization for release of personal health information. •≥ 18 years old at the time of informed consent - Patients with histologically confirmed diagnosis of cancer NOTE: Patients with active cancer or post treatment are allowed on the study. - Patients must be receiving stable or increasing doses of morphine for 1-2 weeks prior to registration for protocol therapy. NOTE: Switching patient from current pain regimen to morphine equivalent for at least 1-2 weeks prior to registration for protocol therapy is required. - Requiring greater than or equal to 180 mg of morphine per day. See Appendix 1 for Morphine Conversion Calculator. - Inadequately controlled pain even with the use of morphine (VAS score >5) See Appendix 8 - Rescue pain medications are allowed this may include the use of NSAIDS or Tylenol as well as morphine IR. - ECOG Performance Status of 0-2 - Ability to swallow and tolerate oral tablets. - Patients getting radiation therapy are allowed at the discretion of the treating physician. - Females of childbearing potential must have a negative pregnancy test NOTE: Females are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (> 12 months since last menses). NOTE: Females using hormonal contraceptives should be switched to non-hormonal forms of contraception. The following laboratory values must be obtained. Patient with aplastic anemia will be excluded. - White blood cell count (WBC) ≥ 3.0 K/mm3 - Absolute neutrophil count ≥ 1.5 K/mm3 - Hemoglobin (Hgb) ≥ 9 g/dL - Platelets ≥ 75 K/mm3 - Creatinine ≤ 1.5 mg/dl - Bilirubin ≤ 1.5 x ULN - Aspartate aminotransferase (AST, SGOT) ≤ 3 x ULN - Alanine aminotransferase (ALT, SGPT) ≤ 3 x ULN Exclusion Criteria: • Active central nervous system (CNS) metastases. Patients with neurological symptoms should undergo a head CT scan or brain MRI to exclude brain metastasis, at the discretion of the treating physician. NOTE: Patients with prior brain metastasis may be considered if they have completed their treatment for brain metastasis, no longer require corticosteroids, and are asymptomatic. • Concurrent use of adjuvant medication such as but not limited to: gabapentin, pregabalin or duloxetine etc. NOTE: Patients on gabapentin or pregabalin can be considered if they can be tapered off before enrolling on the study. - Treatment with any investigational agent within 30 days prior to registration for protocol therapy. - Patient with rapidly escalating pain that require hospitalization or an intravenous opioid therapy - Concurrent participation in a clinical trial which involves another investigational agent. - Concurrent use of medications that are strong CYP3A4 inhibitors within 14 days prior to registration for protocol therapy as Oxcarbazepine is strong CYP3A4 inducer. See Appendix 7. NOTE: Concurrent use of other CYP3A4 inhibitors may be allowed at the discretion of the treating physician or principal investigator. - Allergic reaction to carbamazepine or oxcarbazepine (HLA-B1502) - Allergy or other contraindication to morphine sulphate - Opiate-induced uncontrolled constipation or bowel obstruction - Patient who lives alone. - Female who is pregnant or breastfeeding - Patient who has a diagnosis of epilepsy and/or is currently taking anti-epileptic drugs |
| 70 | NCT02078310 | completed | 0.5072385668754578 | phase 1/phase 2 | ["alzheimer's disease"] | ["['G30.8', 'G30.9', 'G30.0', 'G30.1']"] | ['iti-007', 'placebo', 'iti-007', 'placebo'] | ['[H][C@]12CCN(CCCC(=O)C3=CC=C(F)C=C3)C[C@@]1([H])C1=CC=CC3=C1N2CCN3C', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@]12CCN(CCCC(=O)C3=CC=C(F)C=C3)C[C@@]1([H])C1=CC=CC3=C1N2CCN3C', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: Part 1 - Healthy geriatric volunteers - MMSE score of >= 26 at screening - BMI between 19.0 and 40.0 kg/m2 and a minimum body weight of 50 kg at screening Part 2 - Geriatric patients with a clinical diagnosis of dementia - MMSE score of < 26 at screening - BMI between 19.0 and 40.0 kg/m2 and a minimum body weight of 50 kg at screening Exclusion Criteria: - Any clinically significant illness within 6 months before screening - Any history of cancer within last 5 years - History of Hepatitis B or C infection and elevated ALT, AST or bilirubin above the upper limit of normal level - Any subject considered to be an imminent danger to themselves or others | |
| 71 | NCT02078648 | completed | 0.4502435028553009 | phase 1/phase 2 | ['adult brain glioblastoma', 'glioblastoma multiforme'] | ["['L51.0', 'L51.8', 'L51.9']"] | ['bevacizumab'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - 18 years of age or older. - Histologically confirmed GBM or World Health Organization (WHO) Grade IV variants (gliosarcoma, glioblastoma with oligodendroglial features, or giant cell glioblastoma). - Uneqivocal evidence of a first tumor recurrence or progression on the initial treatment regimen (prior to enrollment on this study), consisting of surgical intervention (biopsy and/or resection), radiation, and temozolomide chemotherapy, as assessed by MRI or CT scan of the brain with or without contrast within 14 days prior to the start of SL-701. If receiving corticosteroids, the dose must be stable or decreasing for at least 5 days prior to the scan. Patients unable to undergo MRI because of non-compatible devices can be enrolled, provided CT scans are obtained and are of sufficient quality. For each patient, the same imaging technique should be performed throughout the study, for purposes of assessing tumor response or PD. - For patients who have undergone resection of recurrent or progressive tumor prior to study enrollment, the following conditions must apply: - Recovery from the effects of surgery. - Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease post-operatively, an MRI should be performed: - No later than 96 hours (h) in the immediate post-operative period; or - At least 4 weeks post-craniotomy (7 days for stereotactic biopsy), within 14 days prior to the start of SL-701, and on a corticosteroid dosage that has been stable or decreasing for at least 5 days. - Patients who have not had resection of recurrent or progressive disease must have measurable disease. - At least 56 of the approximately 76 patients treated must have measurable disease, defined as at least one, contrast-enhancing lesion measuring at least 1 cm in 2 planes (axial, coronal, or sagittal). - No evidence of hemorrhage on the baseline MRI or CT scan other than those that are Grade ≤ 1 and either post-operative or stable on at least two consecutive scans. - Recovery from prior therapy toxicity, defined as resolution of all treatment-related adverse events (AEs) to Grade ≤ 1 or pre-treatment baseline (except alopecia and lymphopenia). - At least 12 weeks from prior radiotherapy to the start of SL-701 unless there is new enhancement outside of the radiation field or unequivocal histopathologic evidence of recurrent tumor. - No chemotherapy or investigational agent for at least 3 weeks prior to the start of SL-701, with at least 6 weeks of elapsed time from last dose of nitrosoureas. - Human leukocyte antigen (HLA)-A2 positive. - A tumor tissue sample is provided for immunohistochemical analysis of relevant antigens, immune markers and potential prognostic factors. Preferably a paraffin block or 10-12 unstained slides will be submitted prior to study entry. Patients for whom tumor samples are unavailable or inadequate are permitted to participate in the study; however, the absence of available/adequate tumor specimen must be documented. - Karnofsky performance status (KPS) score ≥ 70%. - Adequate organ function, including the following: - Absolute neutrophil count (ANC) ≥ 1,000/μL, platelets ≥ 100,000/μL. - Serum creatinine < 1.5 × the upper limit of normal (ULN). - Bilirubin < 1.5 × ULN. - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN. - Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the start of SL-701 treatment. - Female patients of childbearing potential and sexually active male patients must agree to use an acceptable form of contraception for heterosexual activity (ie, oral contraceptives, double barrier methods, hormonal injectable, transdermal, or implanted contraceptives, tubal ligation, or vasectomy of their sexual partner(s) for > 40 days before Screening, during the study, and for 60 days after the last dose of study drug. Men should not donate semen during the study and for 60 days after the last dose of study drug. - Female patients without childbearing potential (spontaneous amenorrhea for > 12 months or surgically sterilized by tubal ligation, hysterectomy, or bilateral oophorectomy > 6 months before Screening) are eligible for inclusion without contraceptive use restriction. - Able and willing to comply with protocol requirements, in the opinion of the investigator. - A written and voluntarily signed informed consent must be obtained from the patient or legally authorized representative, in accordance with local regulations, before the initiation of any study related procedures. The patient or legally authorized representative must be able to read and understand the informed consent form (ICF). Exclusion Criteria: - Prior cancer chemotherapy, bevacizumab (or other vascular endothelial growth factor [VEGF]/VEGF receptor [VEGFR]-directed agent), or an investigational agent for recurrent/progressive GBM or prior bevacizumab as part of initial therapy (prior chemotherapy or investigational agents are permitted as part of initial therapy; VEGF/VEGFR-directed agents are not permitted). - Contrast-enhancing tumor that is any of the following: - Multi-focal (defined as two separate areas of contrast enhancement measuring at least 1 cm in 2 planes that are not contiguous on either fluid-attenuated inversion recovery (FLAIR) or T2 sequences); - Associated with either diffuse subependymal or leptomeningeal dissemination; or - ≥ 4 cm in any dimension. - Requirement of systemic corticosteroid therapy > 4 mg/day of dexamethasone or equivalent or requirement of increasing dose of systemic corticosteroids during the 7 days prior to the start of SL-701 treatment. - Surgical resection or major surgical procedure within 4 weeks prior to the start of SL-701, or stereotactic biopsy within 7 days prior to the start of SL-701. - Radiation therapy, local therapy (except for surgical re-resection), or systemic therapy following first recurrence/progressive disease. Excluded local therapies include stereotactic radiation boost, implantation of carmustine biodegradable wafers (Gliadel), intratumoral or convection-enhanced delivery administered agents, etc. - Active infection requiring intravenous antibiotics. - History of cancer (other than GBM) within the past 2 years that has metastatic or local recurrence potential and could negatively impact survival and/or potentially confound tumor response assessments within this study. - Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication). - Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus infection, Hepatitis B, or Hepatitis C, or has taken an immunosuppressive agent within 4 weeks prior to the start of SL-701 treatment. Patients with vitiligo, type 1 diabetes mellitus, hypothyroidism due to autoimmune condition only requiring hormone replacement therapy, psoriasis not requiring systemic therapy, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. - Any condition which in the investigator's opinion makes the patient unsuitable for study participation. - Requires therapeutic anticoagulation with warfarin at baseline; patients must be off warfarin or warfarin-derivative anti-coagulants for at least 7 days prior to starting study drug; however, therapeutic or prophylactic therapy with low-molecular weight heparin is allowed. - Has history of known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhage within 12 months of start of study drug. - Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are ≤Grade 1 and either post-operative or stable on at least 2 consecutive MRI scans - Has gastrointestinal bleeding or any other hemorrhage/bleeding event National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) >Grade 3 within 6 months of start of study drug. | |
| 72 | NCT02078960 | terminated | inability to accrue additional sites and enroll an adequate number of subjects. | 0.5525831580162048 | phase 1/phase 2 | ['chronic myeloid leukemia'] | ["['C92.11', 'C92.12', 'C92.21', 'C92.22', 'C92.10', 'C92.20']"] | ['omacetaxine mepesuccinate'] | ['[H][C@@]1(OC(=O)[C@@](O)(CCCC(C)(C)O)CC(=O)OC)C(OC)=C[C@]23CCCN2CCC2=CC4=C(OCO4)C=C2[C@]13[H]'] | Inclusion Criteria: - The patient has a confirmed diagnosis of Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either CP or AP. Accelerated phase will be defined as disease having 1 of the following: ≥15% to <30% blasts in peripheral blood or bone marrow; ≥30% blasts + promyelocytes in peripheral blood or bone marrow; ≥20% basophils in peripheral blood or bone marrow; platelet count <100x109/L unrelated to therapy; or clonal evolution. - The patient has either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least 2 tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response). - TKI treatment failure will be defined as 1 of the following: - no CHR by 12 weeks (whether lost or never achieved) - no partial cytogenetic response by 24 weeks (ie, 1 to 35% Ph-positive) (whether lost or never achieved) no major cytogenetic response by 52 weeks (ie, ≤35% Ph-positive) (whether lost or never achieved) - progressive leukocytosis, defined as increasing white blood cell (WBC) count on at least 2 consecutive evaluations, at least 2 weeks apart and doubling from the nadir to ≥20000/μL or absolute increase in WBC by ≥50000/μL above the post-treatment nadir - Intolerance to TKI therapy will be defined as 1 of the following: - grade 3 to 4 nonhematologic toxicity that does not resolve with adequate intervention - grade 4 hematologic toxicity lasting more than 7 days, or a documented inability to sustain the TKI therapy because of recurrent grade 3 or 4 hematologic toxicity with re-initiation of the same therapy - any grade 2 or greater toxicity that is unacceptable to the patient - Patients must have completed all previous anticancer therapy for at least 2 weeks prior to the first planned dose of omacetaxine, except as noted below, and must have fully recovered from side effects of a previous therapy. - In patients with rapidly proliferating disease, hydroxyurea may be administered before study entry, if clinically indicated, to control disease. In such cases, complete hematologic response (CHR) must be sustained for at least 4 weeks for accelerated CML, and at least 8 weeks for chronic phase CML, following the discontinuation of hydroxyurea, to be considered as a CHR. - Patients may receive anagrelide for up to 28 days (in countries where the product is registered). Leukapheresis is allowed up to 24 hours prior to the first treatment cycle with omacetaxine. - Patients must have adequate hepatic and renal function as evidenced by bilirubin 2.0 times the upper limit of the normal range (ULN) or lower, alanine aminotransferase (ALT) and asparate aminotransferase (AST) 3 times the ULN or lower, serum creatinine 1.5 times the ULN or lower. Patients with nonclinically significant elevations of bilirubin up to 5.0 g/dL (85500 μmol/L) due to known or suspected Gilbert's disease are eligible; this must be documented on the medical history page of the case report form (CRF). - Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 - Patients are men or women at least 18 years of age. - Patients must be able and willing to provide written informed consent prior to any study related procedure. - The patient must take precautions to not become pregnant or produce offspring. Women must be of non-childbearing potential (surgically sterile or postmenopausal for at least 12 months, confirmed by follicle-stimulating hormone [FSH] >40 IU/L) or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Men must be surgically sterile or agree to use a medically accepted method of contraception for the duration of the study and 90 days after treatment. Acceptable methods of contraception include abstinence, barrier method with spermicide (excluding cervical cap and sponge), intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. - Other criteria may apply, please contact the investigator for additional information Exclusion Criteria: - The patient has New York Heart Association (NYHA) class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, or congestive heart failure. - The patient has had a myocardial infarction in the previous 12 weeks. (Prior to study entry, electrocardiogram [ECG] abnormalities at screening must be documented by the investigator as not medically relevant.) - The patient has received radiotherapy within 30 days prior to the start of study drug, or has not recovered from the acute toxicities associated with prior approved therapies including investigational drugs. - The patient has another concurrent illness that would preclude study conduct and assessment, including, but not limited to, another active malignancy (excluding squamous or basal cell skin cancer and in situ cervical cancer), uncontrolled medical conditions, uncontrolled and active infection (considered opportunistic, life threatening, or clinically significant), uncontrolled risk of bleeding, or uncontrolled diabetes mellitus. - The patient underwent autologous or allogeneic stem cell transplant within 60 days prior to receiving the first dose of omacetaxine and has any evidence of ongoing graft versus host disease (GVHD), or GVHD requiring immunosuppressive therapy. - The patient has a human leukocyte antigen (HLA)-matched donor and is eligible for allogeneic transplantation for CML treatment. - The patient has known positive human immunodeficiency virus (HIV) or known active human t-cell lymphotropic virus (HTLV) I/II disease, whether on treatment or not. - The patient has known active hepatitis B or C. The determination of active hepatitis B or C is left to the investigator. - The patient has lymphoid Ph+ blast crisis or blast phase CML. - The patient participated in another clinical investigation within 30 days of enrollment or is receiving another investigational agent. - The patient received omacetaxine or has a history of hypersensitivity. - Other criteria may apply, please contact the investigator for additional information |
| 73 | NCT02079844 | completed | 0.5446359515190125 | phase 1 | ['schizophrenia'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']"] | ['roflumilast', 'placebo', 'second generation antipsychotic'] | ['FC(F)OC1=C(OCC2CC2)C=C(C=C1)C(=O)NC1=C(Cl)C=NC=C1Cl', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl'] | Inclusion Criteria: 1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. 2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. Meets schizophrenia criteria as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) by the Mini International Neuropsychiatric Interview (MINI). 4. On a stable dose of second generation antipsychotics (SGA) for at least 2 months as documented by medical history and assessed by site staff. 5. Meets the following symptom criteria: (a) Positive and Negative Syndrome Scale (PANSS) Conceptual Disorganization item score ≤4 (b) PANSS Hallucinatory Behavior or Unusual Thought Content item scores ≤4 (c) PANSS Negative Subscale scores on all items ≤4. 6. Has cognitive impairment as per investigator judgment. 7. Is aged 18 to 55 years, inclusive, at the time of informed consent. 8. Weighs at least 60 kg and has a body mass index (BMI) between 18 and 32 kg/m^2 inclusive at Screening. 9. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 10. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use acceptable methods of contraception from signing of informed consent throughout the duration of the study and for 12 weeks after last dose. 11. Has clinical laboratory evaluations (including clinical chemistry, hematology and complete urinalysis) within the reference range for the testing laboratory, unless the results are deemed not to be clinically significant (NCS) by the investigator at screening and Day 1 of Period 1. Exclusion Criteria: 1. Has received any investigational compound within 30 days prior to the first dose of study medication. 2. Has received roflumilast in a previous clinical study or as a therapeutic agent. 3. Is an immediate family member, study site employee, or in a dependant relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress. 4. Has uncontrolled, clinically significant neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results. 5. History of claustrophobia or inability to tolerate mock scanner environment during habituation/screening session. 6. Fulfillment of any of the magnetic resonance imaging (MRI) contraindications on the standard radiography screening questionnaire at the Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London (ie, history of surgery involving metal implants, metal body piercing, dentures, dental plates or bridges, any implanted device that is electrically, magnetically, and mechanically activated). 7. Has a known hypersensitivity to any component of the formulation of roflumilast. 8. Has a positive urine drug result for drugs of abuse at Screening or Day 1 for each treatment period. 9. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 6 months prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study. 10. The participant with a history in the last year or currently receiving treatment with clozapine. 11. Has taken any excluded medication, supplements, or food products. 12. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. 13. Has evidence of current cardiovascular, hepatic, hematopoietic disease, renal dysfunction, metabolic or endocrine dysfunction, serious allergy, asthma hypoxemia, hypertension, seizures, or allergic skin rash. There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking roflumilast or a similar drug in the same class, or that might interfere with the conduct of the study. This includes, but is not limited to, peptic ulcer disease, seizure disorders, and cardiac arrhythmias. 14. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (ie, a history of malabsorption, esophageal reflux, peptic ulcer disease, or erosive esophagitis frequent occurrence [more than once per week] of heartburn). 15. History of any surgical intervention known to impact absorption (eg, bariatric surgery or bowel resection). 16. Has a history of cancer within the past 5 years prior to the first dose of study medication. This criterion does not include those participants with basal cell or stage I squamous cell carcinoma of the skin who are eligible. 17. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), human immunodeficiency virus (HIV) antibody/antigen at Screening. 18. Has poor peripheral venous access. 19. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 3 months prior to Day 1. 20. Has a Screening or Day 1 of Period 1 abnormal (clinically significant) electrocardiogram (ECG). Entry of any participant with an abnormal (not clinically significant) ECG must be approved, and documented by signature by the principal investigator. 21. Has abnormal Screening or Day 1 of Period 1 laboratory values that suggest a clinically significant underlying disease or participant with the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.5 the upper limits of normal. 22. Has abnormal Screening or Day 1 of Period 1 vital sign values that suggest a clinically significant underlying disease. 23. Has a risk of suicide according to the Investigator's clinical judgment (eg, per Columbia-Suicide Severity Rating Scale [C-SSRS] or has made a suicide attempt within 6 months prior to screening visit). 24. Has a current diagnosis of a significant psychiatric illness other than schizophrenia, per DSM-V and is in an acute phase/episode. 25. In the opinion of the investigator or sponsor, the participant is unsuitable for inclusion in the study. | |
| 74 | NCT02079870 | completed | 0.6115871667861938 | phase 1 | ['diabetes', 'metabolism and nutrition disorder', 'obesity'] | ["['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']", "['E70.5', 'E71.32', 'E72.4', 'E76.9', 'E78.89', 'E83.2', 'E88.40']", "['E66.8', 'E66.9', 'E66.1', 'O99.214', 'O99.215', 'O99.210', 'O99.211']"] | ['semaglutide', 'placebo'] | ['CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)CC1=CNC=N1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Male or female, age above or equal to 18 years at the time of signing informed consent - HbA1c (glycosylated haemoglobin A1c) below 6.5% - A BMI (body mass index) between 30-45 kg/m^2 (both inclusive) Exclusion Criteria: - Females who are pregnant, breast-feeding or intend to become pregnant or is of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local law or practice, UK requirements: adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods together with the use of spermicide, and sexual abstinence) - Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Diagnosis of type 1 or 2 diabetes mellitus - Anticipated change in lifestyle (e.g. eating, exercise or sleeping pattern) during the trial - Use of any prescription or non-prescription medication which could interfere with trial pharmacokinetic or pharmacodynamic results, as judged by the investigator or specifically: 1) within 12 months prior to screening any weight lowering pharmacotherapy or pharmacotherapy that may cause weight gain, including systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers, 2) within 3 months prior to screening use of statins, antihyperlipidemics including fibrates or nicotinic acid and its derivates, 3) supplementation with omega 3 fatty acids from 1 month prior to screening, 4) co-treatment with antihypertensive drugs is allowed if treatment has been stable for at least 1 month prior to screening and treatment should be kept unchanged during the trial - Significant history of alcoholism or drug/chemical abuse within 1 year from screening, or a positive result of the urine drug screen or alcohol breath test, or consuming more than 21 units of alcohol per week for females and 28 units of alcohol per week for males (1 unit of alcohol equals ½ pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits) - Smoking or use of any nicotine products (including nicotine patches, gum etc.) in the last 3 months prior to screening or a positive cotinine test | |
| 75 | NCT02080195 | terminated | study was unable to accrue subjects | 0.4885404109954834 | phase 1/phase 2 | ['lupus erythematosus', 'graft-versus-host disease'] | ["['D89.810', 'D89.811', 'D89.813', 'D89.812']"] | ['cyclophosphamide', 'fludarabine', 'tacrolimus', 'mycophenolate mofetil', 'rabbit antithymocyte globulin'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'ClCCN(CCCl)P1(=O)NCCCO1', 'COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: - Four or more American College of Rheumatology (ACR) criteria for the classification of SLE or 4 or more of the SLICE criteria - Involvement of one or more of the following organ systems: renal, neurologic, hematologic, cardiac, pulmonary, gastrointestinal - A lack of response to corticosteroids in moderate-to-high doses, and to either an equivalent degree of immunosuppression with azathioprine, methotrexate, cyclosporin, tacrolimus, belimumab, rituximab, mycophenolate mofetil, and/or appropriate other treatment - Patients should be eligible for transplantation according to the BMT Policy Manual Exclusion Criteria: - Age less than 18 years and over 75 years - Any risk of pregnancy - Patients who are preterminal or moribund |
| 76 | NCT02080416 | terminated | very slow accrual; terminated to allow resources to be utilized more effectively on other studies. no data analysis completed, nor any conclusions reached. | 0.6524413228034973 | early phase 1 | ['non-hodgkin lymphoma', 'hodgkin lymphoma', 'kaposi sarcoma', 'gastric cancer', 'nasopharyngeal cancer', 'ebv', 'castleman disease'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C46.9', 'C46.0', 'C46.2', 'C46.1', 'C46.3', 'C46.4', 'C46.50']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['A36.1', 'B87.3']", "['D47.Z2']"] | ['nelfinavir'] | ['[H][C@@]12CCCC[C@]1([H])CN(C[C@@H](O)[C@H](CSC1=CC=CC=C1)NC(=O)C1=C(C)C(O)=CC=C1)[C@@H](C2)C(=O)NC(C)(C)C'] | Inclusion Criteria: - Age 18 years or older - Biopsy proven EBV(+) or KSHV(+) malignancy - Relapsed/refractory disease failing > 2 prior therapies - Measurable, non-bony disease (at least one lesion on radiographic or physical exam assessment measuring > 2 cm in longest axis) - KS patients with skin-only disease must have cutaneous lesions amenable to four 3 mm punch biopsies during the course of the study - Eastern Cooperative Oncology Group (ECOG) performance status < 2 - Life expectancy of greater than 12 weeks - Patients must be able to lie flat for at least 60 minutes and fit on a PET-CT scanner - Ability to comply with an oral drug regimen - Females of childbearing potential must have a negative pregnancy test at screening - Patients must have normal organ and marrow function as defined below within 14 days of study entry Exclusion Criteria: - Patients with HIV-associated primary central nervous system lymphoma - Radiotherapy or chemotherapy ending within 14 days of study enrollment - Patients currently on other protease inhibitors - Chronic diarrhea - Acute, active infection within 14 days of enrollment - Patients on active treatment for hypo- or hyperthyroidism - End-stage liver disease unrelated to tumor - Hepatitis B or hepatitis C infection - Use of any other type of investigational agent or treatment concurrently or within 28 days before the first dose of study treatment - History of iodine hypersensitivity - Females who are pregnant or breastfeeding - Physical or psychiatric conditions that in the estimation of the investigator place the patient at high risk of toxicity, non-compliance, or inability to complete the study requirements - Use of drugs to treat or prevent herpesvirus infections - Essential medication that is known to interact with nelfinavir |
| 77 | NCT02083536 | withdrawn | study voluntarily stopped by principal investigator due to lack of accrual. | 0.46403440833091736 | phase 1 | ['ovarian cancer', 'ovarian carcinoma', 'recurrent ovarian cancer', 'recurrent ovarian carcinoma'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['docetaxel'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - 1. Patients must have platinum-resistant disease relapsing within 6 months or less from the date of their last cycle of initial adjuvant chemotherapy recurrent adenocarcinoma from a primary ovarian, tubal, or peritoneal cancer following first-line chemotherapy for metastatic disease. There is no limit on prior number of chemotherapy regimens. Patients who have received prior systemic docetaxel and platinum-based chemotherapy are eligible - 1.1 Patients must have ≥ 1cm measurable disease on imaging studies independent of patients having an optional surgical salvage procedure. - 2. Patients must have a life expectancy of at least 6 months. - 3. Patients must have Karnofsky performance status of ≥ 60 or Gynecology Oncology (GOG) performance status of ≤ 2 (see www.GOG.org website). - 4. Age 18 - 80 years old - 5. Patients must have an adequate bone marrow, renal, and hepatic function: - 5.1 WBC: ≥ 3,000 /mcl - 5.2 ANC: ≥ 1,500 /mcl - 5.3 Platelets: ≥ 100,000 /mcl - 5.4 Creatinine: < 2.0 mg/dcl - 5.5 Bilirubin: < 1.5x institutional normal value - 5.6 LDH, GGT, SGPT (ALT), SGOT (AST), and ALK Phos:< 3x institutional normal value. - 6. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: - 1. Patients who have received prior radiotherapy to the chest, whole abdomen, or lower extremities above the knees. - 2. Patients who have received prior radiation therapy to the head, neck, or lower extremities below the knees if greater than 3 years prior to study entry. - 3. Evidence of extra-abdominal extension of disease (such as groin nodes, lung, supraclavicular nodes, and pleural fluid). - 4. Patients may not be receiving any other investigational agents within 4 weeks preceding the start of study treatment) or chemotherapy for at least 3 weeks preceding the start of study treatment. - 5. Patients who have been diagnosed with another prior malignant tumor within 3 years of study entry, excluding non-melanoma skin cancer and carcinoma in situ of the cervix. - 6. Patients with prior history of a severe hypersensitivity reaction to paclitaxel (polysorbate 80-Cremophor). - 7. Patients with current history of uncontrolled hypertension, angina pectoris, heart failure, cardiac dysrhythmias, pericardial disease, cardiomyopathy, or active infection. - 8. Presence of any medical condition that in the opinion of the investigator deems the patient unable to participate. - 9. Females of child-bearing potential. It is expected that ovarian cancer patients would have had a hysterectomy and/or oophorectomy as part of the original standard of care. - 10. Patients that are < 18 yrs. of age or > 80 yrs. of age. |
| 78 | NCT02083926 | unknown status | 0.49759867787361145 | early phase 1 | ['social anxiety disorder'] | ["['F20.81', 'F21', 'F34.0', 'F34.1', 'F42.3', 'F45.0', 'F51.5']"] | ['ketamine', 'saline'] | ['CC1=CC(O)=CC(C)=C1Cl', 'COCCC1=CC=C(OCC(O)CNC(C)C)C=C1'] | Inclusion Criteria: 1. Adult between the ages of 18 and 65 years 2. Meet DSM IV criteria for Social Anxiety Disorder by structured clinical interview (SCID) and have a LSAS >60 with or without co-morbid MDD Exclusion Criteria: 1. Positive pregnancy test 2. History of substance abuse disorder within the last 6 months or positive urine toxicology on screening (within the previous 6 months). 3. History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR criteria 4. Medical comorbidity that significantly increases the risks associated with ketamine infusion (e.g. untreated hypertension, significant cardiovascular disease) | |
| 79 | NCT02086513 | terminated | 0.4892926812171936 | phase 1 | ['graft versus host disease'] | ["['D89.810', 'D89.811', 'D89.813', 'D89.812']"] | ['lde225'] | ['[H][C@]1(C)CN(C[C@@]([H])(C)O1)C1=CC=C(NC(=O)C2=CC=CC(=C2C)C2=CC=C(OC(F)(F)F)C=C2)C=N1'] | Inclusion Criteria: Patients eligible for inclusion in this study have to meet all of the following criteria: - Patients must provide written informed consent prior to any screening procedures. - Age 18 years or older. - Recipients of allogeneic hematopoietic cell transplantation (HCT) after either myeloablative or reduced intensity conditioning regimens. Any donor source of stem cells is eligible. - Participants must be at least 100 days after HCT. - Patients must have steroid refractory classic cutaneous, myofascial, or sclerodermatous cGVHD (+/- other organ involvement, clinically diagnosed), defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at ≥ 0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms or if not improving on any line of therapy beyond steroids or if treating physician feels that increasing or adding steroids is not in the patient's best interests. Note that the dose of systemic steroids can certainly be lower than 0.25 mg/kg/day at enrollment. - Stable dose of corticosteroids for 4 weeks prior to enrollment - No addition or subtraction of other immunosuppressive medications (e.g., calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug - ECOG performance status ≤ 3 - Serum Cr ≤ 2 gm / dL - Adequate hepatic function (total bilirubin < 2.0 mg/dl, AST < 5x ULN), unless hepatic dysfunction is a manifestation of cGVHD. For patients in whom a diagnosis of hemolysis or Gilbert's is made, the total bilirubin is allowed to be elevated. For patients with abnormal LFTs above the thresholds, documented cGVHD on liver biopsy will be required prior to enrollment. - Patients must have adequate bone marrow function as defined by ANC ≥ 1000 / µl and platelets ≥ 20,000 / µl without growth factor or transfusional support - Plasma creatine phosphokinase (CK) < 1.5 x ULN - Patient is able to swallow and retain oral medication Exclusion Criteria: - Patients who have had major surgery within 4 weeks of initiation of study medication. - Patients with concurrent uncontrolled medical conditions that may interfere with their participation in the study or potentially affect the interpretation of the study data. - Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndromes. - Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors. - Patients who have neuromuscular disorders (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy) or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil, and that cannot be discontinued at least 2 weeks prior to starting LDE225 treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution. - Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided whilst on LDE225 treatment. - Patients who have taken part in an experimental drug study within 4 weeks or 5 half-lives, whichever is longer, of initiating treatment with LDE225. - Patients who are receiving other anti-neoplastic therapy (e.g. chemotherapy, targeted therapy or radiotherapy) concurrently or within 2 weeks of starting treatment with LDE225. - Patients who are receiving treatment with medications known to be strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have a narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A/5 inducers for at least 2 weeks prior to starting treatment with LDE225. Note that patients who require antifungal prophylaxis are preferred to be on fluconazole, and, patients taking voriconazole or posaconazole who must continue are excluded from the dose escalation phase of the study. Once the MTD is established, patients taking voriconazole or posaconazole will be allowed to enroll but at a dose adjustment to be determined before the expansion phase opens. - Ongoing prednisone requirement > 1 mg/kg/day (or equivalent) - Exposure to any new immunosuppressive medication in the 4 weeks prior to enrollment. - ECP therapy within 4 weeks prior to enrollment - Active disease relapse - Active, uncontrolled infection - Impaired cardiac function or clinically significant heart disease, including any one of the following: - Angina pectoris within 3 months - Acute myocardial infarction within 3 months - QTc > 450 msec for males and > 470 msec for females on the screening ECG - A past medical history of clinically significant ECG abnormalities or a family history of prolonged QT-interval syndrome - Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor adherence with an antihypertensive regimen) - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL). - Patients who are not willing to apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment. - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through 6 months after the final dose of study treatment. Highly effective contraception is defined as either: - Total abstinence: When this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. - Sterilization: Patient has had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. - Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). [For female study patients, the vasectomized male partner should be the sole partner for that patient] - Use a combination of the following (both a+b): - Placement of a non-hormonal intrauterine device (IUD) or non-hormonal intrauterine system (IUS) - Barrier method of contraception: Condom or Occlusive cap (diaphragm or cervical vault caps) with spermicidal foam/gel/film/cream/vaginal suppository. - Note: Hormonal contraception methods (e.g. oral, injected, implanted) are not allowed to count as contraception as it cannot be ruled out that the study drug decreases the effectiveness of hormonal contraception. Patients are able to continue taking oral contraceptives if desired. - Note: Woman are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential - Male patient must use highly effective (double barrier) methods of contraception (e.g., spermicidal gel plus condom) for the entire duration of the study, and continue using contraception and refrain from fathering a child for 6 months following the study drug. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner in order to prevent delivery of the study treatment via seminal fluid - Sexually active males who are unwilling to use a condom during intercourse while taking the study drug and for 6 months after stopping investigational medications and agree not to father a child in this period. - Patients unwilling or unable to comply with the protocol. | |
| 80 | NCT02092363 | completed | 0.5893769264221191 | phase 1 | ['ovarian cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['omp-54f28, paclitaxel and carboplatin'] | ['[H][N]([H])([H])[Pt]1(OC(=O)C2(CCC2)C(=O)O1)[N]([H])([H])[H]'] | Inclusion Criteria: - Signed Informed Consent Form - Age ≥18 years - Histologically documented ovarian, primary peritoneal or fallopian tube cancer - Recurrent platinum-sensitive disease, defined as disease progression ≥6 months after completing a minimum of 4 cycles of a platinum-containing regimen - Availability of FFPE tumor tissue, either archival or obtained at study entry through fresh biopsy o Tumor tissue from fine needle aspiration is not acceptable. - ECOG performance status of 0 or 1 - All acute treatment-related toxicity from prior therapy must have resolved to Grade ≤ 1 prior to study entry - Adequate hematologic and end-organ function - Evaluable or measurable disease per RECIST v1.1 - For women of childbearing potential, agreement to use two effective forms of contraception Exclusion Criteria: - Non-epithelial ovarian carcinoma, including malignant mixed Mullerian tumors - Prior treatment with paclitaxel and carboplatin for recurrent platinum-sensitive ovarian cancer - Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy, or herbal therapy within 3 weeks or 5 half-lives (for systemic agents), whichever is shorter - Known hypersensitivity to any component of study treatments that resulted in drug discontinuation - Grade ≥ 2 sensory neuropathy - Uncontrolled seizure disorder or active neurologic disease - Untreated brain metastases - Leptomeningeal disease as a manifestation of cancer - Active infection requiring antibiotics - Bisphosphonate therapy for symptomatic hypercalcemia - Known history of clinically significant liver disease, including active viral hepatitis and cirrhosis - Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements - Pregnancy, lactation, or breastfeeding - Known HIV infection - Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) - Concurrent use of therapeutic warfarin - New York Heart Association Classification III or IV - Known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of study treatment or anticipation of need for major surgical procedure during the course of the study - Osteoporosis based on a T-score of <-2.5 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by DEXA scan - Bone metastases and one of the following: - Prior history of a pathologic fracture - Lytic lesion requiring an impending orthopedic intervention - Lack of treatment with a bisphosphonate or denosumab - Treatment with a thiazolidinedione PPAR gamma inhibitor; e.g. Actos® (pioglitazone) and Avandia® (rosiglitzone) - Active treatment with an oral or IV glucocortocoid for ≥4 weeks at a daily dose equivalent to or greater than 7.5 mg of oral prednisone - Fasting β-CTX of >1000 pg/mL - Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia | |
| 81 | NCT02096042 | terminated | slow accrual. | 0.5397400259971619 | phase 1/phase 2 | ['leukemia'] | ["['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']"] | ['brentuximab vedotin', '5-azacytidine'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O'] | Inclusion Criteria: 1. Histologically or cytologically confirmed AML, other than acute promyelocytic leukemia, as defined by the 2008 World Health Organization (WHO) criteria that is relapsed or refractory to standard chemotherapy. Note: Newly-diagnosed AML patients who are 60 years or older and are not candidates for or have refused standard chemotherapy are also eligible for this trial. 2. AML blasts must express CD30 (>/=10% expression as assessed by flow-cytometry or 2+ expression by immunohistochemistry) (whenever possible CD30 expression will be assessed by both methods) 3. Age 18 years or older 4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of </=3 5. The following baseline laboratory data: Serum bilirubin </=1.5 x upper limit of normal (ULN) or </= 3 x ULN for patients with Gilbert's disease; Serum creatinine </=1.5 x ULN AND creatinine clearance >30 ml/min; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </=3 x ULN 6. Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (beta-hCG) pregnancy test result within 14 days prior to the first dose of brentuximab vedotin and must agree to use an effective contraception method during the study and for 30 days following the last dose of study drug. Females of non- childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy. 7. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug 8. Patients or their legally authorized representative must provide written informed consent. Exclusion Criteria: 1. History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses). 2. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association Class III-IV within 6 months prior to their first dose of brentuximab vedotin 3. Evidence of active cerebral/meningeal disease. Patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of registration. 4. Previous treatment with any anti-CD30 directed therapy 5. Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: <100 days from allogeneic SCT, Acute or chronic graft-versus-host disease (GvHD), or Receiving immunosuppressive therapy as treatment for or prophylaxis against GvHD within the last 7 days 6. Patients with uncontrolled active infections (viral, bacterial, and fungal) are not eligible. 7. Known to be positive for hepatitis B by surface antigen expression 8. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months) 9. Preexisting grade >/=2 peripheral neuropathy 10. Patients with uncontrolled diabetes mellitus 11. Current therapy with other systemic anti-neoplastic or anti-neoplastic investigational agents. 12. Chemotherapy (except hydroxyurea or emergent use of single-agent cytarabine for cytoreduction), radiotherapy, biologics, and/or other treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug, unless progressive disease is documented. NOTE: Hydroxyurea will be allowed during the first cycle of treatment 13. Females who are pregnant or lactating 14. Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin 15. History of progressive multifocal leukoencephalopathy (PML) |
| 82 | NCT02096601 | completed | 0.8729394674301147 | phase 1/phase 2 | ["parkinson's disease"] | ["['G20']"] | ['levodopa and carbidopa sc solution', 'oral levodopa and carbidopa'] | ['N[C@@H](CC1=CC(O)=C(O)C=C1)C(O)=O', 'C[C@@](CC1=CC(O)=C(O)C=C1)(NN)C(O)=O'] | Inclusion Criteria: 1. Male and female PD patients of any race aged 30 to 80 years 2. PD diagnosis consistent with the UK PD Society Brain Bank criteria. 3. Stable doses of anti PD drugs for at least 30 days 4. PD patients with well-defined morning "OFF" and a good response to LD 5. MMSE score > 26 6. No clinically significant medical, psychiatric or laboratory abnormalities Exclusion Criteria: 1. Atypical or secondary Parkinsonism. 2. Acute psychosis or hallucinations. 3. Subjects treated with neuroleptics 4. History of melanoma or significant skin disorders. 5. Prior neurosurgical procedure for PD. 6. Patients with a history of drug abuse or alcoholism 7. Clinically significant ECG abnormalities. 8. Renal or liver dysfunction 9. Subjects who have participated in another clinical study within 30 days | |
| 83 | NCT02098629 | withdrawn | difficulty in enrollment | 0.4968985915184021 | phase 1/phase 2 | ['myocardial reperfusion injury'] | ["['I51.5', 'I25.2', 'I25.6', 'I21.9', 'I21.A1', 'I21.A9', 'P29.4']"] | ['milrinone', 'esmolol', 'saline infusion'] | ['CC1=C(C=C(C#N)C(=O)N1)C1=CC=NC=C1', 'COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1', '[Na+].[Cl-]'] | Inclusion Criteria: - Men and women, 18 years of age or older, who present within 12 hours after the onset of chest pain, who has ST-segment elevation of more than 0.1 mV in two contiguous leads, and for whom the clinical decision is made to treat with PCI will be eligible for enrollment. Exclusion Criteria: - Patients with cardiac arrest, ventricular fibrillation, cardiogenic shock, previous acute myocardial infarction will not included in the study. Patients with occlusion of the left main will be excluded. Patients with baseline heart rate <50 beats/min and systolic BP<90 mmHg and pregnant patients will excluded. Finally, patients who have any disorder that is associated with immunologic dysfunction (e.g., cancer, lymphoma, a positive serologic test for the human immunodeficiency virus, or hepatitis) more recently than 6 months before presentation will be excluded. |
| 84 | NCT02100657 | completed | 0.6845042705535889 | phase 1 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['plitidepsin', 'bortezomib', 'dexamethasone'] | ['[H][C@@]12CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)C(=O)[C@@H](OC(=O)C[C@H](O)[C@]([H])(NC(=O)[C@@H](NC(=O)[C@@H](CC(C)C)N(C)C(=O)[C@@H]1CCCN1C(=O)C(C)=O)[C@@H](C)OC(=O)[C@H](CC1=CC=C(OC)C=C1)N(C)C2=O)[C@@H](C)CC)C(C)C', 'ClCCN(CCCl)P1(=O)NCCCO1', 'C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F'] | Inclusion Criteria: - Age ≥ 18 years. - Prior autologous transplantation (HSCT) patients are allowed. - Patients must have received at least one previous treatment line of induction, chemotherapy, chemotherapy and transplantation or previous treatment with bortezomib or another proteasome drug Exclusion Criteria: - Previous treatment with plitidepsin. - Active or metastatic primary malignancy other than MM. - Serious concomitant systemic disorders - History of hypersensitivity reactions to bortezomib, polyoxyl 35 castor oil or mannitol - Neuropathy - Pregnant and/or lactating women - HIV infection - Active hepatitis B or C virus infection. - Treatment with any Investigational Medicinal Product (IMP) in the 30 days before inclusion in the study - Plasma cell leukemia at the time of study entry - Contraindication for the use of steroids | |
| 85 | NCT02100852 | completed | 0.5018333196640015 | phase 1 | ['chronic lymphocytic leukemia'] | ["['C91.11', 'C91.12', 'C91.10']"] | ['tgr-1202 + obinutuzumab + chlorambucil'] | ['OC(=O)CCCC1=CC=C(C=C1)N(CCCl)CCCl'] | Inclusion Criteria: - Confirmed Chronic Lymphocytic Leukemia (CLL) - Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 - Ability to swallow oral medication Exclusion Criteria: - Known hepatitis B virus, hepatitis C virus or HIV infection - Primary central nervous system lymphoma or known intracranial involvement - Autologous hematologic stem cell transplant within 3 months of study entry or Allogeneic hematologic stem cell transplant within 12 months | |
| 86 | NCT02103335 | completed | 0.6056219935417175 | phase 1 | ['multiple myeloma in relapse', 'refractory multiple myeloma', 'multiple myeloma'] | ["['C90.02']", "['D46.4', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21', 'D46.22']", "['C90.01', 'C90.02', 'C90.00']"] | ['pomalidomide', 'marizomib', 'low-dose dexamethasone'] | ['[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C', 'C[C@@]12OC(=O)[C@@]1(NC(=O)[C@@H]2CCCl)[C@@H](O)[C@H]1CCCC=C1', '[H][C@@]12C[C@@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C'] | Inclusion Criteria Subjects must meet the following criteria to be eligible for study participation: 1. At least 18 years at the time of signing the informed consent form. 2. Able to understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Documented diagnosis of multiple myeloma and measurable disease by serum or urine protein electrophoresis (SPEP or UPEP): SPEP ≥0.5 g/dL, UPEP ≥200 mg/24 hours, or involved serum free light chain (FLC) level ≥10 mg/dL provided the serum FLC ratio is abnormal. 5. Previously received 1 or more lines of anti-myeloma therapy that must have included both lenalidomide and bortezomib (either separately or in combination). 6. Documented disease progression during or within 60 days after their most recent line of anti myeloma therapy. 7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2. 8. All study participants in the USA must be registered into the mandatory POMALYST REMS™ (Risk Evaluation & Mitigation Strategy) program, and be willing and able to comply with the requirements of the POMALYST REMS™ program. 9. All study participants in the USA who are females of child-bearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the POMALYST REMS™ program. 10. All study participants outside the USA must agree to comply with the POMALYST® PPRMP requirements. 11. All subjects must be able and agree to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin). 12. For females of child bearing potential (FCBP): Agree to use 2 reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study treatment, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation; must follow pregnancy testing requirements as outlined in the POMALYST REMS™ program or the PPRMP. 13. For all females: Agree to abstain from breastfeeding during study participation and for at least 28 days after study treatment discontinuation. 14. For all males: Agree to use a latex or synthetic condom during any sexual contact with FCBP while participating in the study and for at least 28 days following discontinuation from study treatment, even if he has undergone a successful vasectomy. 15. For all males: Agree to refrain from donating semen or sperm while on study and for at least 28 days after discontinuation from study treatment. 16. Refrain from donating blood while on study treatment and for at least 28 days after discontinuation from study treatment. 17. Agree not to share medication. Exclusion Criteria Subjects with any of the following will be excluded from participation in the study: 1. Peripheral neuropathy Grade ≥2. 2. Non-secretory multiple myeloma. 3. Any of the following laboratory abnormalities: - ANC <1,000/µL; - Platelet count <50,000/µL for subjects in whom <50% of bone marrow nucleated cells are plasma cells; or a platelet count <30,000/µL for subjects in whom ≥50% of bone marrow nucleated cells are plasma cells; - Creatinine clearance (CrCL) <45 mL/min as measured directly or as calculated according to Cockcroft Gault formula; - Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L); - Hemoglobin <8 g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted before study entry); - Serum aspartate aminotransferase (AST) >3.0 x upper limit of normal (ULN); - Serum alanine aminotransferase (ALT) >3.0 x ULN; - Serum total bilirubin >1.5 x ULN (>3.0 x ULN for subjects with known Gilbert's disease). 4. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥5 years. Subjects may be entered earlier than 5 years if they have received curative treatment for the following: - Basal cell carcinoma of the skin; - Squamous cell carcinoma of the skin; - Carcinoma in situ of the cervix; - Carcinoma in situ of the breast; Or if they have: o Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or non metastatic prostate cancer that is in complete remission or does not require treatment. 5. Previous therapy with POM and/or MRZ. 6. History of allergic reaction or hypersensitivity to thalidomide, lenalidomide, bortezomib, carfilzomib, boron, mannitol, or DEX. 7. Grade ≥3 rash during prior thalidomide or lenalidomide therapy. 8. Gastrointestinal disease that may significantly alter the absorption of POM. 9. History of the following: - Congestive heart failure of Class III or IV of the New York Heart Association (NYHA) classification; - Myocardial infarction within 12 months prior to starting study treatment; - Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris. 10. Any of the following within 14 days prior to initiation of study treatment: - Plasmapheresis; - Major surgery (kyphoplasty is not considered major surgery); - Radiation therapy; - Anti-myeloma drug therapy. 11. Received any investigational agents within 28 days or 5 half-lives (whichever is longer) prior to initiation of study treatment. 12. Conditions requiring chronic steroid or immunosuppressive treatment (eg, rheumatoid arthritis, multiple sclerosis, or lupus), which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. 13. Subjects may not receive corticosteroids (>10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment (use of steroidal inhalation aerosol for asthma is permitted). 14. Unable or unwilling to undergo antithrombotic prophylactic treatment. 15. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, as determined by the Investigator. 16. Pregnant and/or breastfeeding females. 17. Known seropositive for or active viral infection with human immunodeficiency virus (HIV). 18. Known seropositive for or active viral infection with hepatitis B virus (HBV), with the following exceptions: - negative are eligible. - Subjects who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible. - Subjects who are seropositive because of hepatitis B virus vaccine are eligible. 19. Known seropositive for or active viral infection with hepatitis C virus (HCV), with the following exception: Subjects who had hepatitis C but have received an antiviral treatment and show no detectable viral ribonucleic acid (RNA) for 6 months are eligible. | |
| 87 | NCT02106897 | completed | 0.5887895822525024 | phase 1 | ['systemic lupus erythematosus', 'healthy volunteers'] | ["['M32.9', 'M32.0', 'M32.11', 'M32.12', 'M32.13', 'M32.14', 'M32.8']"] | ['biib059', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Part 1: Key Inclusion Criteria For Healthy Volunteers: - Be in good health as determined by the Investigator, based on medical history, physical examination, and 12-lead ECG. - Body mass index (BMI) between 18 and 30 kg/m2 and body weight ≥45 kg. Part 1: Key Exclusion Criteria For Healthy Volunteers: - History of or positive test results at screening for the following: for human immunodeficiency virus (HIV), hepatitis C virus antibody (HCV Ab), hepatitis B virus (defined as positive for hepatitis B surface antigen [HBsAg] or hepatitis B core antibody [HBcAb]). - - History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization. - History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug. - History of any clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator. - Any live or attenuated immunization/vaccination within 1 month prior to randomization or planned to occur during the study period. - Blood donation (1 unit or more) within 1 month prior to randomization. - Vigorous exercise (e.g., jogging, swimming laps, heavy gardening, hiking uphill, etc.) within 48 hours prior to Day -1 Part II: Key Inclusion Criteria for SLE Participants: - Definite SLE for at least 6 months duration or anti-dsDNA antibody, prior to screening. - Presence of active lupus skin disease including acute, sub acute, and/or chronic cutaneous lupus (e.g., discoid) at the time of screening and randomization. - BMI between 18 and <40 kg/m2 and body weight ≥45 kg. Part II: Key Exclusion Criteria for SLE Participants: - Active neuropsychiatric SLE including but not limited to the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes. - History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization. - Symptoms of bacterial or viral infection (including upper respiratory tract infection) within 28 days prior to randomization. - History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug. - Evidence of skin conditions other than lupus skin disease (e.g., eczema) at screening or at the time of randomization that would interfere with evaluations of the effect of study treatment on lupus skin disease. - Treatment with oral prednisone >15 mg daily (or equivalent). Any prednisone regimen must be stable for at least 28 days before randomization and expected to remain stable for the duration of the study. - Treatment with any antibiotics within 14 days prior to randomization. Part IIIa: Key Inclusion Criteria for Healthy Volunteers : - Must be in good health as determined by the Investigator, based on medical history, physical examination, and 12-lead ECG. - Must have a body mass index (BMI) between 18 and 30 kg/m2 and body weight ≥45 kg. Part IIIa: Key Exclusion Criteria for Healthy Volunteers: - History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization - History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study treatment. - Treatment with any antibiotics within 14 days prior to randomization. Part IIIb: Key Inclusion Criteria for SLE Participants: - Definite SLE for at least 6 months duration prior to screening - Presence of active lupus skin disease including acute, subacute, and/or chronic cutaneous lupus (e.g., discoid), and/or hypocomplementemia , and/or positive anti-dsDNA antibody at the time of screening. - Must have a BMI between 18 and <40 kg/m2 and body weight ≥45 kg. Part IIIb: Key Exclusion Criteria for SLE Participants: - Active neuropsychiatric SLE including but not limited to the following: seizure, new or worsening impaired level of consciousness, psychosis, delirium or confusional state, aseptic meningitis, ascending or transverse myelitis, chorea, cerebellar ataxia, mononeuritis multiplex, or demyelinating syndromes. - History of chronic, recurrent, or recent serious infection (e.g., pneumonia, septicemia) as determined by the Investigator within 3 months prior to screening and randomization. - History of severe allergic or anaphylactic reactions or history of allergic reactions likely to be exacerbated by any component of the study drug. - Treatment with any antibiotics within 14 days prior to randomization. NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply | |
| 88 | NCT02109224 | terminated | inadequate accrual rate | 0.6490576267242432 | phase 1 | ['adult b acute lymphoblastic leukemia', 'chronic lymphocytic leukemia', 'cutaneous b-cell non-hodgkin lymphoma', 'extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue', 'hiv infection', 'intraocular lymphoma', 'multicentric angiofollicular lymphoid hyperplasia', 'nodal marginal zone lymphoma', 'recurrent adult acute lymphoblastic leukemia', 'recurrent adult burkitt lymphoma', 'recurrent adult diffuse large cell lymphoma', 'recurrent adult diffuse mixed cell lymphoma', 'recurrent adult diffuse small cleaved cell lymphoma', 'recurrent adult grade iii lymphomatoid granulomatosis', 'recurrent adult immunoblastic lymphoma', 'recurrent adult lymphoblastic lymphoma', 'recurrent grade 1 follicular lymphoma', 'recurrent grade 2 follicular lymphoma', 'recurrent grade 3 follicular lymphoma', 'recurrent mantle cell lymphoma', 'recurrent marginal zone lymphoma', 'recurrent small lymphocytic lymphoma', 'refractory chronic lymphocytic leukemia', 'refractory hairy cell leukemia', 'refractory plasma cell myeloma', 'small intestinal lymphoma', 'splenic marginal zone lymphoma', 'testicular lymphoma', 'waldenstrom macroglobulinemia'] | ["['C83.57', 'C83.50', 'C91.01', 'C91.02', 'C83.52', 'C83.56', 'C83.53']", "['C91.11', 'C91.12', 'C91.10']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['Z21']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['M26.01', 'M26.03', 'K38.0', 'M26.71', 'M26.72', 'N85.00', 'N85.01']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C83.57', 'C83.50', 'C91.01', 'C91.02', 'C83.52', 'C83.56', 'C83.53']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['A87.2', 'K52.832', 'D72.111', 'C91.11', 'C91.12', 'C91.10']", "['D46.4', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21', 'D46.22']", "['D46.4', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21', 'D46.22']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C88.0']"] | ['ibrutinib'] | ['NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1'] | Inclusion Criteria: - Known HIV infection and histologically confirmed B-cell non-Hodgkin lymphoma or B-cell lymphoproliferative disease as follows, as defined by the World Health Organization classification: - Active B-cell non-Hodgkin lymphoma (cluster of differentiation [CD]20 positive or negative), chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), or multiple myeloma that has relapsed, progressed, or been refractory to at least one regimen - Note: Patients with CLL, SLL, or mantle cell lymphoma (MCL) may only be enrolled in Stratum C - At least 14 days between ibrutinib initiation and last cancer therapy; any number of prior cancer therapies is permitted; patients otherwise fit for blood or marrow transplantation (BMT) should receive second-line chemotherapy before considering enrollment - Serologic documentation of HIV infection at any time prior to study entry, as evidenced by positive enzyme-linked immunosorbent assay (ELISA), positive Western blot, or any other federally approved licensed HIV test; alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and Western blot, or other approved diagnostic tests - Participants must be on a stable antiretroviral regimen per current International Acquired Immunodeficiency Syndrome (AIDS) Society guidelines as follows, with no intention of changing the regimen within 8 weeks after ibrutinib initiation: - Choice of regimen: The specific antiretroviral agents are at physician discretion, and the use of investigational agents currently available on an expanded-access basis is allowed; use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) is prohibited - Patients with mantle cell lymphoma, CLL, or SLL must be on non-cytochrome P450, family 3, subfamily A, polypeptide 4 (CYPA3A4) modulating antiretroviral agents (Stratum C) to be eligible for this study - Patients may be switched to non-conflicting regimens in order to participate - Stability of regimen: With the exception of patients on zidovudine-based ART, any changes in antiretroviral regimen must be made at least 4 weeks prior to ibrutinib initiation; patients taking zidovudine-based ART must change to a non-zidovudine-based regimen at least 2 weeks prior to ibrutinib initiation; changes to ART therapy during the study may be made if medically necessary (e.g. toxicity, treatment failure) - Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2 (Karnofsky >= 60%) - Life expectancy >= 2 months - Absolute CD4+ lymphocyte count: >= 75 cells/uL - Absolute neutrophil count >= 750 cells/uL - Platelets >= 50,000 cells/uL, or >= 30,000/uL if bone marrow is involved by malignancy - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional upper limit of normal (ULN), or =< 5.0 x ULN if attributable to malignancy - Total bilirubin =< 2.0 x ULN, unless elevated bilirubin is attributable to Gilbert's syndrome or to HIV medications (e.g., indinavir, tenofovir, atazanavir) - Creatinine clearance (CrCl) >= 40 mL/min (modified Cockcroft-Gault) - All subjects must be screened for hepatitis B and C infection; subjects must either have no history of hepatitis B or C, or must meet the following criteria in order to e eligible: - Hepatitis B: Subjects infected with hepatitis B must receive anti-hepatitis B therapy; per Infectious Diseases Society of America (IDSA) and American Association for the Study of Liver Diseases (AASLD) guidelines, subjects that show no immunity, defined by the lack of hepatitis B surface antibody, and show evidence of chronic infection (i.e. hepatitis B surface antigen positive [HBsAg+], hepatitis B core antibody positive [HB core AB +], hepatitis B surface antibody negative [HBsAB-]) must be on anti-hepatitis B therapy throughout the study in order to be eligible; the exact hepatitis B therapy is at the discretion of the infection disease specialist or investigator; all patients diagnosed with hepatitis B must also meet the liver function test criteria listed above and have no evidence of cirrhosis; however, all patients who present with acute hepatitis B, or who show normal transaminases but are HBsAg+ and immunoglobulin M positive (IgM+) for hepatitis B core antigen, are ineligible - Hepatitis C: Subjects, who are hepatitis C antibody positive, with or without a positive hepatitis C ribonucleic acid (RNA) level, must meet the liver function test criteria listed above and have no evidence of cirrhosis; patients diagnosed with hepatitis C less than 6 months before enrollment will be considered to have acute hepatitis C and will be ineligible unless the hepatitis C viral load is undetectable - Must in the opinion of the investigator be capable of complying with this protocol - Patients may not begin protocol therapy within 7 days of major surgery or within 3 days of minor surgery - Willingness of sexually active subjects to use adequate contraception; both men and women of child-bearing potential treated or enrolled on this study must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, and 4 months after completion of ibrutinib; men who only have sex with other men do not need to use contraception specifically for this study; (should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately) - Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: - Prior exposure to ibrutinib - Receipt of any investigational agents within 14 days before the first dose of ibrutinib - Failure to recover to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 2 from clinically significant toxicities due to prior cancer therapies or to any investigational agents - Active central nervous system involvement by malignancy; central nervous system disease that has been treated into remission is permitted; a chart note of the clinician's impression of lack of central nervous system (CNS) involvement is acceptable - Patients who require concomitant treatment with CYP3A4/5 strong inhibitors or inducers OTHER than antiretroviral therapies for HIV - As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter product - A prednisone equivalent of < 20 mg daily is permitted in patients requiring chronic use; larger doses must be discontinued >= 7 days prior to ibrutinib initiation and are prohibited during study treatment - Anticoagulation with warfarin or equivalent vitamin K antagonists within 28 days prior to starting ibrutinib and throughout the study - Significant or uncontrolled intercurrent condition including, but not limited to: - Infection other than HIV, hepatitis B, or hepatitis C that is symptomatic or requires systemic treatment - Opportunistic infection within 60 days prior to enrollment - Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia, congestive heart failure, any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or history of myocardial infection within 6 months prior to enrollment - History of stroke or intracranial hemorrhage within 6 months prior to enrollment - History of class B or class C cirrhosis, per the modified Child-Pugh classification - Psychiatric illness that would limit compliance - Inability to swallow capsules whole, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, small bowel resection, or poorly controlled inflammatory bowel disease affecting the small intestine - History of prior malignancy, with the exception of the following: - Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician - Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease - Adequately treated cervical carcinoma in situ without current evidence of disease - Skin-limited Kaposi sarcoma that has not required systemic treatment within 6 months prior to study enrollment - History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib - Pregnancy or breastfeeding; a pregnancy test must be performed within 7 days prior to ibrutinib initiation in women of childbearing potential; pregnant women are excluded; breastfeeding must be discontinued |
| 89 | NCT02109341 | completed | 0.35983338952064514 | phase 1/phase 2 | ['metastatic pancreatic cancer'] | ["['C25.3']"] | ['paclitaxel bound albumine'] | ['[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](OCCO)[C@@H](C1)OC'] | Inclusion Criteria: - . Males or females ≥ 18 years old and ≤ 75 years old; - Histological or cytological evidence of a diagnosis of pancreatic ductal adenocarcinoma; - Written informed consent prior to any study-specific procedures; 4. Measurable metastatic disease, defined in according to RECIST Version 1.1 (Eisenhower et al. 2009), that had not previously been treated with CT for metastatic disease; - Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 ; - Absence of previous abdominal radiotherapy on target lesions (except radiation therapy analgesic if it has not been performed on measurable targets); - Absence of heart failure or angina or infarction within 12 months previous inclusion; - Have adequate organ function including: Hematologic: absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L. Hepatic: Bilirubin ≤ 1.5 times upper limits of normal (ULN) (Pts may have endoscopic or radiologic stenting to treat biliary obstructions). Renal: Serum creatinine within normal limits ≤1.5 times ULN. Exclusion Criteria: - Age of 76 years or older; - Endocrine or acinar pancreatic carcinoma; - Previous radiotherapy for measurable lesions; - Central nervous system metastasis; - Other concomitant cancer or history of cancer outside a carcinoma in situ of the cervix or basal or squamous cell of the skin; - Pts already included in another clinical trial with other experimental drugs; - Current active infection; - Have serious pre-existing medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris, or a clinically significant history of cardiac disease or uncontrolled diabetes mellitus); - Females who are pregnant or lactating; - Unable to undergo medical test for geographical, social or psychological reason - Known dihydropyrimidine dehydrogenase (DPD) deficiency | |
| 90 | NCT02109627 | terminated | low accrual | 0.589453399181366 | phase 1 | ['acute myeloid leukemia', 'relapsed acute myeloid leukemia', 'refractory acute myeloid leukemia'] | ["['C92.A1', 'C92.A2', 'C92.61', 'C92.62', 'C92.A0', 'C92.60']", "['D46.4', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21', 'D46.22']"] | ['ficlatuzumab', 'cytarabine'] | ['ClCCN(CCCl)P1(=O)NCCCO1'] | Inclusion Criteria: - Relapsed or refractory AML as defined by one of the following criteria: 1. First relapse within 12 months after date of first Complete Response (CR) or complete repsonse with incomplete hematologic recovery (CRi) 2. Persistent AML documented by bone marrow biopsy at least 28 days after day 1 of the first induction cycle of cytotoxic chemotherapy 3. Hypercellular bone marrow with greater than 20% cellularity and 10% blasts at least 14 days after first induction cycle day 1 - Age >=18 - Prior induction therapy had to include no more than two cycles of cytotoxic chemotherapy and at least one induction cycle must have consisted of an anthracycline or anthracenedione and cytarabine combination with a reasonable schedule/dose according to the discretion of the investigator - Histologically confirmed AML by hematopathology review performed within four weeks prior to study entry - Ejection fraction >=40% by transthoracic echocardiogram or radionuclide ventriculogram, i.e. multigated acquisition (MUGA) scan - Treatment for non-hematologic malignancy greater than 6 months prior to enrollment is acceptable. - Transplantation for AML (allogeneic or autologous) allowed unless within 90 days of study entry - No active graft versus host disease (GVHD) or immunosuppression for prevention or treatment of GVHD within two weeks of study entry - Prior treatment of myelodysplastic syndrome or myeloproliferative neoplasm with hypomethylating agent acceptable. - Cytoreduction therapy with plasmapheresis or hydroxyurea acceptable. - Females must have a negative serum pregnancy test 24 hours prior to the start of treatment or be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) - Adequate liver function as defined by total bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's syndrome) and aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 times upper limit of normal, unless these are thought to be due to AML - Adequate renal function with creatinine ≤ 2.0 mg/dL - The effects of ficlatuzumab on the developing human fetus are unknown. For this reason and because cytarabine is pregnancy category D, women of child-bearing potential and men must agree to use adequate contraception: hormone, barrier method of birth control, or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and at least one month after completion of study drug administration. - Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: - Acute promyelocytic leukemia (FAB M3 AML) - More than 2 cycles of prior induction therapy for AML - Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days of study entry or on active immunosuppressive therapy for graft versus host disease (GVHD) within 2 weeks before study entry - Cytarabine containing regimen in excess of 2 g/m2/day within 6 months of study entry - Chemotherapy, radiation, or immunotherapy, within 2 weeks prior to study entry, other than those specified in the inclusion criteria (hydroxyurea and hypomethylating agents) - Known active HIV, hepatitis B or C or infection. Exception for patients with hepatitis B on antivirals and low viral load, to be determined at the discretion of the investigator. - Uncontrolled infection - Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements - Active second malignancy that in the opinion of the PI may interfere with or be adversely affected by this treatment. - Prior exposure to the investigational agent or anti-c-Met, anti-HGF or anti-VEGF directed therapy within six months prior to study entry - Prior grade 4 toxicity attributed to cytarabine - Known or suspected drug sensitivity to cytarabine or the investigational agent ficlatuzumab - Inability to provide consent - Pregnant women are excluded from this study because the effect of ficlatuzumab on the developing fetus remains unknown and that cytarabine is a pregnancy risk category D drug with known teratogenic or abortifacient effects. Because of the potential adverse events in nursing infants secondary to treatment of the mother with ficlatuzumab and cytarabine, breastfeeding should be discontinued while on study. Patients who become pregnant while on study will be removed from the study once the pregnancy is confirmed. |
| 91 | NCT02110992 | terminated | slow accrual | 0.4163692593574524 | phase 1 | ['head and neck cancer'] | ["['C76.0', 'C47.0', 'C49.0', 'C77.0', 'D17.0', 'D21.0', 'D36.11']"] | ['docetaxel'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Recurrent or second primary squamous cell head and neck cancer - Defined area of recurrence on imaging - Previous head and neck radiation (RT) to >/= 50 Gy - Performance status score 0-1 - Time interval from previous RT >/= 9 months - Volume of disease appropriate for protocol treatment - Minimum estimated survival of >/= 3 months - Age >/= 18 - Adequate labs Exclusion Criteria: - Primary tumors of the salivary gland - Original pathology report and radiation therapy records not available - Prior spinal cord dose > 45 Gy - Surgery or chemotherapy within 4 weeks - Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers are permitted |
| 92 | NCT02111551 | terminated | difficult to find participants and no funding | 0.3735440969467163 | phase 1 | ['autism'] | ["['Z13.41']"] | ['dmxb-a 150 mg', 'dmxb-a 75 mg'] | ['[H]\\C(=C1\\CCCN=C1C1=CN=CC=C1)C1=C(OC)C=C(OC)C=C1', '[H]\\C(=C1\\CCCN=C1C1=CN=CC=C1)C1=C(OC)C=C(OC)C=C1'] | Inclusion Criteria: - age 18-50 - meet DSM-5 criteria for Autism Spectrum Disorder, Levels 1 or 2, as defined by Autism Diagnostic Observation Schedule - non-smoking persons - in good health Exclusion Criteria: - persons with estimated verbal and nonverbal IQ < 70. - abuse of other substances. - Persons not sufficiently fluent in English to permit testing - those with history of severe head injury - Fragile X Syndrome - Rett Syndrome |
| 93 | NCT02112799 | completed | 0.7042088508605957 | phase 1 | ['chronic hepatitis b'] | ["['B18.0', 'B18.1', 'B18.2', 'B18.8', 'B18.9']"] | ['nvr 3-778', 'placebo for nvr 3-778', 'pegasys'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Healthy volunteers may be male or female between 18 and 65 years old with a BMI of 18-32kg/m2. They must be in good health not have any health condition which could interfere with the absorption, distribution or elimination of study drug, or with the clinical and laboratory assessments in this study. Patients enrolling in Part II of the study, may be male or female between 18 and 65 years of age, with a BMI of 18-35kg/m2. Patients must have HBeAg positive, chronic hepatitis B with no history of clinical decompensation, and must not have been treated for hepatitis B before. | |
| 94 | NCT02116010 | unknown status | 0.4928772449493408 | phase 1/phase 2 | ['wound infection'] | ["['O86.00', 'O86.01', 'O86.02', 'O86.09', 'O86.03']"] | ['e. coli phages cocktail', 'standard of care : silver sulfadiazine', 'p. aeruginosa, phages cocktail'] | ['CNC[C@H](O)C1=CC(O)=C(O)C=C1', 'NC1=CC=C(C=C1)S(=O)(=O)NC1=NC=CC=N1', 'CNC[C@H](O)C1=CC(O)=C(O)C=C1'] | Inclusion Criteria: - Man or woman - Adult Informed consent obtained from patient or next of kin - In-hospital patient treated for burn wounds in a burn unit - Burn wound (grafted or not) or graft harvesting area, presenting local signs of infection defined by SFETB criteria: - A local or loco-regional inflammatory reaction; - And/or an adverse and unexpected local evolution; - And/or regarding burn wounds: presence of pus, fast spontaneous debridement and separation, occurrence of blackish spots (necrosis or haemorrhage), unexplained conversion from a superficial lesion to a deep one (> 48th hour); - And/or regarding graft donor sites: presence of pus, unexplained delay in epidermisation, bedsore; - And/or regarding graft recipient sites: presence of pus, lysis of grafts, necrosis of fat located under the graft. - Burn wounds with a microbiologically documented infection, as defined by positive surface swab, due to Escherichia coli or Pseudomonas aeruginosa whatever their resistance profile - Treated by povidone-iodine Exclusion Criteria: - Pregnant or breastfeeding woman - Intercurrent condition requiring a treatment which may interfere with analysis results: such as high dose of chronic corticotherapy, immunosuppressive medication, oncologic chemotherapy - Patient included in an interventional research protocol with therapeutic intervention still ongoing upon inclusion time or having participated into anti-infective drug trials during the previous month. - Patient considered as part of a vulnerable population - Patient for whom treatment limitation or withdrawal during study period is considered - Allergy to Silver Sulfadiazine | |
| 95 | NCT02116959 | terminated | low accrual | 0.6100159883499146 | phase 1 | ['advanced intra-ocular retinoblastoma', 'retinoblastoma'] | ["['S05.30XS', 'S05.31XS', 'S05.32XS', 'S05.30XA', 'S05.30XD', 'S05.31XA', 'S05.31XD']"] | ['melphalan', 'carboplatin', 'etoposide', 'vincristine'] | ['N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O', 'N[C@@H](CCCNC(N)=N)C(O)=O', 'OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1', 'CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1'] | Inclusion Criteria: - Age greater than or equal to 3 months up to 18 years. - Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy. Local retinal therapy such as laser photocoagulation and cryotherapy will be permitted. - Unilateral or bilateral retinoblastoma (RB) patients are eligible - Patients will be registered on study based on the local exam under anesthesia (EUA) done for diagnostic purposes prior to study entry. The EUA done at study entry should be done within 14 days prior to study entry - Patients may have had enucleation of one eye, as long as the remaining eye meets the eligibility criteria - Involved eye(s) must meet the definition for International Classification of Retinoblastoma - For unilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma): 1. Group A eye that has failed local therapy 2. Group B eye that has failed local therapy 3. Group C eye that has failed local therapy 4. Group D eye 5. Group E eye that is not buphthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age - For bilateral retinoblastoma (see Appendix 1 for International Classification of Retinoblastoma): 1. Group A and Group A eyes that have failed local therapy 2. Group A and Group B eyes that have failed local therapy 3. Group A and Group C eyes 4. Group A and Group D eyes 5. Group A and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy 6. Group B and Group B eyes that have failed local therapy 7. Group B and Group C eyes 8. Group B and Group D eyes 9. Group B and Group E eyes in which the Group E eye is not planned for enucleation after first cycle of chemotherapy 10. Group C and Group C eyes 11. Group C and Group D eyes 12. Group C and Group E eyes even if early enucleation is planned for the Group E eye. 13. Group D and Group D eyes 14. Group D and Group E eyes even if early enucleation is planned for the Group E eye. 15. Group E and Group E eyes if at least one eye is not planned for enucleation. - Adequate Renal Function defined as: creatinine clearance or radioisotope Glomerular filtration rate (GFR) ³ 70 milliliter (mL)/min/1.73 m2 OR a serum creatinine based on age and gender derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the Center for Disease Control (CDC). - Adequate hematological function defined as: 1. Absolute Neutrophil Count > 1000/microliter 2. Platelet Count > 100,000/microliter - Adequate liver function defined as total bilirubin should be less than or equal to 1.5 x upper limit of normal (ULN) for age and serum glutamic-oxaloacetic transaminase (SGOT) / aspartate aminotransferase (AST) and serum glutamic-pyruvic transaminase (SGPT) / alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN) for age - Adequate coagulation system as defined as an international normalized ratio (INR) of less than 1.4 and a partial thromboplastin time (PTT) of less than 34 - Women and men of child-bearing potential must agree to use adequate contraception such as hormonal or barrier method of birth control or abstinence prior to study entry and for the duration of study participation. Should the subject or the subject's partner become pregnant or suspect pregnancy while on protocol therapy, the treating physician must be informed immediately. Exclusion Criteria: - Any evidence of extraocular retinoblastoma clinically or by magnetic resonance imaging (MRI) of brain and orbits with and without gadolinium. MRI may be done within 21 days prior to study entry. 1. Evidence of systemic metastases on bilateral bone marrow, lumbar puncture, bone scan (or Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) scan), and/or any other additional tests done at study entry. - Patients who have previously been treated with chemotherapy (with the exception of second inclusion criteria) radiation therapy, or intra-arterial therapy. - Eyes with tumors that are amenable to local therapy with laser or cryotherapy without threat to vision - Any technical factor that would prohibit use of catheterization of the ophthalmic artery (e.g., small for age infant, untreatable allergy to contrast). - Abnormal cerebral vasculature noted on MR angiography that would increase the risk of the procedure, including but not limited to an incomplete Circle of Willis. Other abnormalities that are less severe than an incomplete Circle of Willis will be reviewed by the study chair in consultation with a neuro-interventional radiologist. - Any serious ongoing condition, such as an untreated infection or organ dysfunction. - Patients receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible. - Pregnant women are excluded from this study due to potential for teratogenic or abortifacient effects of therapy. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother breastfeeding should be discontinued upon start of protocol therapy. |
| 96 | NCT02120339 | terminated | low enrollment | 0.7437440156936646 | phase 1 | ['pulmonary hypertension', 'cardiac mri <40'] | ["['I27.0', 'I27.20', 'I27.21', 'I27.24', 'I27.29', 'P29.30', 'I27.22']"] | ['carvedilol'] | ['COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2'] | Inclusion Criteria: 1. Subjects will be eligible to participate in the study if all of the following conditions exist: 2. Age > 18 years 3. WHO category 1 pulmonary arterial hypertension (Dana Point 2008) 4. WHO functional class II-III 5. RVEF by cardiac MRI < 40% 6. Mean pulmonary artery pressure > 40 mm Hg 7. Stable on PAH-specific therapy as defined by no change in PAH-specific treatment and functional class in the past 3 months. Patient can be on either mono or combination PAH-specific therapy Exclusion Criteria: - 1. Subjects will be excluded from participation in the study if any of the following conditions exist: 2. Significant persistent bradycardia (resting heart rate < 60 bpm) without a permanent pacemaker 3. Second or third degree AV block without a permanent pacemaker 4. Significant sinus tachycardia (resting heart rate > 100 bpm) 5. Use of anti-arrhythmic drugs 6. Hypotension defined as systolic blood pressure < 100 mmHg at the time of enrollment 7. Significant illness in the past 30 days requiring hospitalization 8. Acute decompensated right heart failure within past 30 days 9. Known allergy or intolerance to carvedilol or other β blockers 10. Cardiac index < 2 l/min/m2 or right atrial pressure > 15 mm Hg 11. Asthma |
| 97 | NCT02120911 | completed | 0.4379551112651825 | phase 1/phase 2 | ['esophageal carcinoma'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['pertuzumab, trastuzumab'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Histologically proven adenocarcinoma of the intrathoracic esophagus or gastro esophageal junction. - HER2-positive tumor defined as either IHC 3+ or IHC 2+, the latter in combination with ISH+, as assessed by the sponsor-designated central laboratory (pathology AMC) on a primary tumor biopsy. - Surgical resectable (T2-3, N0-1, M0), as determined by Endoscopic Ultra Sound (EUS) and CT scan of neck, thorax and abdomen. - T1N1 tumors are eligible, T1N0 tumors and in situ carcinoma are not eligible. - Tumor length longitudinal ≤ 10 cm and radial ≤ 5 cm. - If tumor extends below the gastroesophageal (GE) junction into the proximal stomach, the bulk of the tumor must involve the esophagus or GE junction. The tumor must not extend more than 2 cm into the stomach. - No invasion of the tracheobronchial tree or presence of tracheoesophageal fistula. - Age ≥ 18 and ≤ 75 years. - ECOG performance status 0 or 1. - Adequate hematological, renal and hepatic functions defined as: - neutrophiles ≥ 1.5 x 109/L - platelets ≥ 100 x 109/L - hemoglobin ≥ 5.6 mmol - total bilirubin ≤ 1.5 x upper normal limit - creatinine clearance (Cockroft) > 60 ml/min - Adequate left ventricular ejection fraction defined as an LVEF of ≥55%. - Written, voluntary informed consent. - Patients must be accessible to follow up and management in the treatment center. Exclusion Criteria: - A tumour the epicenter of which in the stomach is greater than 5 cm of the GE junction or those within 5 cm of the GE junction without extension in the oesophagus are classified as gastric cancer. - Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, or curatively treated in situ carcinoma of the cervix, or malignancy more than 5 years prior to enrollment. - Pregnancy (positive serum pregnancy test), planning to become pregnant, and lactation. - Patient (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment. - Previous chemotherapy, radiotherapy, treatment with an anti-HER2 antibody or with small molecule HER2 inhibitors. - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before randomization. - Pulmonary fibrosis and/or severely impaired lung function. - Pre-existing motor or sensory neurotoxicity greater than WHO grade 1. - Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment, including prior allergic reactions to drugs containing Cremophor, such as teniposide or cyclosporine. - Dementia or altered mental status that would prohibit the understanding and giving of informed consent - Inadequate caloric- and/or fluid intake. | |
| 98 | NCT02121483 | completed | 0.929180383682251 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['empagliflozin medium dose', 'empagliflozin high dose', 'empagliflozin low dose'] | ['CN(C)C(=N)NC(N)=N', '[H][C@@]1(CCOC1)OC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@]2([H])O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]2([H])O)C=C1', '[H][C@@]1(CCOC1)OC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@]2([H])O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]2([H])O)C=C1'] | Inclusion criteria: - Children and adolescents with type 2 diabetes mellitus - Insufficient glycaemic control (HbA1c <=10.5%) despite diet and exercise and/or metformin and/or stable basal or MDI insulin - Negative for Islet Cell Antigen and Glutamic Acid Decarboxylase autoantibodies and fasting C-peptide levels >= 0.85 ng/ml - BMI > 50th percentile for age and sex Exclusion criteria: - Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l) - History of acute metabolic decompensation such as diabetic ketoacidosis within 3 months before the screening visit with the exception of acute de-compensation at the time of type 2 diabetes diagnosis - Treatment with weight reduction medications within 4 weeks before randomisation | |
| 99 | NCT02121756 | completed | 0.6262799501419067 | phase 1/phase 2 | ['hiv infection'] | ["['Z21']"] | ['dipyridamole', 'placebo, then dipyridamole'] | ['OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1', 'OCCN(CCO)C1=NC2=C(N=C(N=C2N2CCCCC2)N(CCO)CCO)C(=N1)N1CCCCC1'] | Inclusion Criteria: - HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. - On ART for at least 12 months prior to study entry with a regimen that includes three or more antiretroviral medications. More information on this criterion is available in the protocol. - Plasma HIV-1 RNA <50 copies/mL by any standard clinical assay at screening and for a minimum of 12 months prior to entry, confirmed by at least 2 measurements prior to study entry, one of which must be at least 48 weeks prior to study entry and one of which must be 61 days and 48 weeks prior to study entry. All plasma HIV-1 RNA measurements in the 12 months prior to study entry must be <50 copies/mL (with the exception that a single detectable measurement of ≤ 200 copies/mL is permitted if the RNA levels immediately before and after are <50 copies/mL). - Stable ART regimen for at least 8 weeks prior to study entry and no plans to change ART regimen for at least 6 months following study entry. - Ability and willingness to provide informed consent. - In the opinion of the investigator, no medical, mental health or other condition that precludes participation. - Laboratory values obtained within 60 days prior to entry. - Hemoglobin ≥10.0 g/dL - Platelet count ≥100,000/mm3 - INR ≤ 1.5 (for rectal tissue subset only) - PTT <2x ULN (for rectal tissue subset only) - AST and ALT < 2.5 x upper limit of normal (ULN) - Total bilirubin < 2.5 x ULN (except if hyperbilirubinemia is secondary to atazanavir). - Creatinine ≤ 1.5 x ULN - Hepatitis B surface antigen negative - Hepatitis C antibody negative (note: subject with HCV Ab positive is eligible if Hepatitis C RNA PCR (viral load) is undetectable) - For females of reproductive potential, negative serum or urine pregnancy test at screening and within 72 hours prior to study entry. Females of reproductive potential include women who have not been post-menopausal for at least 24 consecutive months, (i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy and/or bilateral oophorectomy). - Females of reproductive potential who are participating in sexual activity that could lead to pregnancy must agree to use one method of acceptable contraception while receiving protocol-specified treatment and for 4 weeks after stopping the treatment. These methods include condoms (male or female) with or without a spermicidal agent; diaphragm or cervical cap with spermicide; intrauterine device (IUD); and hormone-based contraceptive. - Females not of reproductive potential (girls who have not reached menarche, women who have been post-menopausal for at least 24 consecutive months, or women who have undergone surgical sterilization, e.g., hysterectomy, bilateral oophorectomy, or bilateral tubal ligation or salpingectomy) are eligible without requiring the use of a contraceptive. Self- report is acceptable documentation of sterilization, other contraceptive methods, and menopause. - Rectal Tissue Subset only: Willing to abstain from receptive anal intercourse and practices involving insertion of anything in the rectum (drug, enema, penis, or sex toy) for 72 hours prior to rectal biopsy and for 7 days post-biopsy to minimize risk of bleeding complications. Exclusion Criteria: - Pregnancy or breast-feeding. - Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation. - Known cardiovascular disease (history of MI, coronary artery bypass graft surgery, percutaneous coronary intervention, stroke, transient ischemic attack, peripheral arterial disease with ABI <0.9 or claudication). - Uncontrolled type II diabetes mellitus. - Known chronic inflammatory conditions such as, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune hepatitis, myositis, or myopathy. - History of asthma requiring medical treatment within 2 years prior to study entry with the exception of the use of albuterol inhaler for mild intermittent asthma. - Serious illness requiring systemic treatment and/or hospitalization within 14 days prior to entry. - Use of any of the following medications for more than 3 consecutive days within the 60 days prior to study entry: - Immunosuppressives (e.g., azathioprine, corticosteroids [physiologic replacement doses are allowed], cyclosporine, mycophenolate, NSAIDs (nonsteroidal anti-inflammatory drugs), sirolimus, sulfasalazine, tacrolimus) - Immune modulators (e.g., cytokines [e.g., IL-2], granulocyte colony stimulating factor, growth hormone, tumor necrosis factor antagonists, thalidomide) - Antineoplastic agents - Anticoagulants (e.g., warfarin and heparin) - Anti-platelet drugs (e.g., clopidogrel and aspirin) - Vaccinations within 1 week prior to the pre-entry or study entry visits. Routine standard of care vaccinations including hepatitis A and/or B, influenza, pneumococcal, and tetanus are permitted if administered at least 7 days before pre-entry and entry evaluations. - Participation on any HIV immunotherapy or therapeutic vaccination trials within 6 months prior to study entry. - Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. - Use of investigational therapies within 30 days prior to study entry. - Rectal Tissue Subset only: - Abnormalities of the colorectal mucosa or significant colorectal symptom(s), which in the opinion of the study investigator represent a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids. - NOTE: Abnormalities of the colorectal mucosa will be assessed at the time of the enrollment flexible sigmoidoscopy. If no significant colorectal abnormalities or symptoms are present then the participant will undergo the enrollment procedures. If abnormalities are present then no biopsies will be performed and the participant will not be enrolled into the rectal tissue subset but will continue participation in the main study. - Active untreated gonorrhea, or chlamydia infection within 30 days prior to study entry (subjects diagnosed with rectal gonorrhea or chlamydia infection at screening may be treated during the screening period provided the treatment is at least 30 days prior to entry). - Exclusions for spirometry testing (for participants enrolled under Version 2.0) Participants will not undergo pre- and post-bronchodilator spirometry if they have any of the following: - Abdominal or cataract surgery within 3 months. - Myocardial infarction or stroke within the past 3 months. - Acute onset of shortness of breath, cough, fever or heart condition such as tachycardia, angina or arrhythmias with 4 weeks prior to enrollment. - Increasing respiratory symptoms or febrile (temperature >100.4°F [38°C]) within 4 weeks of study entry. - Uncontrolled hypertension defined as systolic > 160 mm Hg or diastolic > 100 mm Hg from an average of two or more readings. Participant with controlled hypertension may undergo spirometry. - Prior history of adverse reaction to albuterol. | |
| 100 | NCT02121860 | completed | 0.5213466882705688 | phase 1 | ['hepatic impairment', 'liver diseases', 'digestive system diseases'] | ["['Z73.82', 'G31.84', 'M10.38', 'M10.30', 'M10.311', 'M10.312', 'M10.319']", "['K76.9', 'K71.8', 'K70.9', 'K71.9', 'K75.9', 'P78.84', 'Q44.6']", "['K92.9', 'B57.30', 'B57.39', 'K92.89', 'O99.611', 'O99.612', 'O99.613']"] | ['idn-6556'] | ['C[C@H](NC(=O)C(=O)NC1=CC=CC=C1C(C)(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)COC1=C(F)C(F)=CC(F)=C1F'] | Inclusion Criteria: All Subjects: - Male or female subjects 18 years of age or older, able to provide written informed consent, understand and comply with all scheduled visits, and other requirements of the study - Body mass index (BMI) 18.0 - 40.0 kg/m2 and body weight >45 kg - Willingness to utilize two reliable forms of contraception (for both males and females of childbearing potential) from Screening to one month after the last dose of study drug Matched Healthy Volunteers: - Medically healthy as determined by the Investigator - Supine blood pressure ≤145/90 mmHg - No significant uncontrolled systemic or major illness that, in the opinion of the Investigator, would preclude the subject from participating in and completing the study - Demographically comparable to subjects with hepatic impairment as follows: 1. Mean body weight within ±15 kg 2. Mean age within ±10 years 3. Similar gender ratio Subjects with Hepatic Impairment: - Evidence of hepatic disease 1. Score ≥ 2 on one of the Child-Pugh parameters, or 2. Histological or imaging diagnosis of cirrhosis, or 3. Presence of esophageal varices, or 4. Abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) levels - Meet one of the following criteria for Child-Pugh classification for hepatic impairment during Screening 1. Mild hepatic impairment: Class A (Child-Pugh Scores 5-6 points) 2. Moderate hepatic impairment: Class B (Child-Pugh Scores 7-9 points) 3. Severe hepatic impairment: Class C (Child Pugh Scores 10-15 points) - Supine blood pressure ≤160/100 mmHg Exclusion Criteria: All Subjects: - Known infection with human immunodeficiency virus (HIV) upon serological testing - Evidence of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) - Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the pharmacokinetics of the investigational medicinal product (e.g., inflammatory bowel disease, resections of the small or large intestine, etc.) - History of febrile illness within 5 days prior to dosing Note: Subjects can be rescreened once afebrile and more than 5 days have elapsed since the febrile illness. - Known ongoing drug abuse within one month prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during Screening and/or at Day -1 - Subjects with active or history of malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) - Dosing in another clinical trial within 30 days prior to the study drug administration - If female: known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding Matched Healthy Volunteers: - Evidence of clinically significant liver disease or liver damage (e.g., hepatitis B or C, autoimmune hepatitis, primary biliary cirrhosis, non-alcoholic fatty liver disease, elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) that is considered clinically significant by the Investigator, etc.) - Screening creatinine clearance <80 mL/min using the Cockcroft-Gault equation - History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of >450 milliseconds (msec) - History of regular alcohol consumption exceeding 28 drinks/week (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of spirits) within 6 months of Screening Subjects with Hepatic Impairment: - Fluctuating or rapidly deteriorating hepatic function, as indicated by strongly varying or worsening of clinical and/or laboratory signs of hepatic impairment during Screening period and up to Day -1 (e.g., advanced ascites, infection of ascites, fever, active gastrointestinal bleeding) - History of liver transplant, or have a transjugular intrahepatic portosystemic shunt, and/or have undergone portacaval shunting - History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QT or QTc interval of >480 milliseconds (msec) - Screening creatinine clearance <50 mL/min using the Cockcroft-Gault equation |