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| # | nctid | status | why_stop | prediction | phase | diseases | icdcodes | drugs | smiless | criteria |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | NCT01132482 | completed | 0.6471551060676575 | phase 2 | ['cystic fibrosis'] | ["['E84.9', 'Z14.1', 'E84.0', 'E84.11', 'E84.8', 'E84.19', 'P09.4']"] | ['sildenafil', 'placebo'] | ['CCCC1=NN(C)C2=C1NC(=NC2=O)C1=C(OCC)C=CC(=C1)S(=O)(=O)N1CCN(C)CC1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and genotype with two F508del CFTR mutations, and accompanied by one or more clinical features consistent with the CF phenotype 2. Male or female subjects ≥ 18 years of age 3. FEV1 ≥ 50% predicted (Hankinson) 4. Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit 5. Ability to reproducibly perform spirometry (according to ATS criteria) 6. Ability to understand and sign a written informed consent or assent and comply with the requirements of the study 7. Willing and able to perform nasal potential difference testing 8. No changes in use of nasal medications within 2 weeks of screening visit 9. If on Orkambi, has been on stable Orkambi dose for at least 4 weeks at day 1. Exclusion Criteria: 1. History of hypersensitivity to sildenafil 2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0) 3. Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study 4. History of significant hepatic (SGOT or SGPT > 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure >55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine >1.8 mg/dL.) 5. Inability to swallow pills 6. Previous lung transplantation 7. Use of concomitant nitrates, α-blocker, or Ca channel blocker 8. Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin, verapamil) 9. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data 10. Weight less than 40 kg 11. History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening 12. History of nasal disease or nasal surgery that would, in the opinion of the investigator, impede accurate measurements of NPD 13. Use of anticoagulant medication (e.g. heparin, coumadin) 14. Resting room air oxygen saturation <93% 15. Use of nighttime oxygen 15) History of migraine headaches 16) Baseline BP of < 90/50 mm Hg | |
| 2 | NCT01288573 | completed | 0.39079782366752625 | 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 | |
| 3 | NCT01450826 | completed | 0.41988399624824524 | phase 2 | ['nausea', 'vomiting', 'glioma'] | ["['R11.0', 'R11.11', 'R11.2']", "['R11.10', 'R11.12', 'R11.14', 'R11.11', 'K91.0', 'O21.2', 'O21.8']"] | ['aprepitant', 'ondansetron'] | ['[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', 'CN1C2=C(C3=CC=CC=C13)C(=O)C(CN1C=CN=C1C)CC2'] | Inclusion Criteria: - Patients must have histologically confirmed diagnosis of glioma (either low or high grade) and be either chemotherapy naïve or non-naïve and scheduled to receive temozolomide-based +/- Bevacizumab- based chemotherapy. Patients with recurrent disease whose diagnostic pathology confirmed glioma (either low or high grade) will not need re-biopsy. - Age ≥ 18 years - ≤ 2 prior chemotherapeutic regimens - Patient is scheduled to receive temozolomide at either 150 mg/m2 or 200mg/m2 by mouth for 5 days out of a 28 day cycle +/- bevacizumab. - Study participation will occur during the first cycle of the 5 day temozolomide course. - An interval of at least 6 weeks between prior surgical resection and study enrollment - Karnofsky ≥ 60%. - Hematocrit > 29%, absolute neutrophil count (ANC) > 1,000 cells/µl, platelets > 100,000 cells/µl - Serum creatinine < 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal - For patients on oral corticosteroids, they must be stable clinically on corticosteroids or tapered off prior to starting the study drug. For patients taking dexamethasone, the dose should not exceed 8 mg qd (or 4 mg twice a day), if clinically stable, and the dose should not be escalated over entry dose level, if clinically possible. The patient's dose of dexamethasone will be evaluated by the PI, the patient's study physician, and/or the study pharmacist on a case by case basis for safety. All doses of oral corticosteroids will be reduced by 50% to avoid drug to drug interactions with Aprepitant, unless oral corticosteroids are at physiologic dose (e.g. dexamethasone 1 mg, prednisone 10 mg, or cortisone 30 mg). It is recommended that oral corticosteroid doses be escalated back to full dose on Day 7 (2 days after Aprepitant is discontinued) based on Aprepitant half-life pharmacokinetic data, and expert clinical opinion. - Signed informed consent approved by the Institutional Review Board prior to patient entry - If sexually active, patients will take contraceptive measures for the duration of protocol treatment and continue until one month after treatment. The efficacy of hormonal contraceptives during and for 28 days following the last dose of Aprepitant may be reduced. Alternative or back-up methods of contraception must be used. - Approved rescue medication for the treatment of nausea and vomiting is permitted at the discretion of the investigator. The rescue antiemetics allowed will include: ondansetron, granisetron and lorazepam. Exclusion Criteria: - Pregnant or breast-feeding (While both aprepitant and ondansetron are classified as Category B drugs, an eligibility criteria for this study is that the patient be scheduled to receive a temozolomide-based chemotherapy regimen +/- bevacizumab, which are Category D and C drugs respectively. Therefore, while not considered necessary for the administration of the current study drugs, a pregnancy test should be a part of normal clinical care for the patients in this study, if the patient is determined to be of child-bearing potential.) - No prior nitrosourea (e.g. lomustine, carmustine) - Inability or unwillingness to understand or cooperate with study procedures - Concurrent administration of CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs) including phenytoin, phenobarbitol, carbamazepine, oxcarbazepine or primidone - Prohibited medications: Patients taking CYP3A4 enzyme inducers and moderate or strong inhibitors will be excluded from this trial. - Received any drug with potential anti-emetic effect within 24 hours prior to the start of study-designated chemotherapeutic agent: HT3 receptor or substance P/neurokinin 1(NK1) receptor antagonists; Dopamine receptor antagonists (metoclopramide); Phenothiazine anti-emetics (prochlorperazine, thiethylperazine and perphenazine); Diphenhydramine, scopolamine, chlorpheniramine maleate, trimethobenzamide; Haloperidol, droperidol, tetrahydrocannabinol, or nabilone - Any vomiting, retching or NCI Common Toxicity Criteria v.4.0 grade 2-4 nausea 24 hours preceding chemotherapy - Ongoing vomiting from any organic etiology - Will receive radiotherapy of cranium within one week prior to or during the study | |
| 4 | NCT01562197 | completed | 0.3334716856479645 | phase 2 | ['glioblastoma multiforme'] | ["['L51.0', 'L51.8', 'L51.9']"] | ['axitinib', 'axitinib plus lomustine'] | ['[H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H]', 'ClCCN(N=O)C(=O)NC1CCCCC1'] | 1. Histopathological diagnosis of glioblastoma (= WHO grade IV glioma of the central nervous system); both "de novo" and "secondary" glioblastoma are eligible; 2. Diagnosis of glioma recurrence or progression following prior treatment with surgery, radiation therapy and alkylating chemotherapy (defined as significant [according to the investigators individual assessment] growth or recurrence of the glioblastoma demonstrated on sequential Gd-MRI before the time of recruitment). 3. The following disease characteristics should be present: 1. Presence of a measurable tumor lesion that is characterized by gadolinium enhancement on T1-MRI of the brain (with a longest diameter of > 10 mm); 2. Enhancing characteristics of the glioblastoma as compared to the normal brain on 18F-FET PET (patients with a non-enhancing lesion are not eligible); 3. No evidence of clinically meaningful spontaneous intra-tumoral hemorrhage on baseline MRI-imaging or in the prior disease history; 4. No contraindication for evaluation by Gd-MRI or 18F-FET PET of the brain; 5. Archival glioma tissue must be available for collection and storage in a centralized tumor bank; 6. An interval of at least 3 months (12 weeks) after the end of prior radiation therapy; and an interval of at least 4 weeks after the last administration of cytotoxic drug treatment (6 weeks in case of administration of a nitrosureum or mitomycin C); and an interval of at least 4 weeks after the last administration of any other kind of anti glioblastoma treatment; 7. A stable dose of corticosteroids for at least 14 days before the initiation of study treatment with axitinib; 8. WHO performance status of 0 or 1; 9. Life expectancy of ≥12 weeks; 10. Male or female, 18 years of age or older; 11. Resolution of all acute toxic effects of prior systemic therapy, radiotherapy or surgical procedure to NCI CTCAEv3.0 grade 0 or 1 or back to baseline except for alopecia or hypothyroidism; 12. Adequate organ function as defined by the following criteria: - Total serum bilirubin < 1.5 x ULN (patients with Gilbert's disease exempt) - AST and ALT < 2.5 x upper limit of normal (ULN); - Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥60 mL/min - Absolute neutrophil count (ANC) > 1500/mm³ without growth factor support - Platelets > 75 000 cells/mm³ - Hemoglobin ≥9 g/dL (which may be obtained by transfusion or growth factor support) - Urinary protein <1+ by urine dipstick. If dipstick is ≥1+ then a 24-hour urine collection should be done and the patient may enter only if urinary protein is <2 grams per 24 hours 13. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.; 14. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception measures during the period of therapy which should be continued for 4 weeks after the last dose of axitinib. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate; 15. No previous treatment on an axitinib trial; 16. No previous treatment with a VEGF or VEGFR-targeted drug (including, but not limited to bevacizumab, aflibercept, cediranib, sorafenib, sunitinib, XL184, and pazopanib); 17. No gastrointestinal abnormalities including: 1. Inability to take oral medication. 2. Requirement for intravenous alimentation. 3. Prior surgical procedures affecting absorption including gastric resection. 4. Treatment for active peptic ulcer disease in the past 6 months. 5. Malabsorption syndromes. 6. Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; 18. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be ≤140 mm Hg, and the baseline diastolic blood pressure readings must be ≤90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible; 19. No concurrent treatment: 1. In another therapeutic clinical trial; 2. With a drug having pro-arrhythmic potential; 3. With enzyme inducing anti-epileptic drugs (EIAED) within 14 days before dosing with axitinib (e.g. carbamazepine, phenobarbital, phenytoin); 20. No current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine). 21. No current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort). 22. No requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed. 23. No active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 24. No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure or any unstable arrhythmia, cerebrovascular accident or transient ischemic attack, within the 12 months prior to study drug administration. No current or recent (within 1 month) use of a thrombolytic agent or a thrombo-embolic event; 25. No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness; 26. No serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment; 27. No history of a malignancy (other than glioma) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years; 28. No major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of treatment. (Also excluded are patient with fine needle aspirations within 7 days of treatment); 29. No pregnancy or breastfeeding; 30. No history of hemoptysis > ½ tsp of bright red blood per day within past 1 week; 31. No other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study; 32. No dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol; 33. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrollment; 34. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests and other study procedures. | |
| 5 | NCT01610869 | completed | 0.3160616457462311 | phase 2 | ['ovarian cancer', 'fallopian tube cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C57.00', 'C57.01', 'C57.02']"] | ['bibf 1120'] | ['COC(=O)C1=CC=C2C(NC(=O)\\C2=C(/NC2=CC=C(C=C2)N(C)C(=O)CN2CCN(C)CC2)C2=CC=CC=C2)=C1'] | Inclusion Criteria: - Female subjects, ≥18 years, histologically proven recurrent advanced epithelial ovarian, fallopian tube or primary peritoneal carcinomas - Have either undergone a hysterectomy or bilateral oophorectomy/salpingectomy and/or have been postmenopausal for 24 consecutive months (i.e. who have not had menses at any time in the preceding 24 consecutive months without an alternative medical cause) - Performance status 0-2 - Adequate organ function - Life expectancy >6 weeks - Has received 2 or more lines of chemotherapy for ovarian cancer and patient is platinum resistant or platinum intolerant or not suitable for any further standard intravenous chemotherapy - No previous oral cyclophosphamide, nintedanib, or other tyrosine kinase inhibitors such as cediranib but patients can have received anti-VEGF therapies such as bevacizumab as they will be stratified for this - Measurable lesions according to RECIST 1.1 criteria or serum CA125 levels for evaluation by GCIG CA125 criteria are welcomed but not a prerequisite for inclusion as response will only be assessed for those with evaluable disease - Able to give written informed consent and to complete QoL Exclusion Criteria - Carcinosarcoma or malignant tumour of non-epithelial origin (e.g. germ cell tumour, sex cord-stromal tumour) of the ovary, fallopian tube or peritoneum - Clinically relevant non-healing wound, ulcer (intestinal tract, skin) or bone fracture - Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other GI disorders or abnormalities that would interfere with drug absorption or inability to take oral medication - Active brain metastases (i.e. symptoms deteriorating, changing condition in < 4 weeks) or leptomeningeal disease. Trial entry is allowed if the brain metastases are stable (asymptomatic or condition stable for > 4 weeks). - Dexamethasone for brain metastases is allowed if administered as stable dose for > 4 weeks before randomisation (if < 4 weeks then the patient is not eligible) - Clinically relevant therapy-related toxicity from previous chemotherapy and radiotherapy - History of major thromboembolic event within the last 6 months, such as pulmonary embolism or proximal deep vein thrombosis, unless on stable therapeutic anticoagulation (>3 months if on warfarin, PT / INR needs to be monitored regularly as per table 8.1 in protocol) - Known inherited or acquired bleeding disorder - Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within the past 6 months, congestive heart failure > NYHA II, severe peripheral vascular disease, significantly relevant pericardial effusion - History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months - Radiographic evidence of cavitating or necrotic tumours with invasion of adjacent major blood vessels - Laboratory values indicating an increased risk for adverse events: 1. calculated GFR < 45 ml/min. Sites can use any calculation method according to local practice. 2. absolute neutrophil count (ANC) < 1.5x109/L 3. platelets < 100 x109/L 4. haemoglobin < 90 g/L 5. proteinuria CTCAE 2 or greater 6. total bilirubin > x 2 ULN 7. ALT and/or AST > 1.5 x ULN 8. unless liver metastases present when ALT or AST > 2.5 ULN 9. International normalized ratio (INR) > 2 or activated partial thromboplastin time (APTT) >1.5 x ULN in the absence of therapeutic anticoagulation. INR > 4 or APTT > 2.5 x ULN in presence of therapeutic anticoagulation - Serious infections in particular if requiring systemic antibiotic (antimicrobial, antifungal or antiviral therapy), including hepatitis B and/or C infection, HIV- infection - Poorly controlled diabetes mellitus or patient on sulphonylurea-type hypoglycaemics (e.g. gliclazide) as main diabetic control (as contraindicated with cyclophosphamide) - Previous breast cancer patients are permitted only if diagnosis and any chemotherapy treatment for this was > 5 years previously and there is no evidence of metastatic breast cancer at trial entry (Please contact UCL CTC / CI if patient still on hormone treatment for breast cancer). - Other malignancy diagnosed within the past 5 years. In exception to this rule, the following malignancies may be included: 1. non-melanoma skin cancer (if adequately treated) 2. cervical carcinoma in situ (if adequately treated) 3. prior or synchronous endometrial cancer (if adequately treated), provided all of the following criteria are met: G1 or G2, no LVSI and FIGO (2010) stage IA only - Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease or a laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study - Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule e.g. active alcohol or drug abuse - Any contraindications for therapy with cyclophosphamide, e.g. a history of severe hypersensitivity reactions to listed excipients for cyclophosphamide treatment with other investigational drugs - Patients should not commence trial treatment within 6 weeks of any major surgical procedure - Participation in another clinical trial testing a drug within the past four weeks before start of therapy or concomitantly with this trial - Chemotherapy, including immunotherapy or monoclonal antibody treatment (VEGF) within 4 weeks of starting study treatment - Hormone treatment for ovarian cancer within 2 weeks of starting study treatment (ongoing HRT is allowable) - Any previous tyrosine kinase inhibitor treatment that has predominantly anti-angiogenic action - Radiotherapy within 3 months not allowed except when given for symptom control >28d previously. All patients receiving any radiotherapy will require evidence of recurrent ovarian cancer outside the irradiated field either on imaging or via rising CA125 - Hypersensitivity to nintedanib, peanut or soya, or to any of the excipients of nintedanib | |
| 6 | NCT01641107 | active, not recruiting | 0.716072678565979 | phase 2 | ['philadelphia positive', 'bcr-abl positive', 'acute lymphoblastic leukemia'] | ["['C91.01', 'C91.02', 'C91.00']"] | ['ponatinib'] | ['CN1CCN(CC2=CC=C(NC(=O)C3=CC(C#CC4=CN=C5C=CC=NN45)=C(C)C=C3)C=C2C(F)(F)F)CC1'] | Inclusion Criteria: 1. To be classified as having Ph+ ALL, patients must have >20% blasts in bone marrow at the time of diagnosis and no prior history of CML. 2. Patients with previously untreated Ph+ and/or BCR/ABL + ALL: - age ≥ 60 years old or - age ≥ 18 years old, but unfit for program of intensive therapy and allogeneic SCT 3. Adequate hepatic function as defined by the following criteria: - total serum bilirubin ≤1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome - alanine aminotransferase (ALT) ≤2.5 × ULN - aspartate aminotransferase (AST) ≤2.5 × ULN. 4. Adequate pancreatic function as defined by the following criterion: - serum lipase and amylase ≤1.5 × ULN. 5. For females of childbearing potential, a negative pregnancy test must be documented prior to randomization. 6. Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from randomization through 4 months after the end of treatment. 7. Signed written informed consent according to ICH/EU/GCP and national local laws. Exclusion Criteria: 1. WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG). 2. Active HBV or HCV hepatitis, or AST/ALT ≥ 2.5 x ULN and bilirubin ≥ 1.5 x ULN. 3. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis. 4. History of alcohol abuse. 5. Ongoing or active infections. 6. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL). 7. Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: - any history of myocardial infarction, stroke, or revascularization - unstable angina or transient ischemic attack within 6 months prior to enrollment - congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment - history of clinically significant (as determined by the treating physician) atrial arrhythmia - any history of ventricular arrhythmia - any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism . 8. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control. 9. Taking medications that are known to be associated with Torsades de Pointes. 10. Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib. 11. Creatinine level > 2.5mg/dl or Glomerular Filtration Rate (GFR) < 20 ml/min or proteinuria > 3.5 g/day. 12. Impairment of gastrointestinal (GI) function, or a GI disease that may significantly alter the absorption of study drugs (e.g. rare hereditary problems of galactose intolerance , the Lapp lactase deficiency or glucose-galactose malabsorption, severe malabsorption syndrome, or extended small bowel resection). 13. Patients who are currently receiving treatment with any of the medications listed in Appendix E if the medications cannot be either discontinued or switched to a different medication prior to starting study drug. The medications listed in Appendix E have the potential to prolong QT. 14. Patients who have received any investigational drug ≤ 4 weeks. 15. Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy. 16. Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of Ponatinib). Post menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 4 months following discontinuation of study drugs. 17. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention. 18. Patients unwilling or unable to comply with the protocol. | |
| 7 | NCT01717053 | active, not recruiting | 0.49648237228393555 | phase 2 | ['prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['abiraterone acetate', 'androgen deprivation', 'prednisone'] | ['[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C', '[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C'] | Inclusion Criteria: - One of the following high risk criteria: - Gleason Score 7 with PSA ≤ 20 ng/ml and clinical T1-2, or - Gleason Score 8-10, PSA ≤ 20 ng/ml and clinical T1-2a, or - PSA 10.1-40 ng/ml with GS < 7 and clinical T1-2, or - Clinical T3 with Gleason Score < 7 and PSA ≤ 10 ng/ml. - ECOG Performance Status ≤ 1 - Digital rectal exam within 90 days of registration on study - CBC with differential with adequate bone marrow function defined as follows: - Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3, Platelets > 100,000/µL and Hemoglobin ≥ 9g/dL - Serum potassium ≥ 3.5 mEq/L - Serum albumin > 3.0 g/dl - Total bilirubin < 1.5 X of institutional upper limit of normal (ULN) - AST(SGOT)/ALT(SGPT) < 1.5 X ULN - Calculated creatinine clearance > 60 mL/min - Age > 18 years - Able to swallow a whole tablet and take abiraterone acetate on an empty stomach (defined as no food for two hours before and one hour after abiraterone acetate ingestion) - Ability to understand and sign a written informed consent document - Written authorization for use and release of health and research study information has been obtained - Be willing/able to adhere to the prohibitions and restrictions specified in this protocol - Subjects who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protections as determined acceptable by the principal investigator during the study and for 1 week after the last dose of abiraterone acetate. Exclusion Criteria: - Bone, visceral or soft tissue metastasis, including lymph nodes (>2 cm in longest diameter) - Prior therapy for prostate cancer [Exceptions: LHRH agonist or antagonist may have been initiated within 30 days prior to enrollment. Bicalutamide may have been given within 60 days of enrollment as long as it has been stopped at least 7 days before enrollment and total duration was no longer than 30 days. This is to allow enrollment of those who have been given bicalutamide as a bridge for LHRH agonist/antagonist. It is highly unlikely a short non-overlapping course of bicalutamide will interact with abiraterone acetate in a measurable way. Previous alpha-reductase inhibitor use allowed IF patient has not been taking for at least 30 days prior to abiraterone acetate initiation, OR if alpha reductase inhibitor was not used as a primary treatment of prostate cancer and the PSA on alpha-reductase inhibitor remains within eligibility when doubled. ] - Known serum testosterone ≤ 150 ng/dl or symptoms of hypogonadism (fatigue, hot flashes, hair loss, loss of muscle mass, osteoporosis, low libido, depression) prior to ADT initiation not explained by other medical co-morbidity OR history of testosterone supplement. If questionable, serum testosterone level greater than 150 ng/dl can be used to exclude hypogonadism. - Previous malignancy within 3 years other than non-melanomatous skin cancer and non-muscle invasive bladder cancer - Previous pelvic radiotherapy that would prevent prostate/SV irradiation - Uncontrolled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy - History of gastrointestinal disorders that may interfere with the absorption of study drug (including gastric bypass surgery) - Concurrent spironolactone use - Significant concurrent medical condition that would make prednisone/prednisolone use contraindicated or would interfere with the patient's ability to participate in the trial - Receiving any investigational agents currently or within 30 days prior to study screening - Prior demonstrated hypersensitivity, intolerance or allergy to abiraterone acetate, prednisone or their excipients - Active co-morbidity, defined as follows: - Chronic liver disease with cirrhosis (Child-Pugh B or C) or active hepatitis B or C - History of pituitary or adrenal dysfunction - Poorly controlled diabetes mellitus (A1c >9% or history of complications including peripheral neuropathy, end organ damage, hospitalization, amputation) - Poorly controlled glaucoma - Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III-IV heart disease or known cardiac ejection fraction measurement of < 50% at baseline. - Clinical evidence of active infection of any type, including active or symptomatic viral hepatitis. - Known immune deficiency and/or HIV-positive patients - Any medical condition that warrants long-term corticosteroid use in excess of study dose - Patients taking strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) - Any condition that in the opinion of the Principal Investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing the study requirements | |
| 8 | NCT01757327 | withdrawn | poor accrual | 0.3933865427970886 | phase 2 | ['breast neoplasms'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['erismodegib', 'placebo'] | ['[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', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Pre-Registration Inclusion Criteria - Diagnosis of pathologic stage II or III ER, PR, and HER2 negative primary invasive ductal or invasive lobular breast carcinoma. ER negative is defined as an Allred score of 0-2. PR negative is defined as an Allred score of 0-4. HER2 negative is defined as an IHC score of 0-1 and/or not-amplified by FISH testing. - All surgery for breast cancer (as defined by surgical excision of the cancer with a negative margin or mastectomy) must be complete. - Undergone axillary lymph node surgery (either sentinel lymph node biopsy or axillary lymph node dissection) per institutional standard. - Completed all (neo) adjuvant chemotherapy and radiation therapy as recommended by the treating physicians. - Completed the most recent cancer therapy (surgery, radiation, or chemotherapy) no less than 3 and no more than 24 weeks prior to registration. Note: patients who received experimental neoadjuvant or adjuvant therapy or surgical therapy (with the exception of Hh inhibitors) through participation in clinical trial are NOT excluded from this study as long as the other trial does not exclude patients from enrolling into an additional adjuvant clinical trial and enrolling into this trial will not compromise the endpoints (primary and secondary) of the primary clinical trial. In addition, patients must have completed the experimental therapy no less than 4 weeks or 5 half lives (whichever is longer) and no more than 24 weeks prior to registration. For those patients who have enrolled into a neoadjuvant / adjuvant / surgical trial, all endpoints of these trials will be reviewed prior to consenting the patient for the sonidegib trial. - At least 18 years of age. - ECOG performance status ≤ 1 - Patient (or legally authorized representative if applicable) must be able to understand and willing to sign an IRB approved written informed consent document. Pre-Registration Exclusion Criteria - Concurrent treatment with any other standard therapy (e.g. chemotherapy, targeted therapy or radiotherapy) or within 3 weeks of starting sonidegib. - Treatment with investigational anti-cancer agent within 4 weeks or 5 half-lives whichever is longer, of initializing treatments with sonidegib. - Previous treatment with systemic sonidegib or with other Hh pathway inhibitors. - Diagnosis of a neuromuscular disorder (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) or 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 sonidegib treatment. If it is essential that the patient stays on a statin to control hyperlipidemia, only pravastatin may be used with extra caution. - Known to be HIV-positive on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with sonidegib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated. Registration Inclusion Criteria - Presence of bone marrow DTCs after the completion of all intended breast cancer therapy including surgery, (neo) adjuvant chemotherapy therapy, and radiation as indicated. Note: Bone marrow aspiration will be performed in consented patients to evaluate DTCs provided patients meet all eligibility criteria as described in this section. - ECOG performance status ≤ 1 - Normal bone marrow and organ function as defined below: - Leukocytes ≥ 3,000/mcL - Absolute neutrophil count ≥ 1,500/mcL - Hemoglobin ≥ 9.0 g/dL - Platelets ≥ 80,000/mcL - Total bilirubin ≤ 1.5 x IULN - AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN - Plasma creatine phosphokinase (CK) < 1.5 x ULN - Creatinine ≤ 1.5 x ULN OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal - Able to swallow capsules. - Women of childbearing potential must have a negative serum pregnancy test ≤ 7 days from date of registration. Women of childbearing potential must agree to use dual forms of adequate contraception (barrier method of birth control, non-hormonal IUD or IUS, abstinence) prior to study entry duration of study participation and 20 months after final dose of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Registration Exclusion Criteria - Evidence of distant metastasis present by CT scan, bone scan, or physical exam within one year prior to entry into the trial. - History of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to sonidegib or other agents used in the study. - Planning to embark on a new strenuous exercise regimen after initiation of study treatment. Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on sonidegib treatment. - Diagnosis of a medical condition that would lead to lack of physical integrity of the upper gastrointestinal tract or known malabsorption syndrome. - Taking warfarin and Coumadin derivatives because of potential interactions with sonidegib. - Receiving treatment with medications known to be moderate or strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic indices and that cannot be discontinued before starting treatment with sonidegib. Medications that are strong CYP3A4/5 inhibitors should be discontinued at least 7 days and strong CYP3A4/5 inducers at least 2 weeks prior to starting treatment with sonidegib. - Concurrent uncontrolled medical conditions that may interfere with participation in the study or potentially affect the interpretation of the study data. - 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 - QTcF > 450 msec for males and > 470 msec for females on the screening ECG - A past medication 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 compliance with an antihypertensive regimen) - Pregnant and/or breastfeeding. Pregnant women are excluded from this study because sonidegib is an Hh inhibitor 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 sonidegib, breastfeeding should be discontinued if the mother is treated with sonidegib. |
| 9 | NCT01781975 | completed | 0.4847285747528076 | phase 2 | ['diabetes mellitus, type i', 'diabetes mellitus, insulin-dependent, 1', 'type 1 diabetes mellitus', 'insulin-dependent diabetes mellitus 1', 'iddm'] | ["['E10.3521', 'E10.3522', 'E10.3523', 'E10.3529', 'E10.3531', 'E10.3532', 'E10.3533']", "['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']", "['E10.65', 'E10.9', 'E10.21', 'E10.36', 'E10.41', 'E10.42', 'E10.44']", "['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']"] | ['imatinib mesylate', 'placebo (for imatinib mesylate)'] | ['CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Males and females age 12-45 years of age who meet the ADA standard T1DM criteria1. Positive for at least one islet cell autoantibody. Initial enrollment will be for subjects ages 18-45, with the goal to lower the age down to 12 upon acceptable safety review and prospect of benefit for this initial older cohort. - Diagnosis of T1DM within 100 days of Visit 0. - Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT. - Participants of childbearing age who are sexually active must agree to use an effective form of birth control (e.g., barrier method, oral contraception, or surgery). For females, these contraceptive measures must be maintained throughout the study; for males these measures must be followed for a minimum of 3 months after discontinuation of imatinib therapy. Exclusion Criteria: - Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof. - Leukopenia (<3,000 leukocytes/μL), neutropenia (<1,500 neutrophils/μL), or thrombocytopenia (<125,000 platelets/μL). - Low Hemoglobin (baseline hemoglobin below lower limit of normal) - Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions - Any sign of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV, CMV, or toxoplasmosis), or screening laboratory evidence consistent with a significant chronic active infection (such as positive for HIV, PPD, or HBSAg). Significant acute infections must be resolved before treatment may commence, e.g., acute respiratory tract, urinary tract, or gastrointestinal tract infections. - Anticipated ongoing use of diabetes medications other than insulin that affect glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, glucagon-like peptide 1 (GLP-1) mimetics, dipeptidyl peptidase IV (DPP-IV) inhibitors, or amylin. - Prior or current treatment that is known to cause a significant, ongoing change in the course of T1DM or immunologic status, including high-dose inhaled, extensive topical or systemic glucocorticoids. - Evidence of liver dysfunction, with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 times the upper limit of normal persistent for 1 week or greater. - Evidence of renal insufficiency as indicated by serum creatinine > 1.2 times the upper limit of normal and confirmed in a repeat test at least one week apart. Evidence of clinically significant metabolic bone disease (except adequately treated rickets). - Females who are pregnant at the time of screening or unwilling to defer pregnancy during the 24-month study period. - Prior treatment with imatinib or related tyrosine kinase inhibitor. - Unable to avoid medications that affect CYP3A4: either inducers that may decrease imatinib levels, or inhibitors that may increase drug concentrations. (Refer to section 1.5.1.12 for a complete list of inducers and inhibitors.) - Height standard deviation score ≥2 standard deviations below mean - Any sign of QT prolongation on Visit -1 noted on ECG (> 450 ms in males and > 470 ms in females) - Known coagulation disorders or use of anticoagulants - Current and anticipated on-going treatment with drugs that may increase or decrease imatinib plasma concentrations (CYP3A4 family inhibitors or inducers) or drugs that may have their plasma concentration altered by imatinib (drugs metabolized by CYP3A4/5 and CYP2D6). - Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results. | |
| 10 | NCT01788280 | withdrawn | unable to get materials from ge, study not proceeding and never opened to accrual | 0.37640929222106934 | phase 2 | ['glioblastoma multiforme (gbm)'] | ["['L51.0', 'L51.8', 'L51.9']"] | ['fluciclitite , pet imaging, and bevacizumab'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Patients must be 18 years or older for inclusion in this research study. There is inadequate experience with the safety of [18F] Fluciclatide (GE [18F]AH111585) in children and therefore this radiopharmaceutical should not be used in patients under the age of 18. - The patient must have a histologically proven GBM, and are scheduled to be treated with Avastin therapy. - Patient has a tumor volume of > 2.0 cm in greatest diameter is required to assess response to therapy. - An anatomic imaging study (MRI of the brain) must be current and have been obtained within 28 days prior to the research PET imaging studies. - Patients must agree to have clinical and radiographic endpoints and the results of histopathologic tissue analysis and other laboratory information entered into a research database, as evidenced by signing the informed consent form. - All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines. - If patient is female, she must be postmenopausal for a minimum of one year, surgically sterile, or has been confirmed not to be pregnant by serum pregnancy test performed within 48 hours prior to research PET imaging. - Patient must not be lactating. - Pre-treatment laboratory tests for patients receiving [18F] Fluciclatide (GE [18F]AH111585) must be performed within 21 days prior to study entry. - These laboratory tests must be less than 4.0 times below or above the upper or lower limit range for the respective laboratory test for entry into the study (unless not medically or clinically relevant). - For those patients receiving coumadin or another anticoagulant the upper limit for prothrombin time or partial thromboplastin time must not exceed 6 times the upper limit of the normal range. - Urinalysis abnormalities will not preclude the patient from being enrolled and studied. - The laboratory testing will include liver enzymes (SGOT, SGPT, ALK Phos, GGT, LDH), bilirubin (total), amylase, albumin, serum electrolytes (sodium, potassium, chloride, HCO3, calcium, creatinine, urea nitrogen, glucose) CBC with platelets prothrombin time, partial thromboplastin time, BUN, creatinine and urinalysis (screening only). Exclusion Criteria: - Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion. - Adult patients who require monitored anesthesia for PET scanning. - Patients who are too claustrophobic to undergo MRI or PET imaging. - Patients with a calculated GFR of less than 30 ml/min will be excluded from the study. For a GFR between 30-60 ml/min the MRI will be possible (using half the usual administered dose of contrast) at the discretion of the study doctor. If the patient does not wish to undergo an MRI due to their renal function they will be excluded from the study. - Patients known to be HIV positive. This is due to the unknown potential toxicities of Fluciclatide in HIV positive patients. - Patients who cannot undergo MRI imaging due to MRI exclusion criteria |
| 11 | NCT01806571 | completed | 0.41427475214004517 | phase 2 | ['untreated adult acute myeloid leukemia'] | ["['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']"] | ['cytarabine', 'daunorubicin hydrochloride', 'nilotinib'] | ['ClCCN(CCCl)P1(=O)NCCCO1', '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(C)=O)C(O)=C1C2=O', 'CC1=CN(C=N1)C1=CC(NC(=O)C2=CC=C(C)C(NC3=NC=CC(=N3)C3=CN=CC=C3)=C2)=CC(=C1)C(F)(F)F'] | Inclusion Criteria: - Untreated, histological confirmed acute myeloid leukemia (AML) based on World Health Organization (WHO) 2008 criteria with Kit expression (cluster of differentiation [CD] 117) of myeloblasts >= 20% by flow cytometry from bone marrow aspirate at diagnosis - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Magnesium within normal limits (WNL) - Potassium WNL - Phosphorus WNL - Serum amylase =< 1.5 x upper limit of normal (ULN) - Serum lipase =< 1.5 x ULN - Total bilirubin =< 1.5 x ULN (does not apply to patients with isolated hyperbilirubinemia [e.g., Gilbert's disease], in that case direct bilirubin should be =< 2 x ULN) - Alkaline phosphatase =< 3 x ULN - Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN - Creatinine =<1.5 x ULN - Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only - Provide informed written consent - Willing to return to consenting Mayo Clinic (Mayo Clinic's campus in Rochester, Mayo Clinic's campus in Arizona, or Mayo Clinic's campus in Florida) institution for follow-up during the active monitoring phase of the study - Willing to provide bone marrow aspirate and blood samples for correlative research purposes Exclusion Criteria: - Any of the following because this study involves investigational agent(s) whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown - Pregnant women - Nursing women - Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 3 months after completion of study treatment - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens - Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements - Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm - Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix - Previous treatment with chemotherapy or any other tyrosine kinase inhibitor for a hematological disorder; Exceptions: patients with prior diagnosis of myelodysplastic syndrome (MDS) and/or treatment with hypomethylating agent (azacytidine or decitabine) are not excluded, prior hydroxyurea allowed - Impaired cardiac function including any one of the following: - Inability to monitor the QT interval on electrocardiogram (ECG) - Congenital long QT syndrome or a known family history of long QT syndrome - Clinically significant resting brachycardia (< 50 beats per minute) - Corrected QT (QTc) > 450 msec on baseline ECG; if QTc > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc - Myocardial infarction =< 12 months prior to starting study - Other clinically significant uncontrolled heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension) - History of or presence of clinically significant ventricular, atrial tachyarrhythmias or ejection fraction cutoff - Left ventricle ejection fraction < 45% - History of, congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias - Patients currently receiving treatment with strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors and treatment that cannot be either discontinued or switched to a different medication prior to starting study drug; patients receiving any medications or substances that are strong or moderate inhibitors of CYP3A4 - Use of the following strong or moderate inhibitors is prohibited < 7 days prior to registration - Strong inhibitors of CYP3A4/5 > 5-fold increase in the plasma area under the curve (AUC) values or more than 80% decrease in clearance - Boceprevir (Victrelis) - Clarithromycin (Biaxin, Biaxin XL) - Conivaptan (Vaprisol) - Grapefruit juice - Indinavir (Crixivan) - Itraconazole (Sporanox) - Ketoconazole (Nizoral) - Lopinavir/ritonavir (Kaletra) - Mibefradil - Nefazodone (Serzone) - Nelfinavir (Viracept) - Posaconazole (Noxafil) - Ritonavir (Novir, Kaletra) - Saquinivir (Fortovase, Invirase) - Telaprevir (Incivek) - Telithromycin (Ketek) - Voriconazole (Vfend) - Moderate inhibitors of CYP3A4/5 > 2-fold in the plasma AUC values or 50-80% decrease in clearance - Amprenavir (Agenerase) - Aprepitant (Emend) - Atazanavir (Reyataz) - Ciprofloxacin (Cipro) - Darunavir (Prezista) - Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Taztia XT, Tiazac) - Erythromycin (Erythrocin, E.E.S. , Ery-Tab, Eryc, EryPed, PCE) - Fluconazole (Diflucan) - Fosamprenavir (Lexiva) - Imatinib (Gleevec) - Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM) - Receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited =< 7 days prior to registration - Strong inducers of CYP3A4/5 > 80% decrease in AUC - Avasimibe - Carbamazepine (Carbatrol, Epitol, Equetro, Tegretol, Tegretol-XR) - Phenytoin (Dilantin, Phenytek) - Rifampin (Rifadin) - St. John's wort - Moderate inducers of CYP3A4/5 50-80% decrease in AUC - Bosentan (Tracleer) - Efavirenz (Sustiva) - Etravirine (Intelence) - Modafinil (Provigil) - Nafcillin - Nevirapine (Viramune) - Phenobarbital (Luminal) - Rifabutin (Mycobutin) - Troglitazone - Patients currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug - Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery) - Acute or chronic pancreatic disease - Known cytopathologically confirmed central nervous system (CNS) infiltration - Acute or chronic liver disease or severe renal disease considered unrelated to the cancer - History of significant congenital or acquired bleeding disorder unrelated to cancer - Major surgery =< 4 weeks prior to registration of the study or who have not recovered from prior surgery - Treatment with other investigational agents =< 14 days of registration - Diagnosis of AML-M3 (or acute promyelocytic leukemia) | |
| 12 | NCT01812616 | completed | 0.41304293274879456 | 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. | |
| 13 | NCT01825122 | completed | 0.4856201410293579 | phase 2 | ['smoking cessation'] | ["['Y36.881S', 'Y36.891S', 'Y36.880S', 'Y36.881A', 'Y36.881D', 'Y36.890S', 'Y36.891A']"] | ['nadolol', 'placebo'] | ['CC(C)(C)NCC(O)COC1=CC=CC2=C1C[C@H](O)[C@H](O)C2', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: Potential study participants will be referred from approved smoking cessation programs or be willing to enter a smoking cessation program administered by the participating sites. Individuals who meet all of the following criteria at Visit 1 are eligible for enrollment as study participants: 1. Active cigarette-smoking males and females between the ages of 18-70 with chronic cough associated with long-term smoking, with or without airflow obstruction, including Non-obstructive chronic bronchitis (NCB) or physician-diagnosed COPD (chronic bronchitis dominant), as defined by the American Thoracic Society. 2. Committed desire to quit smoking in conjunction with participation in an approved smoking cessation program administered by the participating sites. Enrollment in the smoking cessation program must take place prior to Visit 3 (third dose escalation visit). 3. Diagnosis of COPD (chronic bronchitis dominant) or NCB, or presenting with chronic cough associated with long-term smoking. 4. Pre-bronchodilator FEV1 greater than 55% of predicted 5. Baseline blood pressure ≥ 110/65mm Hg 6. Baseline heart rate ≥ 60 beats/min. 7. Smoking at least 10 cigarettes per day prior to participation in the approved smoking cessation program. 8. Self-reported prior failure(s) to quit smoking during participation in a smoking cessation program. 9. Able to complete diary cards and comply with study procedures. 10. Females of childbearing age may participate only if they have a negative pregnancy test, are non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study. Exclusion Criteria: Subjects who meet ANY of the following criteria are not eligible for enrollment: 1. Diagnosis of asthma, cystic fibrosis, or PiZZ emphysema 2. Inability or unwillingness to give written informed consent 3. History of upper/lower respiratory tract infection, COPD exacerbation requiring systemic steroids, antibiotics, and or ER visit or urgent care within 6 weeks of Visit 1 4. History of adverse reaction or allergy to nadolol 5. History of neurological, hepatic, renal, or other medical conditions that may interfere with the interpretation of data or the patient's participation in the study or may increase safety concerns 6. History of cardiovascular diseases including uncontrolled hypertension (BP >160/100), ischemic heart disease, congestive heart failure (NYHA III or IV), valvular heart disease or cardiomyopathy 7. Known allergy or sensitivity to atropine or ipratropium bromide 8. Documented or self-reported current history of alcoholism or drug abuse 9. Participation in another research trial within 30 days of starting this trial 10. Unwillingness or inability to comply with study procedures 11. Inability to swallow the study medication 12. Pregnant or nursing 13. Current use of any OTC remedies containing pseudoephedrine, ephedrine-based or containing dietary or herbal supplements. 14. Scheduled for surgery requiring general anaesthesia 15. Referred for smoking cessation without serious commitment to quit | |
| 14 | NCT01827358 | completed | 0.6284596920013428 | phase 2 | ['staphylococcal infection'] | ["['G00.3', 'M00.09', 'A05.0', 'M00.08', 'L00', 'M00.00', 'M00.011']"] | ['mupirocin calcium', 'mupirocin calcium'] | ['C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@H]1CO[C@@H](C\\C(C)=C\\C(=O)OCCCCCCCCC(O)=O)[C@H](O)[C@@H]1O', 'C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@H]1CO[C@@H](C\\C(C)=C\\C(=O)OCCCCCCCCC(O)=O)[C@H](O)[C@@H]1O'] | Inclusion Criteria: 1. Currently admitted to a NICU or ICU at a participating site 2. Chronological age less than 24 months 3. Evidence of colonization with SA (MRSA or MSSA) based on a positive nasal surveillance culture. Randomization must occur within 7 days (168 hours) of when the site's laboratory reports the first SA positive nasal surveillance swab 4. The attending neonatologist/ intensivist anticipates that the infant will remain in the ICU for a minimum of 14 days after enrollment 5. Parent or legal guardian agrees that the infant will not participate in a research trial involving the administration of an investigational drug for 14 days following enrollment Exclusion Criteria: 1. Receipt of an investigational drug as part of a research trial within the past 14 days 2. Previously enrolled and participated in this trial 3. Has an active or previous SA infection 4. Currently receiving topical or intranasal mupirocin 5. Has a rash in an area to which mupirocin will be directly applied 6. Has any of the following congenital abnormalities: --A congenital skin disorder (i.e. - epidermolysis bullosa, icthyosis) --An opened neural tube defect --Confirmed or suspected choanal atresia --Any of the following abdominal wall defects: wound dehiscence, gastroschisis, open abdominal wound (small abdominal wall defects such as ostomy sites or peritoneal drain sites are not exclusionary) 7. Is nasally intubated 8. Known hypersensitivity to the trial product or its constituents 9. Known or suspected immune deficiency. Infants born to HIV-seropositive mothers with the following risk factors for intrapartum transmission will not be eligible to participate: --Mother's most recent viral load within the past 3 months was > 1,000 copies/ml or --Mother's viral load is not known or has has not been measured in the past 3 months. 10. Any other condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant or would render the participant unable to comply with the protocol | |
| 15 | NCT01836289 | withdrawn | too difficult to recruit given new crohn's medications approved | 0.3845057487487793 | 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 |
| 16 | NCT01858662 | terminated | due to poor recrutment | 0.31997665762901306 | phase 2 | ['metastatic colorectal cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['5-fluorouracile', 'leucovorin l', 'oxaliplatin', 'irinotecan', 'cetuximab'] | ['[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', 'CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O', '[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: 1. Female or male patients with at least 18 years at the time the informed consent is signed 2. ECOG performance status 0 or 1 3. Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type RAS and B-RAF tumor status. 4. Patients with potentially resectable metastatic disease at diagnosis and for whom a chemotherapy first in a curative intent is recommended . Resectability could be planed in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors. 5. Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC. 6. Extra hepatic metastatic location is limited to 1 site. 7. Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion. 8. Adequate haematological, renal and hepatic function as follows: Haematological: haemoglobin >9g/dl Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal: Creatinine< 1.5 x ULN (Upper Limit of Normal) Hepatic: Bilirubin < or equal 1.5 X ULN AST (Aspartate Aminotransferase),and ALT (Alanine Aminotransferase)< or equal 5 x ULN, Phos Alc< or equal 5 x ULN 9. Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception. 10. Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception. 11. Life expectancy of at least 3 months without any active treatment. Exclusion Criteria: - 1.Definitively non resectable mCRC at diagnosis - 2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion. - 3.Prior utilization of cetuximab, panitumumab (or other anti-EGFR (epidermal growth factor receptor)therapy). - 4.Previous radiotherapy delivered to the upper abdomen. - 5 Non mesurable disease( RECIST 1.1 criteria) - 6.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment. - 7.Prior major liver resection: remnant liver < 50% of the initial liver volume. - 8.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol. - 9.Concurrent central nervous systems metastases - 10.Peripheric neuropathy ≥ grade 2. - 11.Interstitial lung disease - 12.Pregnant or breast feeding. - 13.The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix. |
| 17 | NCT01883362 | completed | 0.46913382411003113 | phase 2 | ['acute myeloid leukemia'] | ["['C92.A1', 'C92.A2', 'C92.61', 'C92.62', 'C92.A0', 'C92.60']"] | ['midostaurin'] | ['CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1'] | Inclusion Criteria: - Patients between 18 and 60 years of age - Patients with ECOG Performance Status of < 2 - Patients with a documented unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia). - Patients with a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation) - Patients who undersent allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria had to be met: HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch allowed • Patients who had received a conditioning regimen which included one of the following: Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI) Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy) • Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first dose of midostaurin to start no earlier than 28 days post-HSCT); ANC >1000µL, platelets ≥20,000 without platelet transfusion Exclusion Criteria: - Patients who failed prior attempts at allogeneic HSCT - Patients who had received an autologous transplant - Patients with Acute GVHD Grade III-IV - Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis. - Impaired cardiac function including any of the following: - Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes were not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc. - Patients with congenital long QT syndrome - History or presence of sustained ventricular tachycardia - Any history of ventricular fibrillation or torsades de pointes - Bradycardia defined as HR. < 50 bpm - Right bundle branch block + left anterior hemiblock (bifascicular block) - Patients with myocardial infarction or unstable angina < 6 months prior to starting study - Congestive Heart Failure NY Heart Association class III or IV - Patients with an ejection fraction < 45% assessed by MUGA or ---ECHO within 28 days prior to starting study cycle 1 (of midostaurin or control group) - Patients with any pulmonary infiltrate including those suspected to be of infectious origin (unless resolves to ≤ Grade 1 within screening timeframe) - Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers other than those required for GVH or infection prophylaxis or treatment Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used highly effective methods of contraception during dosing and for 30 days after treatment completion | |
| 18 | NCT01900730 | terminated | due to low accrual | 0.48925867676734924 | phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['placebo', 'valproic acid (vpa)'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'C[N+](C)(C)C[C@H](O)CC([O-])=O'] | Inclusion Criteria: 1. Patients with symptomatic pleural effusion requiring the presence of an IPC or new placement of an IPC. 2. Pathologic documentation of breast cancer. 3. Performance status 0 to 3 (ECOG scale). 4. Signed informed consent. 5. Subject must be female or male age 18 years or over. 6. At least one prior line of chemotherapy in the metastatic setting. 7. Positive effusion cytology. Exclusion Criteria: 1. Other prior malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer) from which the patient has been disease-free for at least two years. 2. Laboratory results sustained at: Neutrophils less than 1.5 × 109/L ; Serum bilirubin >1.5 x the upper limit of reference range (ULRR); Serum creatinine >1.5 x ULRR or creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula). 3. Patients with a history of existing hypercalcemia, hypocalcemia, hypermagnesemia or hypomagnesemia that is not corrected despite supplementation. Known Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULRR or alkaline phosphatase (ALP) >2 x ULRR, or > 4x ULRR if judged by the investigator to be related to liver metastases. 4. Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension or renal diseases. 5. Diagnosis of an infection requiring IV antibiotics 14 days prior to registration. 6. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 7. Women who are currently pregnant or breast feeding. 8. Known hypersensitivity to VPA, valproate sodium, disodium valproate, or any ingredient in the respective formulation. 9. Known urea cycle disorders based on history. 10. Known HIV infection based on history. 11. Active or recent pancreatitis (within last 6 months). 12. Any of the following interventions on the affected hemithorax: prior IPC, prior chest tube placement, history of chemical or mechanical pleurodesis, history of thoracotomy within 4 weeks and incompletely healed surgical incision before randomization. 13. Evidence of empyema or history of empyema of the affected hemithorax. 14. Non-correctable bleeding diathesis. 15. Clinical evidence of skin infection at the potential site of IPC placement. 16. Patients currently taking valproic acid. 17. History of hepatitis or liver disease. 18. The following drugs will not be administered concurrently with VPA: Carbapenem antibiotics; Clonazepam; Topiramate; Felbamate; Lorazepam; Barbiturates; Barbiturates; CarBAMazepine; ChlorproMAZINE; Ethosuximide; GuanFACINE; LamoTRIgine; MethylfolateOXcarbazepine; Paliperidone; Phenytoin; Primidone; Protease Inhibitors; Rifampin; Risperidone; Rufinamide; Salicylates; Temozolomide; Tricyclic Antidepressants; Vorinostat; Zidovudine. 19. History of seizures. |
| 19 | NCT01920555 | completed | 0.46632978320121765 | phase 2 | ['treatment resistant depression'] | ["['F32.A', 'F53.0', 'P91.4', 'Z13.31', 'Z13.32']"] | ['ketamine', 'ketamine', 'ketamine', 'ketamine', 'placebo midazolam'] | ['CC1=CC(O)=CC(C)=C1Cl', 'CC1=CC(O)=CC(C)=C1Cl', 'CC1=CC(O)=CC(C)=C1Cl', 'CC1=CC(O)=CC(C)=C1Cl', 'CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12'] | Inclusion Criteria: - Male or female, 18-70 years old. - Able to read, understand, and provide written, dated informed consent prior to screening. - Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently experiencing a Major Depressive Episode (MDE) of at least eight weeks in duration, prior to screening. - Has a history of TRD during the current MDE. - Meet the threshold on the total MADRS score of greater than or equal to 20 at both screening and baseline visits (Day -7/-28 and Day 0), as confirmed by the remote centralized MGH CTNI rater between the screen visit and the baseline visit. - In good general health - For female participants, status of non-childbearing potential or use of an acceptable form of birth control - Body mass index between 18-35 kg/m2 - Concurrent psychotherapy will be allowed if the type and frequency of the therapy has been stable for at least three months prior to screening and is expected to remain stable during participation in the study - Concurrent hypnotic therapy will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable during the course of the subject's participation in the study. Exclusion Criteria: - Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study - Female that is pregnant or breastfeeding - Female with a positive pregnancy test at screening or baseline - History during the current MDE of failure to achieve a satisfactory response to >7 treatment courses of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration during the current episode - Total MADRS score of <20 at the screen or baseline visits, or as assessed by the remote, independent MGH CTNI rater and reported to the site - Current diagnosis of a Substance Use Disorder (Abuse or Dependence) with the exception of nicotine dependence, at screening or within 6 months prior to screening - Current Axis I disorder that is the principal focus of treatment and MDD the secondary focus of treatment for the past 6 months or more - History of bipolar disorder, schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes - History of eating disorders within five years of screening - Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant at any time within 6 months prior to screening - Subject is considered at significant risk for suicidal behavior during the course of their participation in the study - Has failed to respond to electroconvulsive therapy (ECT) during the current depressive episode - Has received vagus nerve stimulation (VNS) at any time prior to screening - Has dementia, delirium, amnestic, or any other cognitive disorder - Has a clinically significant abnormality on the screening physical examination - Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation - Current episode of: 1. Hypertension, Stage 1 as defined by a systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90 mmHg at screening on two of three measurements (standing and supine) at least 15 minutes apart. 2. Hypertension, Stage 1 as defined by a systolic blood pressure ≥155 mmHg or diastolic blood pressure ≥99 mmHg at the Baseline Visit (Visit 1) within 1.5 hours prior to randomization on two of three measurements (standing and supine) at least 15 minutes apart. 3. Recent myocardial infarction (within one year) or a history of myocardial infarction. 4. Syncopal event within the past year. 5. Congestive heart failure (CHF) New York Heart Association Criteria >Stage 2 6. Angina pectoris. 7. Heart rate <50 or >105 beats per minute at screening or randomization (Baseline Visit). 8. QTcF (Fridericia-corrected) ≥450 msec at screening or randomization (Baseline Visit). - Current history of hypertension, or on antihypertensives for the purpose of lowering blood pressure, who have either had an increase in antihypertensive dose or increase in the number of antihypertensive drugs used to treat hypertension over the last 2 months. - Chronic lung disease excluding asthma. - Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system disorder, epilepsy, mental retardation, or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system, or a history of significant head trauma within the past 2 years - Presents with any of the following lab abnormalities: 1. Thyroid stimulating hormone outside of the normal limits and clinically significant as determined by the investigator. Free thyroxine (T4) levels may be measured if TSH level is high. Subject will be excluded if T4 level is clinically significant. 2. Patients with diabetes mellitus fulfilling any of the following criteria: i. Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening ii. Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus related illness in the past 12 weeks iii. Not under physician care for diabetes mellitus iv. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks. c. Any other clinically significant abnormal laboratory result (as determined after evaluation by study investigator and MGH CTNI medical monitor) at the time of the screening exam. - History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than 2 months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least 2 months or more prior to screening are eligible for enrollment.) - History of hyperthyroidism which was treated (medically or surgically) less than six months prior to screening - Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation - History of positive screening urine test for drugs of abuse at screening - Patients with exclusionary laboratory values, or requiring treatment with exclusionary concomitant medications - Patients on exclusionary concomitant psychotropic medications, the half-life of which would not allow sufficient time for patients to have been free of the medication post-taper for five half-lives within the maximum screening period (28 days). - Patient who have participated in studies of ketamine or AZD6765 or other NMDA receptor antagonists for depression and received active treatment. - Patients with narrow angle glaucoma - Patients with a lifetime history of PCP/Ketamine drug use - Liver Function Tests higher than 2.5 times upper limit of normal | |
| 20 | NCT01923168 | completed | 0.40531161427497864 | phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['alpelisib', 'buparlisib', 'placebo'] | ['[H][C@]1(CCCN1C(O)=NC1=NC(C)=C(S1)C1=CC(=NC=C1)C(C)(C)C(F)(F)F)C(O)=N', 'N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. Patient is an adult, female ≥ 18 years old at the time of informed consent 2. Patient has a histologically and/or cytologically confirmed diagnosis of breast cancer 3. Patient is postmenopausal. 4. Patient has T1c-T3, any N, M0, operable breast cancer 5. Patients must have measurable disease 6. Patient has diagnostic biopsy available for the analysis of PIK3CA mutation and Ki67 level. 7. Patient has estrogen-receptor and/or progesterone positive breast cancer as per local laboratory testing 8. Patient has HER2 negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0 or 1+ as per local laboratory testing Exclusion Criteria: 1. Patient has locally recurrent or metastatic disease 2. Patient has received any systemic therapy (e.g. chemotherapy, targeted therapy, immunotherapy) or radiotherapy for current breast cancer disease before randomization. 3. Patient with type 1 diabetes mellitus or not adequately controlled type 2 diabetes mellitus 4. History of acute pancreatitis within 1 year of study entry 5. Uncontrolled hypertension | |
| 21 | NCT01925261 | completed | 0.43514251708984375 | phase 2 | ['knee osteoarthritis'] | ["['M17.9', 'M17.0', 'M17.10', 'M17.11', 'M17.12', 'M17.2', 'M17.30']"] | ['tpx-100 50mg', 'tpx-100 100mg', 'tpx-100 200mg', 'tpx-100 20mg', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. Age ≥ 25 and ≤ 75 2. Patello-femoral osteoarthritis of both knees of mild to moderate severity with intact meniscus and ligamentous stability (cruciate and collateral ligaments) - Clinically, as determined by screening questionnaire and judgment of the Principal Investigator (may be supported by imaging studies of knees); confirmed by centrally read screening MRI of both knees indicating ICRS Grade 1-3, or ICRS Grade 4 with only focal defects, no greater than 1 cm. - Meniscus intact (MRI degenerative signal up to and including grade II acceptable) - Cruciate and collateral ligament stability as defined by clinical examination 3. Able to read, understand, sign and date the subject informed consent 4. Willingness to use only acetaminophen as the primary analgesic (pain-relieving) study medication. The maximum dose of acetaminophen must not exceed 4 grams/day (4000 mg per day). 5. Willingness to use only hydrocodone/acetaminophen for breakthrough pain during the injection period (through study day 30). 6. Willingness not to use non-steroidal anti-inflammatory drugs (NSAIDS) such as aspirin, ibuprofen, naproxen for the first 30 days of the study. 7. Female subjects of child bearing potential who are sexually active (non-abstinent) must agree to and comply with using 2 highly effective methods of birth control (oral contraceptive, implant, injectable or indwelling intrauterine device, condom with spermicide, or sexual abstinence) while participating in the study. Exclusion Criteria: 1. Contraindication to MRI, including: metallic fragments, clips or devices in the brain, eye, or spinal canal; implanted devices that are magnetically programmed; weight > 300 lbs.; moderate or severe claustrophobia; previous intolerance of MRI procedure 2. ICRS grade greater than Grade 3, or Grade 4 focal defects greater than 1 cm, as confirmed by centrally-read screening MRI 3. MRI evidence of inflammatory or hypertrophic synovitis 4. Prior surgery in the knees, excluding procedures for debridement only (no microfracture) 5. Joint replacement or any other knee surgery planned in the next 12 months 6. History of rheumatoid arthritis, psoriatic arthritis, or any other autoimmune or infectious cause for arthritis 7. Knee effusion >2+ on the following clinical scale: - Zero = No wave produced on downstroke - Trace = Small wave on medial side with downstroke - 1+ = Larger bulge on medial side with downstroke - 2+ = Effusion spontaneously returns to medial side after upstroke (no downstroke necessary) - 3+ = So much fluid that it is not possible to move the effusion out of the medial aspect of the knee 8. Last viscosupplementation (e.g. Synvisc® or similar hyaluronic acid product) injected into either knee < 3 months before screening 9. Last intra-articular knee injection of corticosteroids < 2 months before screening 10. Use of any steroids (except inhaled corticosteroids for respiratory problems) during the previous month before screening 11. Known hypersensitivity to TPX-100 12. Known hypersensitivity to acetaminophen or hydrocodone 13. History of arthroscopy in either knee in the last 3 months before screening 14. History of septic arthritis, gout or pseudo-gout, of either knee in previous year before screening 15. Clinical signs of acute meniscal tear (locking, new acute mechanical symptoms consistent with meniscal tear) 16. Patellar chondrocalcinosis on X-Ray 17. Skin problem, rash or hypersensitivity, affecting either knee at the injection site 18. Bleeding problem, platelet or coagulation deficiency contraindicating, in the doctor's opinion, any intra-articular injection 19. Active systemic infection 20. Current treatment or treatment within the previous 2 years prior to the Screening Visit for any malignancy except basal cell or squamous cell carcinoma of the skin, unless with specific written permission is provided by the Sponsor's medical monitor 21. Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the entire study period 22. Participation in other clinical osteoarthritis drug studies within one year prior to screening 23. Currently taking Paclitaxel (mitotic inhibitor), and or Natalizumab (anti-integrin monoclonal antibody). 24. History of significant liver disease or consumption of more than 3 alcoholic drinks a day. (Definition of one alcoholic drink: 12-ounces of beer, 8-ounces of malt liquor, 5-ounces of wine, 1.5-ounces or a "shot" of 80-proof distilled spirits or liquor such as gin, rum, vodka, or whiskey). | |
| 22 | NCT01928927 | completed | 0.6199096441268921 | phase 2 | ['hiv-1 infection'] | ["['B20', 'Z71.7', 'O98.72', 'Z21', 'O98.73', 'R75', 'Z11.4']"] | ['telmisartan'] | ['CCCC1=NC2=C(C=C(C=C2C)C2=NC3=CC=CC=C3N2C)N1CC1=CC=C(C=C1)C1=CC=CC=C1C(O)=O'] | Step 1 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 Step 1 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, or plasma HIV-1 RNA viral load >2000 copies/mL on two occasions. - On antiretroviral therapy (ART) continuously for ≥48 weeks prior to Step 1 entry. - Documentation of HIV-1 RNA <50 copies/mL at screening, performed by any US laboratory that has a CLIA certification or its equivalent. - At least one HIV-1 RNA level <200 copies/mL in the 48 weeks prior to Step 1 entry (not including the screening). - No change in ART regimen in the 12 weeks prior to Step 1 entry (except as noted below). NOTE: Modifications of ART dosing during the 12 weeks prior to Step 1 entry are permitted. In addition, the change in formulation (eg, from standard formulation to fixed dose combination or single tablet regimen) is allowed within 12 weeks of Step 1 entry. A within-class single drug substitution (eg, switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 12 weeks of Step 1 entry, with the exception of a switch from any other NRTI to abacavir. No other changes in ART in the 12 weeks prior to Step 1 entry are permitted. - No active plan to change ART for the 48-week study duration. - Body mass index (BMI) 20-35 kg/m^2. - For females of reproductive potential, negative serum or urine pregnancy test within 3 days prior to Step 1 entry. - Ability and willingness of subject or legal guardian/representative to provide informed consent. - Willingness to undergo the Step 1 entry and week 48 lymphoid and adipose tissue biopsies. Step 2 Inclusion Criteria: - Entry lymphoid tissue and adipose tissue specimen for assay of the primary endpoint has been obtained. (Prior to Letter of Amendment #2, 11/19/14) - (Letter of Amendment #2, 11/19/14) Entry lymphoid tissue and adipose tissue specimens for assay of the primary endpoint have been obtained, entered into the ACTG's Laboratory Data Management System (LDMS), and confirmed by the protocol team as adequate for endpoint determination. NOTE: If the lymph node specimen is determined by the protocol team to be inadequate for endpoint determination despite the interventions summarized in LOA #2, the participant will be permitted to enroll if adequate adipose tissue is obtained. However, as change in lymph node fibrosis remains one of the primary endpoints of this study, it is critical that every effort be made to obtain an adequate sample while still trying to minimize complication rates. - Willingness to undergo the week 48 lymphoid and adipose tissue biopsies. (Prior to Letter of Amendment #2, 11/19/14) - (Letter of Amendment #2, 11/19/14) Willingness to undergo the week 48 lymphoid and adipose tissue biopsies. NOTE: A week 48 lymph node biopsy is not required if the Step 1 lymph node specimen was deemed inadequate as noted in 4.3.1. Week 48 adipose tissue biopsies will still be required for these participants. Step 1 Exclusion Criteria: - More than one HIV-1 RNA >200 copies/mL in the 48 weeks prior to Step 1 entry. - One HIV-1 RNA 200-500 copies/mL in the 24 weeks prior to Step 1 entry that is not immediately preceded and followed by HIV-1 RNA <50 copies/mL. NOTE: The preceding viral load <50 copies/mL may be >24 weeks prior to Step 1 entry. - Confirmed systolic blood pressure >160 mmHg or <100 mmHg or diastolic blood pressure >100 mmHg. - Known untreated renal artery stenosis. - Known cirrhosis or severe liver disease (eg, ascites, encephalopathy, history of variceal bleeding). NOTE: Potential subjects with chronic hepatitis B or C virus infection with no known cirrhosis or severe liver disease may participate in the study, provided there are no plans to start therapy for hepatitis C infection during the 48-week study duration. - Unstable coronary artery disease/angina or decompensated congestive heart failure. - Either breastfeeding or pregnant within 24 weeks prior to Step 1 entry. - Use of thiazolidinediones or any angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in the 24 weeks prior to Step 1 entry. If the subject took either of these classes of medications for less than 2 weeks in the 24 weeks prior to Step 1 entry, the subject may enroll if 30 days have passed since the last dose. If the subject is diabetic and/or has a calculated glomerular filtration rate (GFR) <60mL/min, aliskiren-containing medications are also prohibited. - History of intolerance, other than cough, to any ARB or ACEi. - Use of anticoagulants other than aspirin 81 mg or 325 mg daily. NOTE: If the subject is on aspirin 81 mg or 325 mg daily and is willing/able to stop therapy for 7 days prior to the biopsy procedures, the subject may enroll. - Any known bleeding disorder or coagulopathy. - Projected need for daily potassium supplementation for ≥2 weeks during the study period. - The following laboratory values obtained within 30 days prior to Step 1 entry by any US laboratory that has a CLIA certification or its equivalent: - Absolute neutrophil count (ANC) ≤750 cells/mm^3 - Hemoglobin ≤10 g/dL - Platelet count ≤75,000/mm^3 - Calculated creatinine clearance (CrCl) <50 mL/min, as estimated by the Cockcroft-Gault equation - Aspartate aminotransferase (AST) (SGOT) >/=3x ULN (upper limit of normal) - Alanine aminotransferase (ALT) (SGPT) >/=3x ULN - Partial thromboplastin time (PTT) >1.2x ULN - Prothrombin time (PT) >1.2x ULN - Heritable connective tissue disorders (eg Ehlers-Danlos syndrome, osteogenesis imperfecta, Stickler syndrome, Marfan's syndrome). NOTE: Subjects with acquired/autoimmune chronic inflammatory diseases/connective tissue disorders who are clinically stable (in the opinion of the site investigator) and not on a prohibited medication may enroll with approval of the A5317 study chairs. - Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to Step 1 entry. - Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. - Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study. Step 2 Exclusion Criteria: - Any AE associated with the Step 1 entry biopsy that would exclude the subject from undergoing follow-up biopsy at week 48. | |
| 23 | NCT01930864 | unknown status | 0.372690349817276 | phase 2 | ['colorectal neoplasms', 'adenocarcinoma'] | ["['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']"] | ['metformin', 'irinotecan'] | ['CSCC[C@H](N)C(O)=O', 'CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O'] | Inclusion Criteria: - 18 years or older - Biopsy-proven colorectal adenocarcinoma - Ineligibility for curative intent therapy, e.g., surgery or radiation - Disease progression after oxaliplatin (either adjuvant or palliative), fluoropyrimidine (either adjuvant or palliative), irinotecan, and if Kras wild type a anti-EGFR therapy - Assessable disease according to RECIST v1.1 Exclusion Criteria: - known hypersensitivity to metformin or irinotecan - Uncontrolled Central nervous system metastasis - Acute or chronic severe infection | |
| 24 | NCT01933594 | completed | 0.45669397711753845 | 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. | |
| 25 | NCT01934192 | terminated | 0.6506646275520325 | phase 2 | ['gastroparesis'] | ["['K31.84']"] | ['gsk962040 50 mg', 'metoclopramide 10 mg', 'placebo ng', 'placebo iv'] | ['C[C@H]1CN(CC2=CC=C(CC(=O)N3CCC(CC3)NC3=CC=CC(F)=C3)C=C2)CCN1', 'CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[Na+].[Cl-]'] | Inclusion Criteria: - Age & Gender: Male or female between 18 and 85 years of age inclusive, at the time of obtaining the informed consent. - First admitted to participating ICU within the previous 48 hours. - Intubated and invasively mechanically ventilated - Indicated to receive early EN or are already receiving EN (subject must be on EN prior to receiving study treatment) - Have at least one of the following - Clinical evidence of cardiovascular dysfunction defined as the need for vasopressor agents (e.g. norepinephrine, epinephrine, vasopressin), >5 microgram/kg/min of dopamine, or >/= 50 microgram/min phenylephrine) for greater than or equal to 2 hours; - Poly-trauma with an injury severity score (ISS) >=15 points - Acute traumatic or non-traumatic brain injury Glasgow Coma Scale (GCS) <=12, prior to the initiation of sedation. Exclusion Criteria: - Subjects who are not expected to be in the ICU and alive for at least 48 hrs from point of screening. - Subjects with acute hepatitis (e.g. acute hepatitis B or C) or severe chronic liver disease (e.g. Child Pugh class C cirrhosis) will be excluded - Liver function tests: If Alanine aminotransferase (ALT) >=8x upper limit of normal (ULN); OR If ALT >5-8x ULN and bilirubin >2<=3 ULN or bilirubin >3x ULN (Include only if bilirubin <1.5xULN); OR If ALT <=5xULN and Bilirubin >3xULN (Include only if ALT <=3xULN and Bilirubin >2 <=3xULN) - Subjects who have received a gastric prokinetic agent in the previous 12 hours (e.g., erythromycin, azithromycin, metoclopramide, domperidone). - QT duration corrected for heart rate (QTc) >480 ms. QTcF is the recommended correction factor for all sites. If QT duration corrected for heart rate by Fridericia's formula (QTcF) is not possible to obtain or calculate, QT duration corrected for heart rate by Bazett's formula (QTcB) or machine or manual over read, may be obtained after consultation with the medical monitor. The QT correction formula used to determine inclusion and discontinuation should be the same throughout the study. - Use of strong Cyp3A4 inhibitors - Subjects who require renal replacement therapy or with an estimated glomerular filtration rate (GFR) of <30 mL/min byCockroft-Gault calculation). - Subjects who have a history of or who have undergone major esophageal or gastric surgery on this admission (major lower abdominal surgery will not result in exclusion unless this carries a contraindication to enteral feeding). - Subjects with an absolute contraindication to enteral nutrition e.g. subjects with ongoing bowel obstruction or perforation. - Subject has a gastric pacemaker - Pregnant or lactating females - 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. - Concurrent enrollment in other interventional study involving a novel (i.e.unapproved or experimental) chemical or biopharmaceutical entity. - Previous randomization in this study - Subjects for whom the reason for admission to ICU was an overdose (deliberate or accidental; medicinal product or not). - Exclusion to re-randomization: - Subjects with an untreated pheochromocytoma. - Subjects with a past history of a seizure disorder (e.g., epilepsy) and is currently receiving anti-epileptic treatment for their seizure disorder, ongoing refractory, or sustained seizure disorder (prophylactic use for head injury/isolated new seizure maintained on anti-seizure meds in ICU acceptable). - Subjects taking drugs likely to cause extrapyramidal reactions. | |
| 26 | NCT01936844 | completed | 0.4804231524467468 | phase 2/phase 3 | ['heart failure'] | ["['I50.814', 'I09.81', 'I50.82', 'I50.89', 'I50.9', 'T86.22', 'I11.0']"] | ['anakinra (high dose)', 'anakinra (standard dose)', 'placebo', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: All 5 criteria need to be met for enrollment of the patient in the study 1. Primary diagnosis of acute decompensated heart failure within the last 24 hours as evidenced by both of the following: 1. dyspnea or respiratory distress or tachypnea at rest or with minimal exertion 2. evidence of elevated cardiac filling pressure or pulmonary congestion (at least one of the conditions must be met); i. pulmonary congestion/edema at physical exam OR chest x-ray; ii. plasma Brain Natriuretic Peptide (BNP) levels ≥200 pg/mL; iii.invasive measurement of left ventricular end-diastolic pressure >18 mmHg or of pulmonary artery occluding pressure (wedge) >16 mmHg. 2. Left ventricular systolic dysfunction (LVEF<40%) during index hospitalization or prior 12 months. 3. Age ≥18 years old 4. Willing and able to provide written informed consent. 5. Screening plasma C-reactive protein levels >5 mg/L. Exclusion Criteria Subjects will not be eligible if they meet any of the following 15 exclusion criteria. 1. The primary diagnosis for admission is NOT decompensated heart failure, including diagnosis of acute coronary syndromes, hypertensive urgency/emergency, tachy- or brady-arrhythmias. 2. Concomitant clinically significant comorbidities that would interfere with the execution or interpretation of the study including but not limited to acute coronary syndromes, uncontrolled hypertension or orthostatic hypotension, tachy- or brady-arrhythmias, acute or chronic pulmonary disease or neuromuscular disorders affecting respiration. 3. Recent (previous 3 months) or planned cardiac resynchronization therapy (CRT), coronary artery revascularization procedures, or heart valve surgeries. 4. Previous or planned implantation of left ventricular assist devices or heart-transplant. 5. Chronic use of intravenous inotropes. 6. Recent (<14 days) use of immunosuppressive or anti-inflammatory drugs (not including Non-Steroidal Anti-Inflammatory Drugs [NSAIDs]). 7. Chronic inflammatory disorder (including but not limited to rheumatoid arthritis, systemic lupus erythematosus). 8. Active infection (of any type); 9. Chronic/recurrent infectious disease (including Hepatitis B virus [HBV], Hepatitis C virus [HCV], and HIV/AIDS). 10. Prior (within the past 10 years) or current malignancy. 11. Any comorbidity limiting survival or ability to complete the study. 12. End stage kidney disease requiring renal replacement therapy. 13. Neutropenia (<2,000/mm3) or Thrombocytopenia (<50,000/mm3). 14. Pregnancy. 15. Angina, arrhythmias, or electrocardiograph (ECG) changes that limit maximum exertion during cardiopulmonary exercise testing obtained during the baseline testing. | |
| 27 | NCT01937117 | active, not recruiting | 0.48557785153388977 | phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['trastuzumab', 'pertuzumab'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Female and male patients, 18 years old or older - Histologically proven infiltrating carcinoma of the breast on core needle biopsy that is: estrogen receptor (ER)/progesterone receptor (PR) ≤10% staining by immunohistochemistry (IHC) and HER2 positive - IHC 3+, in situ hybridization (ISH) ≥2.0, or average HER2 copy number ≥6.0 signals per cell or per current American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) or National Comprehensive Cancer Network (NCCN) guidelines. Note: All histological diagnostic material should be reviewed at enrolling institution as required per local standards. - Unresected, untreated breast cancer that meets one of the following clinical stages (see Appendix A): T2, T3, or T4a-c lesion, any N, M0. Note: Patients with inflammatory breast cancer (T4d) are not eligible. Bilateral cancers are permitted with approval of the Protocol Chair. - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix B) - Adequate organ function as follows: 1. Absolute neutrophil count (ANC) ≥ 1,500/mm3 2. Platelet count ≥ 100,000/mm3 3. Hemoglobin ≥ 10 g/dL 4. Creatinine ≤ 1.5 times the upper limit of normal with creatinine clearance ≥ 50 mL/min using the Modified Cockcroft-Gault method 5. Bilirubin (total) ≤ 1.5 times upper limit normal (with exception of Gilberts syndrome) 6. AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 2 times the upper limit of normal - Adequate cardiac function as defined by left ventricular ejection fraction (LVEF) ≥ 50% on echocardiogram or multi-gated acquisition scan (MUGA) - Able and amenable to baseline and follow-up PET/CT imaging and study-specific biopsy procedures. Note: If there are any imaging concerns that the patient may not be suitable for quantitative PET/CT (e.g., a metallic device directly overlies the breast), discussion with the local and central radiologists is required to confirm eligibility for the trial. Also, it is expected that subjects have all PET/CT imaging done on pre-qualified machines for the study; if baseline imaging done on another machine, please contact the Protocol Chair/designee for guidance prior to confirming eligibility. - The patient, if of childbearing potential, is willing to use effective, non-hormonal contraception while on treatment and for at least 6 months following the last dose of therapy. - Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form. Exclusion Criteria: - Received prior or ongoing local (e.g radiation) or systemic treatment (chemotherapy or endocrine therapy) for the current breast cancer. Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy. - Systemic treatment for prior cancer within the last 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. - Women who are pregnant or nursing - Current use of any investigational agents - Known hypersensitivity to trastuzumab or pertuzumab - Any medical condition that in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy. Specifically, uncontrolled hypertension (systolic >150 and/or diastolic >100), unstable angina, congestive heart failure of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment. | |
| 28 | NCT01940146 | completed | 0.6908711791038513 | phase 2 | ['seasonal allergic rhinitis'] | ["['J30.2']"] | ['sparc placebo', 'sparc1310 i', 'sparc1310 ii', 'sparc1310 iii'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Male or female participants aged 18 to 65 years with history of seasonal allergic rhinitis - Participants able to understand and willing to sign the informed consent form Exclusion Criteria: - Anotomical deviations of the nasal septum that significantly impair ventilation or airflow - Pregnant or nursing women - Positive serology for infectious disease (Hepatitis B or C, HIV) at screening - Parallel participation in another current investigational study, participation in a study within less than 30 days prior to study entry, or previous participation in this same study. | |
| 29 | NCT01943630 | unknown status | 0.7197418212890625 | phase 2 | ['external genital warts'] | ["['B88.3', 'S30.845S', 'S30.846S', 'S30.845A', 'S30.845D', 'S30.846A', 'S30.846D']"] | ['15% as101 gel', 'vehicle'] | ['CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: 1. Women at least 18 years of age and in good health; 2. Must sign an ethics committee approved informed consent form and be able to adhere to study visits and protocol requirements; 3. Women must agree to avoid sexual contact while the gel is on their skin; 4. All study participants who are sexually active must use a protection method of contraception during treatment and for 60 days after completion of treatment; 5. Patients with clinical diagnosis of external genital warts, in the external genitalia including vulva (labia minora and majora), inguinal folds, pubic area, perineum, perianal, or buttocks areas; two or more distinct external genital warts, and wart area to be treated that is equal to or less than 10 cm2. Exclusion criteria: 1. Participation in an investigational trial within 30 days prior to screening; 2. Previous participation in a trial investigating AS101 for any indication; 3. Topical treatment for genital warts within 14 days of screening; 4. Cutaneous surgery, including cryosurgery or laser, to genital area within 30 days of screening; 5. Skin irritations of other clinical signs or symptoms associated with prior therapy. 6. Topical and systemic immunosuppressive or immunomodulatory medications (including corticosteroids) within 30 days prior to screening, and while on study; 7. Current active infection with herpes genitalis or history of herpes genitalis infection within the last 30 days prior to screening (patients on long-term suppressive antiviral therapy are eligible); 8. Diagnosis of high-grade cervical dysplasia; 9. Internal anogenital, vaginal, cervical warts or urethral meatal warts requiring treatment; 10. Chronic or acute skin condition that might interfere with the treatment or evaluation of study drug effect; 11. Screening laboratory tests results from a complete blood count (CBC), chemistry panel and urine pregnancy test obtained during screening: 1. Must be within the site laboratory's defined normal reference ranges, and/or according to the Investigator's decision; 2. Urine pregnancy test in females of childbearing potential must be negative; 3. Inadequate renal function: Serum Creatinine >2.0mg/dL (>2.0 ULN); 4. Inadequate liver function: Serum (total) Bilirubin >2 mg/dl or ALT and/or AST greater than two times the upper limit of the reference range. 12. Uncontrolled infection or acute severe febrile illness; 13. Diagnosed as having uncontrolled cardiovascular, hematological, hepatic, neurological, renal, endocrine, vascular, autoimmune, or gastrointestinal abnormalities or disease; 14. Pregnant or lactating; 15. Known allergy to AS101 or any component of the investigational formulation; or 16. Subjects with any other clinically significant medical condition, psychiatric condition or laboratory abnormality which would, in the judgment of the Investigator, interfere with the subject's ability to participate and comply with the trial. | |
| 30 | NCT01945866 | completed | 0.70634526014328 | phase 2 | ['diabetic macular edema'] | ["['E10.311', 'E10.319', 'E11.311', 'E11.319', 'E13.311', 'E13.319', 'E10.3513']"] | ['intravitreal ranibizumab 0.3 mg', 'dexamethasone intravitreal implant'] | ['CN\\C(NCCSCC1=CC=C(CN(C)C)O1)=C/[N+]([O-])=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: 1. Age ≥ 18 years i) Individuals <18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable. 2. Diagnosis of diabetes mellitus (type 1 or type 2) 3. Any one of the following will be considered to be sufficient evidence that diabetes is present: 1. Current regular use of insulin for the treatment of diabetes 2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes 3. Documented diabetes by ADA (American Diabetes Association) and/or WHO (World Health Organization) criteria 4. At least one eye meets the study eye criteria listed below. 5. Fellow eye (if not a study eye) meets criteria. 6. Able and willing to provide informed consent. Meets all of the following ocular criteria in at least the one eye: 1. At least 3 injections of anti-VEGF drug (ranibizumab, bevacizumab, or aflibercept) within the prior 20 weeks. 2. Visual acuity letter score in study eye ≤ 78 and ≥24 (approximate Snellen equivalent 20/32 to 20/320). 3. On clinical exam, definite retinal thickening due to DME involving the center of the macula. 4. OCT CSF thickness, within 8 days of enrollment: i) On Zeiss Cirrus ≥ 290 microns in women; ≥ 305 in men ii) On Heidelberg Spectralis: ≥ 305 microns in women; ≥ 320 in men 5. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs. Exclusion Criteria: An individual is not eligible if any of the following exclusion criteria are present: 1. History of chronic renal failure requiring dialysis or kidney transplant. 2. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control). 3. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months. 4. Participation in an investigational trial within 30 days of enrollment that involved treatment with any drug that has not received regulatory approval for the indication being studied. Note: study participants cannot receive another investigational drug while participating in the study. 5. Known allergy to any component of the study drugs (including povidone iodine prep). 6. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the individual can become eligible. 7. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month prior to enrollment. 8. Systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment or anticipated use during the study. These drugs cannot be used during the study. 9. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 9 months. Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed. 10. Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next 9 months. The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye unless otherwise specified): 1. Macular edema is considered to be due to a cause other than DME. An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are the primary cause of the macular edema. 2. An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal condition, etc.). 3. An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.). 4. Substantial posterior capsule opacity that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., opacity would be reducing acuity to 20/40 or worse if eye was otherwise normal). 5. History of intravitreal anti-VEGF drug within 21 days prior to enrollment. 6. History of intravitreal or peribulbar corticosteroids within 3 months prior to enrollment. 7. History of macular laser photocoagulation within 4 months prior to enrollment. 8. History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the 6 months following enrollment into run-in phase. 9. Any history of vitrectomy. | |
| 31 | NCT01949116 | completed | 0.45844462513923645 | phase 2 | ['hiv infections'] | ["['Z21']"] | ['ldmtx', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | 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. - Had to be on continuous ART for greater than or equal to 24 weeks prior to study entry. This was defined as continuous active therapy for the 24-week period prior to study entry with no treatment interruption longer than 7 consecutive days and a total duration off treatment of no more than 14 days in the 90 days prior to study entry. - CD4 T-cell count greater than or equal to 400 cells/mm^3 obtained within 60 days prior to study entry by any U.S. laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent - HIV-1 RNA level below the limit of quantification using a FDA-approved assay for at least 24 weeks prior to study entry and confirmed within 60 days prior to study entry. The assay used for eligibility could be performed by any U.S. laboratory that had a CLIA certification or its equivalent. NOTE: Single determinations that are between the assay quantification limit and 200 copies/mL were allowed as long as the preceding and subsequent determinations are below the level of quantification. - The following laboratory values obtained within 60 days prior to study entry by any U.S. laboratory that has a CLIA certification or its equivalent: 1. Fasting glucose less than 180 mg/dL 2. Alanine aminotransferase (ALT) [serum glutamic pyruvic transaminase (SGPT)] less than 2 times the upper limit of normal (ULN) 3. Aspartate aminotransferase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] less than 2 times the ULN 4. Estimated creatinine clearance (CrCl) greater than or equal to 50 mL/min by Cockcroft-Gault. NOTE: Candidates who were taking tenofovir disoproxil fumarate (TDF) as part of their ART regimen should have an estimated CrCl greater than or equal to 60 mL/min. 5. White blood cell (WBC) greater than 3,000/mm^3 6. Hemoglobin greater than 12.0 g/dL 7. Platelets greater than 150,000/mm^3 - Female candidates who were postmenopausal (i.e., of non-childbearing potential) were defined as having either: 1. Appropriate medical documentation of prior hysterectomy and/or complete bilateral oophorectomy (i.e., surgical removal of the ovaries, resulting in "surgical menopause" and occurring at the age at which the procedure was performed), OR 2. Permanent cessation of previously occurring menses as a result of ovarian failure with documentation of hormonal deficiency by a certified healthcare provider (i.e., "spontaneous menopause"). - Male candidates must agree not to participate in a conception process (i.e., active attempt to impregnate, sperm donation). If participating in sexual activity that could lead to pregnancy, the male participant must agree to the use of TWO reliable forms of contraceptives simultaneously while on study and for a minimum of 3 months after therapy. - Candidates who were not of reproductive potential (defined as women who have been postmenopausal for at least 24 consecutive months or men who have documented vasectomy) were eligible for the study without requiring the use of contraceptives. - Moderate or high CVD risk defined as: A) Documented CVD as assessed by meeting at least 1 of 3 criteria below: 1. Coronary artery disease (CAD): prior myocardial infarction (MI) due to atherosclerosis, coronary artery bypass graft surgery, percutaneous coronary intervention, or angiographic CAD with luminal diameter stenosis of at least one coronary artery at least 50%. 2. Cerebrovascular disease: prior ischemic stroke of carotid origin, carotid endarterectomy or stenting, or angiographic carotid stenosis of at least 50%. 3. Peripheral arterial disease: prior lower extremity arterial surgical or percutaneous revascularization procedure, or angiographic lower extremity arterial stenosis of at least 50%. OR B) Controlled type II diabetes mellitus (HbA1C less than or equal to 8.0% within the past 90 days prior to study entry, regardless of use of medications) OR C) Any one of the following CVD risk factors below: 1. Current smoking: self-report of smoking at least a half a pack of cigarettes a day, on average, in the past month. 2. Hypertension (HTN): two consecutive blood pressure (BP) readings with either systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg; or on antihypertensive medications. 3. Dyslipidemia: defined as non-high-density lipoprotein (HDL)-C greater than 160 mg/dL or HDL-C less than or equal to 40 mg/dL, regardless of medication use. 4. High-sensitivity C-reactive protein (hsCRP) greater than or equal to 2 mg/L at screening Ability and willingness of candidate to provide informed consent - Completion of the Flow-mediated Vasodilation (FMD) assessments. NOTE: The FMD must be performed at the site and confirmed as acceptable by the University of Wisconsin Atherosclerosis Imaging Research Program (UW AIRP) core lab prior to study entry. If the FMD is deemed unacceptable, a repeat scan must be performed prior to enrollment. - Appropriate documentation from medical records of prior receipt of pneumococcal vaccination (with both the 13-valent conjugant vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPV23]) within the last 5 years. If no documentation is available, then the PCV13 and PPV23 series (PCV13 vaccine followed by PPV23 vaccine at least 8 weeks later) should be completed more than 14 days prior to study entry. Exclusion Criteria: - Acute or serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry. NOTE: Treatment should have ended at least 60 days prior to study entry for eligibility. - Documentation of any CDC category C AIDS-indicator condition or oropharyngeal candidiasis (thrush) within 90 days prior to study entry - Receipt of antibiotic therapy within 30 days prior to study entry - Latent tuberculosis (TB) infection (defined as a positive purified protein derivative [PPD] greater than or equal to 5 mm, positive interferon-gamma release assay, or positive T-spot test at any time in the past) or evidence of latent TB on the screening chest x-ray that had not been completely treated or was treated within the past 6 months prior to study entry - TB disease that required treatment within 48 weeks prior to study entry - Life-threatening fungal infection requiring treatment, in the opinion of the site investigator, within 48 weeks prior to study entry - Herpes-zoster viral infection that required treatment within 90 days prior to study entry - A history of or current, active hepatitis B infection defined as positive hepatitis B surface antigen (HBsAg) test or positive hepatitis B virus (HBV) DNA in candidates with isolated hepatitis B core antibody (HBcAb) positivity, defined as negative HBsAg, negative hepatitis B surface antibody (HBsAb), and positive HBcAb within 24 weeks prior to study entry. NOTE: Candidates who were positive for hepatitis B surface antigen but who were HBV DNA negative were permitted in the study. - Chronic hepatitis C infection defined as a positive hepatitis C antibody and positive hepatitis C RNA at any time prior to study entry. NOTE: Candidates who were positive for hepatitis C antibody but whowerehepatitis C virus (HCV) RNA negative are permitted in the study. Candidates who had been treated for hepatitis C should be HCV RNA negative for at least 24 weeks after completion of therapy to be eligible for the study. - Previously diagnosed myelodysplasia syndrome - Treated lymphoproliferative disease less than or equal to 5 years prior to study entry - Clinically significant lung disease on the screening chest x-ray that, in the opinion of the site investigator, places the candidate at increased risk of lung toxicity (e.g., history of pulmonary fibrosis, interstitial lung disease, or pulmonary lymphoproliferative disease) - Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry - Change in the ART regimen in the 12 weeks prior to study entry or intended modification of ART during the study. NOTE: Modifications of ART doses during the 12 weeks prior to study entry were permitted. In addition, the change in formulation (e.g., from standard formulation to fixed-dose combination) was allowed within 12 weeks prior to study entry. A within class single drug substitution (e.g., switch from nevirapine to efavirenz or from atazanavir to darunavir) is allowed within 12 weeks prior to study entry, with the exception of a switch from any other nucleoside reverse transcriptase inhibitor (NRTI) to abacavir. No other changes in ART in the 12 weeks prior to study entry were permitted. - Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation - Average daily consumption of three or more alcoholic beverages for 4 weeks prior to study entry or intention to consume an average of two or more alcoholic beverages a day during the study. NOTE: An alcohol-containing beverage is defined as 12 ounces of beer, 4 ounces of wine, or 1 ounce of spirits. - Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements - Changes in lipid-lowering or antihypertensive medication within 90 days prior to study entry or expected need to modify these medications during the study. NOTE: Lipid-lowering medication includes: statins, fibrates, niacin (dose greater than or equal to 250 mg daily), and fish-oil/omega 3 fatty acids (dose greater than 1000 mg of marine oils daily). - Vaccination (e.g., influenza, pneumococcal polysaccharide) within 14 days prior to study entry - Anticipated need to receive vaccination (e.g., influenza, pneumococcal polysaccharide) within 1 week prior to Week 4, 12, 24, or 36 study visits - Excess extracompartmental fluids including ascites, pericardial fluid, and pleural effusions which, in the opinion of the study investigators, would result in difficulty in monitoring the dose of MTX - Use of drugs that alter folic acid metabolism such as trimethoprim/sulfamethoxazole or reduce tubular excretion such as probenecid within 14 days prior to study entry - New York Heart Association Class IV congestive heart failure - Diabetes mellitus with HbA1C greater than 8.0% within the past 90 days prior to study entry | |
| 32 | NCT01950299 | completed | 0.7179027795791626 | phase 2/phase 3 | ['acute myocardial infarction'] | ["['I21.9', 'I23.8', 'I23.0', 'I24.0', 'I23.1', 'I23.2', 'I23.4']"] | ['anakinra 100 mg', 'anakinra 100 mg', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | INCLUSION CRITERIA: In order to be eligible for this study, patients must meet ALL the 3 Inclusion criteria and NONE of the Exclusion criteria. 1. Acute STEMI defined as chest pain (or equivalent) with an onset within 12 hours and ECG evidence of ST segment elevation (>1 mm) in 2 or more anatomically contiguous leads that is new or presumably new 2. Planned or completed coronary angiogram for potential intervention 3. Age>21 EXCLUSION CRITERIA: - Inability to give informed consent - Pregnancy - Preexisting congestive heart failure (American Heart Association/American College of Cardiology class C-D, New York Heart Association III-IV) - Preexisting severe left ventricular dysfunction (EF<20%) - Preexisting severe valvular heart disease - Active infections (acute or chronic) - excluding Hepatitis C Virus (HCV)+ with undetectable RNA - Recent (<14 days) or active use of anti-inflammatory drugs (not including non-steroidal anti-inflammatory drugs [NSAIDs] or corticosteroids used for IV dye allergy only) - Chronic inflammatory disease (including but not limited to rheumatoid arthritis, systemic lupus erythematosus) - Active malignancy - excluding carcinoma in situ [any organ] and non-melanoma skin cancer - Anticipated need for cardiac surgery - Neutropenia (absolute neutrophil count<1,800/mm3) | |
| 33 | NCT01953406 | withdrawn | no participants were enrolled. therefore, we stop this study, prematurely. | 0.2984641194343567 | phase 2 | ['hepatocellular carcinoma', 'lung metastasis'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['5-fluorouracil', 'mitomycin'] | ['FC1=CNC(=O)NC1=O', 'CO[C@]12[C@H]3N[C@H]3CN1C1=C([C@H]2COC(N)=O)C(=O)C(N)=C(C)C1=O'] | Inclusion Criteria: - Patients who have received previous local therapy treatments for the intrahepatic hepatocellular carcinoma (RFA, PEI, cryoablation, surgery, resection) and who don't have any viable intrahepatic tumor within 3 months of imaging (dynamic liver CT or liver MRI) after the locoregional therapy - Patients who have measurable lung metastasis - Patients who have received their last dose of sorafenib more than 14 days before and who had progressive disease of lung metastasis with sorafenib - Patients who have risk factors of hepatocellular carcinoma (chronic hepatitis B, chronic hepatitis C, liver cirrhosis) - Age : 18 years to 80 years - ECOG Performance Status of 0 to 2 - Child-Pugh class A,B (Child-Pugh score 5-9) - Adequate bone marrow, liver function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening: - WBC count > 1,000/mm3 - Absolute neutrophil count > 500/mm3 - Hb > 7.0 g/dL - Platelet count > 50,000 /mm3 - Bilirubin < 3 mg/dL - Adequate clotting function: INR < 2.3 or < 6sec Exclusion Criteria: - Child-Pugh score > 10 - ECOG Performance Status > 3 - History of organ allograft - Patients with uncontrolled co-morbidity which needs treatment - Patients who have received prior systemic chemotherapy except sorafenib |
| 34 | NCT01955707 | completed | 0.3584425449371338 | phase 2 | ['acute ischemic stroke'] | ["['I25.5', 'H47.013', 'H93.013', 'G45.9', 'H47.011', 'H47.012', 'H47.019']"] | ['natalizumab', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Key Inclusion Criteria: - Diagnosis of acute ischemic stroke. - Score of ≥6 points on the National Institute of Health Stroke Scale (NIHSS) at Screening. - At least 1 acute infarct with largest diameter of more than 2 cm on Baseline brain diffusion-weighted imaging (DWI). - Participants who have received reperfusion therapy may be eligible to participate but must meet all eligibility criteria and perform the Baseline study magnetic resonance imaging (MRI) after reperfusion therapy has been completed. - Subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for at least 3 months after their dose of study treatment. Key Exclusion Criteria: - Presence of any intracranial hemorrhage (ICH) on head computed tomography (CT) or non-petechial ICH on screening MRI. - Stroke isolated to the brainstem. - Presence of coma - Expected to die OR unable to be evaluated within 5 days. - Hypotension requiring the use of intravenous (IV) vasopressor support or systolic blood pressure <90 mmHg at the time of randomization. - Known prior treatment with natalizumab. - Immunocompromised subjects, as determined by the Investigator. - History of progressive multifocal leukoencephalopathy (PML). - Contraindications to MRI, e.g., implanted pacemaker or other contraindicated implanted metal devices, history of or risk for side effects from gadolinium, or claustrophobia that cannot be medically managed. NOTE: Other protocol-defined inclusion/exclusion criteria may apply. | |
| 35 | NCT01962896 | terminated | low accrual | 0.2529406249523163 | phase 2 | ['relapsed / recurrent germ cell tumors'] | ["['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']"] | ['erlotinib', 'sirolimus'] | ['COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2', 'CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2'] | Inclusion Criteria: - Patients must be greater than 12 months and less than 50 years of age at the time of study enrollment. - Patients must have had histologic verification of an extracranial germ cell tumor that is not a pure mature teratoma. - Patients must have sufficient tumor tissue available to allow assessment of EGFR and mTOR pathway activation (see Section 5.2.3 for sample requirements) - Patients must have relapsed or refractory disease following at least two prior cisplatin containing chemotherapy regimens. - Patients must have measurable disease, documented according to RECIST criteria, or evaluable disease with a standard tumor marker (AFP and/or HCG) greater than 10 times the upper limit of normal. - Patients must have a Lansky or Karnofsky performance status score of ≥ 50. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. - Patients must have a life expectancy of greater than 8 weeks. - Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy. - Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment. - Patients must be > 7 days since treatment with hematopoetic growth factors (>14 days for Neulasta). - Patients must be >7 days since therapy with a biologic agent and beyond the period for which adverse events of the biologic agent are known to occur if longer. - Patients must be >3 half-lives since therapy with a monoclonal antibody. - Patients must be >42 days since completion of any immunotherapy (i.e. tumor vaccines). - Patients must be greater than 2 weeks since most recent palliative XRT and greater than 6 weeks since substantial bone marrow irradiation. - Patients must be greater than 8 weeks since prior stem cell transplant or infusion and without evidence of active graft vs. host disease. - Adequate bone marrow function defined as: - Peripheral absolute neutrophil count (ANC) of at least 1,000/ L - Platelet count of at least 100,000/ L (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment) - Hemoglobin 8.0 g/dL (may receive RBC transfusions). - Adequate renal function defined as: - Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or - Maximum serum creatinine (mg/dL) based on age/gender - Adequate liver function defined as: - Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age - SGPT (ALT) ≤ 2.5 x ULN (for the purpose of this study, the ULN for SGPT is 45 U/L) - Serum albumin ≥ 2 g/dL. - Adequate central nervous system function defined as: o Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled. - Serum cholesterol levels must be less than Grade 2 (< 300 mg/dL), and serum triglyceride levels must be less than Grade 2 (< 2.5 x ULN). Exclusion Criteria: - Patients with active brain metastases are not eligible as lethal intratumoral hemorrhages have been reported with erlotinib therapy. Patients with brain metastases that have been treated and stable for > 30 days following treatment will be eligible. - Patients who are pregnant or breast feeding will not be entered into the study as erlotinib is teratogenic. Pregnancy tests must be obtained in females who are post-menarchal. Post-menarchal females with HCG secreting tumors will be excluded as pregnancy can't be excluded. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of the study. - Concomitant medications - Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. - Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible. - Anticonvulsants: Patients who are receiving enzyme-inducing anticonvulsants are not eligible (see Appendix 1 for a list of enzyme- inducing anticonvulsants). - Anticoagulants: Use of warfarin is not allowed while on study. Patients already on warfarin should use alternative anticoagulants while on this study. Warfarin must not have been administered within 7 days of enrollment. - Smoking: Smoking induces CYP3A4/5 enzymes and decreases exposure to sirolimus and erlotinib. Thus, patients must not smoke for 10 days prior to enrollment and for the duration of therapy. - Infection: Patients who have an uncontrolled infection are not eligible. - Drug interactions: Sirolimus and erlotinib are primarily metabolized by the CYP3A4/5 enzymes. Drug exposure is substantially effected by CYP inhibitors (increased exposure) and inducers (decreased exposure). Thus, concomitant administration of strong CYP3A4/5 inhibitors or inducers is prohibited while on therapy. See Appendix 1 for a list of these medications. Patients must not have received these medications for a minimum of 10 days prior to enrollment. - Patients who have received prior therapy targeting EGFR with small molecule tyrosine kinase inhibitors or monoclonal antibodies are NOT eligible. - Prior treatment with mTOR or TORC1/2 inhibitors (eg, rapamycin, temsirolimus, everolimus, sirolimus) is NOT allowed. - Patients who have had major surgery within 3 weeks prior to enrollment are not eligible. Procedures such as placement of a central vascular catheter, or limited tumor biopsy, are not considered major surgery. - Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. |
| 36 | NCT01966731 | active, not recruiting | 0.4406208395957947 | 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 | |
| 37 | NCT01972217 | active, not recruiting | 0.4273952543735504 | phase 2 | ['metastatic castration-resistant prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['olaparib', 'placebo', 'abiraterone', 'prednisone or prednisolone'] | ['OC1=NN=C(CC2=CC(C(=O)N3CCN(CC3)C(=O)C3CC3)=C(F)C=C2)C2=CC=CC=C12', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C', '[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)C=C[C@]12C'] | Inclusion Criteria: 1. Provision of signed and dated written informed consent prior to any study specific procedures. 2. Male aged 18 years and older. 3. Histologically or cytologically proven diagnosis of prostate cancer. 4. Candidate for abiraterone therapy with documented evidence of metastatic castration-resistant prostate cancer. Metastatic status is defined as at least one documented metastatic lesion on either bone scan or CT/MRI scan. Castration resistant prostate cancer is defined as rising PSA or other signs of disease progression despite treatment with androgen deprivation therapy and the presence of a castrate level of testosterone (≤50 ng/dL). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 with no deterioration over the previous 2 weeks. 6. Patients must have a life expectancy ≥12 weeks. 7. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations, and completing PRO instruments. 8. Patients must be on a stable concomitant medication regimen, defined as no changes in medication or in dose within 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing. 9. For the randomised phase only, patients must have received chemotherapy in the form of docetaxel treatment for metastatic castration-resistant prostate cancer. Note: patients who discontinued docetaxel for toxicity reasons and without completing the full course will still be eligible to enter this study provided they received at least 2 cycles of chemotherapy. Provide informed consent for the pharmacogenetic sampling and analyses. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff, its agents and/or staff at the study site). 2. Previous treatment in the present study. 3. Treatment with any of the following: - Previous exposure to any 2nd generation anti-hormonal including abiraterone and enzalutamide - More than 2 prior courses of chemotherapy for metastatic prostate cancer - Previous use of immunotherapy or radium-223 for the treatment of metastatic prostate cancer - Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment; - Any previous exposure to a CYP17 (17α-hydroxylase/C17,20-lyase) inhibitor; - Substrates of CYP2D6 with a narrow therapeutic index (eg, thioridazine); - Potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort). - Any previous treatment with a PARP inhibitor, including olaparib. 4. With the exception of alopecia or toxicities related to the use of gonadotropinreleasing hormone agonists, any unresolved toxicities from prior therapy greater than CTCAE Grade 2 at the time of starting study treatment. 5. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment. 6. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 7. Any of the following cardiac criteria: - Mean resting QTc >470 msec obtained from 3 ECGs - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval. 8. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years. 9. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: - Absolute neutrophil count (ANC) <1.5 x 109/L - Platelet count <100 x 109/L - Haemoglobin (Hb) <100 g/L - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x upper limit of normal (ULN) if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases - Total bilirubin >1.5 x ULN if no liver metastases or >3 x ULN in the presence of liver metastases (except in the case of Gilbert's disease) - Creatinine >1.5 x ULN concurrent with creatinine clearance <50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is >1.5 x ULN - If bone metastases are present and liver function is otherwise considered adequate by the Investigator then elevated alkaline phosphatase (ALP) will not exclude the patient. 10. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of olaparib or abiraterone. 11. History of hypersensitivity to active or inactive excipients of olaparib or abiraterone or drugs with a similar chemical structure or class to olaparib or abiraterone. 12. Patients with myelodysplastic syndrome/acute myeloid leukaemia. 13. Current disease or condition known to interfere with absorption, distribution, metabolism, or excretion of drugs, at the Investigator's discretion. 14. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 15. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements. Exclusion from the genetic research may be for any of the exclusion criteria specified in the main study or any of the following: 16. Previous allogeneic bone marrow transplant. 17. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the pharmacogenetic sample collection. | |
| 38 | NCT01972347 | active, not recruiting | 0.33331024646759033 | phase 2 | ['melanoma'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['dabrafenib', 'trametinib'] | ['CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1', 'CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1'] | Inclusion Criteria: - Age ≥18 years - Histologically confirmed AJCC Stage IIIB or IIIC (Tx, T1-4, N1b, N2b, N2c, N3, Mo) cutaneous melanoma or unknown primary determined to be BRAF V600 mutation positive, with sufficient nodal or in-transit disease to enable biopsies prior to surgery.Patients must have disease that is measurable per RECIST version 1.1 - Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 - Adequate baseline organ function - Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 4 months after the last dose of study treatment - Men with any female partner of childbearing potential must agree to use effective contraception from 14 days prior to commencing study treatment, throughout the treatment period and for 4 months after the last dose of study treatment Exclusion Criteria: - Known mucosal or ocular melanoma or any unresectable in-transit metastases - Evidence of distant metastatic disease on screening evaluation - Prior anti-cancer treatment for melanoma (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, investigational treatment or radiotherapy). Prior surgery for melanoma is allowed. - Taken an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to commencing study treatment. - Current or expected use of a prohibited medication(s) - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO) - Known HIV - A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency - History of another malignancy or a concurrent malignancy except: 1. Patients who have been disease-free for 3 years and have a life expectancy of > 5 years; 2. Patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas. - A history or evidence of cardiovascular risk including any of the following: a. QT interval corrected for heart rate using the Bazett's formula ≥480 msec or ≥ 450 msec for patients with bundle branch block; b. History or evidence of current clinically significant uncontrolled arrhythmias; c. History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to commencement of study treatment; d. History or evidence of current ≥ Class II congestive heart failure; e. Abnormal cardiac valve morphology documented by echocardiogram which in the opinion of the investigator could interfere with the patient's safety. f. Treatment refractory hypertension defined as a blood pressure of systolic > 140 mm Hg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy. - A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) - Any serious or unstable pre-existing medical conditions (aside from the malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the treating clinician, could interfere with the patient's safety, obtaining informed consent, or compliance with study procedures. - Breastfeeding females | |
| 39 | NCT01975662 | terminated | slow accrual of participants | 0.7077012658119202 | phase 2 | ['bacteremia due to staphylococcus aureus'] | ["['A41.2', 'J15.20', 'J15.29', 'P23.2', 'A41.1', 'A41.01', 'A41.02']"] | ['daptomycin', 'vancomycin'] | ['CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=C(N)C=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O', 'CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=C(N)C=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O'] | Inclusion Criteria: - Age > 21 years. - Inpatient at the time of enrolment. - MRSA bacteremia due to MRSA isolates with a vancomycin MIC > 1.5 ug/ml. - Be prepared to undergo all treatments and procedures, and attend follow-ups as per the trial protocol. Exclusion Criteria: - Allergy to any of the study medications. - Pregnant or breastfeeding females. - Unable to provide consent or have no legally authorized representatives. - Currently enrolled or within the past three months participated in an interventional antibiotic or vaccine trial. - >48 hours after MRSA vancomycin MIC > or equal to1.5 ug/ml confirmation by the microbiology laboratory (assessed from time of lab report). - Patients on palliative care or with less than 24 hours of life expectancy (as discussed with their primary physicians). - Polymicrobial bacteremia [see (a) below]. - Pneumonia [see (b) below]. - On treatment with linezolid, tigecycline or ceftaroline immediately prior to enrolment. - Previous blood cultures positive for MRSA in the preceding one month. - On vancomycin or daptomycin treatment for more than 96 hours prior to enrolment. - BSI due to MRSA with vancomycin MIC > or equal to 4 ug/ml. - Baseline serum creatine kinase more than 1.5 times the upper limit of normal. - Patients with prosthetic heart valves - Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial. 1. .Isolation of a significant organism other than MRSA from index blood cultures or blood cultures taken up to two weeks prior to enrolment and/or for which the patient is still on treatment. 2. .Chest x-ray at baseline consistent with pneumonia AND at least 2 of the following signs and symptoms: New onset or worsening cough, purulent sputum or increased suctioning requirements, dyspnea/tachypnea or respiratory rate > 30/min, hypoxemia or worsening gas exchange as determined by study investigator.) |
| 40 | NCT01975935 | completed | 0.5595738887786865 | phase 2 | ['diabetes mellitus type 2', 'non-alcoholic fatty liver disease', 'obesity'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']", "['Z52.6', 'K71.8', 'K71.7', 'A06.4', 'C22.0', 'C22.3', 'K70.0']", "['E66.8', 'E66.9', 'E66.1', 'O99.214', 'O99.215', 'O99.210', 'O99.211']"] | ['amlexanox', 'placebo'] | ['CC(C)C1=CC2=C(OC3=NC(N)=C(C=C3C2=O)C(O)=O)C=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - ≥ 18 years old at baseline. - Is male, female not of childbearing potential, or meets all the following criteria if female of childbearing potential (including perimenopausal women who have had a menstrual period within one year): - Not breastfeeding. - Negative pregnancy test result (human chorionic gonadotropin, beta subunit [βhCG]) at baseline (not applicable to hysterectomized females). - Must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate when use consistently and correctly, such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire duration of study period. - Has physician-confirmed diabetes mellitus with a clear diagnosis or per ADA criteria with fasting glucose>126 mg/dL or HbA1c >6.4% or 2 hour GTT >200 mg/dL. - BMI ≥27 and <45 kg/m2. - On no medications or only on first line oral medications (such as Metformin and/or DPP IV inhibitors) for treatment of Type 2 diabetes mellitus with a stable regimen for >12 weeks. - Alcohol consumption of less than 40 grams/week. - A liver US confirming presence of fatty infiltration of the liver. - Is able to read, understand and sign the U of M IRBMED approved informed consent form (ICF), communicate with study physician and study team, understand and comply with protocol requirements. Exclusion Criteria: - On insulin, or other injectables for treatment of Type 2 diabetes. - Unable to conduct home based glucose monitoring. - HbA1c <6.5% and >10.0% (set to achieve uniformity in the study population). - Presence of advanced liver disease (as evidenced by abnormal synthetic function, abnormal PT or albumin). - Evidence of other etiologies of viral hepatitis. - Presence of hematologic, bone marrow and/or other abnormalities. - Presence of hemoglobinopathy or other hematological abnormalities that will interfere with accurate measurement of HbA1c. - Presence of HIV infection. - Inability to give informed consent. - Presence of ESRD, any type of active cancer, or >class 2 congestive heart failure ((New York Heart Association Functional Classification System), based on medical history and physical examination. - Active chronic infection such as known chronic osteomyelitis or tb, etc. (may be transient). - Creatinine >1.5 mg/dL. - Proliferative diabetic retinopathy, nonproliferative retinopathy is allowed. - Unable to ambulate. - Clinically relevant CAD: history of stent, CABG or cardiologist confirmed angina. - Any other condition in the opinion of the investigators that may impede successful data collection. | |
| 41 | NCT01977820 | terminated | recruitment challenges | 0.45524314045906067 | phase 2 | ['phenylketonuria'] | ["['E70.0']"] | ['sapropterin', 'placebo'] | ['[H][C@@]1(CNC2=C(N1)C(=O)NC(N)=N2)[C@@H](O)[C@H](C)O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Written informed consent given before any trial-related activities are carried out - Women or men with documented PKU diagnosed by at least two phenylalanine levels equal or greater than 600 micromole per liter (mcmol/L) - For women of childbearing potential: a negative urine pregnancy test is required at screening and willingness to use a highly effective method of contraception is required during the study and follow-up periods - Aged greater than or equal to (>=) 18 to 29 years, inclusive - Mean blood phenylalanine levels 600 to 1000 mcmol/L during 12 months preceding inclusion in the study. The mean should be calculated from at least 3 blood phenylalanine values over the last 12 months. Screening blood phenylalanine level can be one of these values. There should be at least one value dated between Month -12 and -6 before Screening and at least one value dated between Month -6 and Screening - An intelligence quotient (IQ) score greater than or equal to 85, assessed a maximum of 2 years before screening with an age-appropriate Wechsler scale. If no IQ test result is available, IQ testing must be performed as part of Screening using an age-appropriate Wechsler scale before the subject can be included - Subjects willing to comply with all study procedures, including willingness to continue current dietary recommendations during the whole trial duration Exclusion Criteria: - Subjects with tetrahydrobiopterin (BH4) deficiency - Previous exposure to sapropterin or BH4 for greater than 30 days (or exposure to sapropterin or BH4 for less than or equal to 30 days but within the previous 6 months prior to Screening visit) - Subjects who, according to the Investigator, will not be able to comply with study procedures and computerized neuropsychological testing - Any significant illness which, according to the Investigator, might preclude participation in the study (including neurological disease, cardio-vascular disease, history of seizure, predisposition to convulsions, renal or hepatic insufficiency, and active malignancy) - Any significant illness, medication or substance abuse which, according to the Investigator, might affect cognitive function and cognitive testing (for example, significant visual or motor impairment, history of major head trauma, history of stroke, alcoholism, drug dependency, psychological disorder requiring chronic use of psychotropic medications such as anxiolytics, antidepressants, antipsychotic medication, mood stabilizers, and hypnotics) - Concomitant forbidden medication as described in the Kuvan® Summary of Product Characteristics, namely, inhibitors of dihydrofolate reductase (for example, methotrexate, trimethoprim), medications that are known to affect nitric oxide synthesis (for example, glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, molsidomin, phosphodiesterase type 5 inhibitors, and minoxidil), and levodopa, as it may cause increased excitability and irritability - Known hypersensitivity to sapropterin or any ingredients in the product's formulation, or to other approved or non-approved formulations of BH4 - Subjects who have undergone cognitive neuropsychological testing similar to that to be performed as part of this trial with the following time limits: tasks with limited practice effect performed in the last 6 months, and tasks with important practice effect (such as tasks involving development of strategies) performed in the year preceding inclusion in the trial. Whether a task falls into one or the other category is left to Investigator judgment - Female subjects who are pregnant or in the lactation period - Subjects currently participating to another clinical trial or who participated in a previous clinical trial within 30 days prior to screening - Legal incapacity or limited legal capacity |
| 42 | NCT01978236 | terminated | this study was terminated due to the limited enrollment. | 0.3040768802165985 | phase 2 | ['melanoma and brain metastases'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['dabrafenib 150 mg', 'trametinib 2.0 mg'] | ['CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1', 'CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1'] | Inclusion Criteria: - Signed written informed consent - Histologically-confirmed metastatic melanoma (Stage IV), carrying BRAF V600E or V600K mutation as determined by testing certified for clinical diagnostic purposes. Previously performed certified BRAF testing is acceptable. If no prior BRAF mutation testing results are available, testing of a distant metastasis is preferred, but testing of a regional metastasis or primary tumor is also acceptable - At least one intracranial lesion >=1.0 cm but <=4.0 cm that can be treated with surgical resection in the opinion of the treating physicians, and for which immediate local therapy is not clinically indicated - At least two extracranial lesions that are easily accessible for biopsy, in the judgment of the treating physician. Easily accessible tumors may include cutaneous, subcutaneous, and superficial lymph node metastases. - Age >18 years of age. - Able to swallow and retain oral medication - Women with child-bearing potential must be willing to practice acceptable methods of birth control during the study - Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment. - Must be able to understand and comply with protocol requirements and instructions - Eastern Co-operative Oncology Group (ECOG) performance status of 0-2 - Must have adequate organ function as defined by the following screening values (Retesting of borderline screening organ function and treatment with blood transfusions, growth factors etc. will be allowed): - Absolute neutrophil count (ANC) >=1.2x10^9/L - Hemoglobin >=9 g/dL - Platelets >=100x10^9/L - Serum bilirubin <=1.5 x upper limit of normal (ULN) - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5xULN - Serum creatinine <=1.5 mg/dL (If serum creatinine is >1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault Method Creatinine clearance must be >50 mL/min) - Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) <=1.3xULN - Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal (LLN) Exclusion Criteria: - Neurological symptoms related to brain metastasis that are not controlled with a stable or decreasing dose of oral steroids for at least 7 days prior to starting GSK2118436 - Prior Central Nervous System (CNS)-directed local therapies, including surgical resection, whole brain radiation (WBRT), Stereotactic radiosurgery (SRS), or gamma knife (GK) - Previous treatment with a BRAF or MEK inhibitor - Cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or major surgery) or investigational anti-cancer drugs within the last 3 weeks, or chemotherapy without delayed toxicity within the last 2 weeks, preceding the first dose of study treatment. - Current or expected use of a prohibited medication, including enzyme-inducing antiepileptic drugs (EIAEDs) during treatment with GSK2118436. - Presence of leptomeningeal disease or dural metastases. - History of another active malignancy within the past 5 years, or any malignancy with a confirmed activating RAS mutation. The prospective RAS mutation testing is not required, however, if results of previous RAS testing are known, they must be used in assessing eligibility. Subjects with a history of completely resected non-melanoma skin cancer are eligible. - Known allergies against contrast agents required for magnetic resonance imaging (MRI) of intracranial lesions, or other contraindications for MRI, i.e., pacemaker - Current use of therapeutic warfarin. Low-molecular-weight heparin and prophylactic low-dose warfarin are permitted - Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0) Grade 2 or higher from previous anti-cancer therapy, except alopecia - Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. - History of a prior symptomatic stroke, dementia, or other significant central neurologic condition (i.e. multiple sclerosis) - A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection - Current acute infection requiring intravenous antibiotics - A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency - The history or evidence of following cardiac abnormalities: - Corrected QT (QTc) interval using Bazett's Formula; (QTcB) >= 480 msecs - A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization - Coronary angioplasty or stenting within the past 12 weeks - Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Abnormal cardiac valve morphology (>= Grade 2) documented by echocardiogram (ECHO) - History of or evidence of clinically significant uncontrolled cardiac arrhythmias - Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mm Hg which cannot be controlled by anti-hypertensive therapy - Subjects with intra-cardiac defibrillators or permanent pacemakers - Pregnant, lactating or breastfeeding females - Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures - Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2118436 or excipients that contraindicate their participation |
| 43 | NCT01982292 | completed | 0.5093330144882202 | phase 2 | ['chronic heart failure'] | ["['I50.812', 'I50.22', 'I50.32', 'I50.813', 'I50.23', 'I50.33', 'I50.42']"] | ['rlx030 (serelaxin)', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Key Inclusion Criteria: - Body weight of ≤ 160 kg. - Subjects with compensated CHF (NYHA Class II - III) at time of screening with a prior documented history of chronic heart failure. - NT-proBNP >300 pg/ml (according to central measurement) at visit 1. - Subjects treated with appropriate and guideline-indicated CHF standard of care. - Ability to comply with all requirements, including ability to receive at least a 48 hour infusion plus follow-up time required for each dosing visit. Key Exclusion Criteria: - Current acute decompensated HF - Any major solid organ transplant recipient or planned anticipated organ transplant within 1 year. - Documented history of untreated ventricular arrhythmia with syncopal episodes, ventricular tachycardia, or ventricular fibrillation without ICD (implantable cardioverter defibrillator) with significant hemodynamic consequences within the 3 months prior to screening. - Presence of hemodynamically significant mitral and /or aortic valve disease, except mitral regurgitation secondary to left ventricular dilatation: including significant left ventricular outflow obstruction (e.g., obstructive hypertrophic cardiomyopathy, severe aortic stenosis) - Subjects with severe renal impairment defined as pre-randomization eGFR < 30 ml/min/1.73m2 calculated using the sMDRD equation and/or those receiving current or planned dialysis or ultrafiltration | |
| 44 | NCT01982435 | completed | 0.7207601070404053 | 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 | |
| 45 | NCT01984242 | completed | 0.33614739775657654 | phase 2 | ['renal cell carcinoma'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['atezolizumab (mpdl3280a), an engineered anti-pd-l1 antibody', 'bevacizumab', 'sunitinib'] | ['CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC1=CC=CC=C1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CNC(=O)C1=C(SC2=CC=C3C(NN=C3\\C=C\\C3=CC=CC=N3)=C2)C=CC=C1'] | Inclusion Criteria: - Unresectable advanced or metastatic renal cell carcinoma with component of clear cell histology and/or component of sarcomatoid histology that has not been previously treated with any systemic agents, including treatment in the adjuvant setting - Measurable disease, as defined by RECIST v1.1 - Karnofsky performance score greater than or equal to (>/=) 70 - Adequate hematologic and end-organ function as defined by protocol - Women of childbearing potential and male participants with partners of childbearing potential must agree to use highly effective methods of contraception as defined by protocol Exclusion Criteria: Disease-Specific Exclusions: - Radiotherapy for renal cell carcinoma within 14 days prior to Cycle 1, Day 1 with the exception of single-fraction radiotherapy given for the indication of pain control - Known active malignancies or metastasis of the brain or spinal cord or leptomeningeal disease, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments - Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) - Uncontrolled hypercalcemia or symptomatic hypercalcemia - Malignancies other than renal cell carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death, treated with expected curative outcome General Medical Exclusions: - Life expectancy of less than (<) 12 weeks - Pregnant and lactating women - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan - Participants with active or chronic hepatitis B, active hepatitis C, Human Immunodeficiency Virus (HIV) positive test, significant cardiovascular disease - Prior allogeneic stem cell or solid organ transplant Exclusion Criteria Related to Medications: - Prior treatment with Cluster of Differentiation 137 (CD137) agonists, anti-Cytotoxic T-Lymphocyte Antigen-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents - Treatment with systemic immunostimulatory agents for any reason within 6 weeks or five half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1 - Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1, Day 1 Bevacizumab- and Sunitinib-Specific Exclusions: - Inadequately controlled hypertension - Prior history of hypertensive crisis or hypertensive encephalopathy - New York Heart Association Class II or greater congestive heart failure - History of myocardial infarction or unstable angina, stroke or transient ischemic attack within 3 months prior to Cycle 1, Day 1 | |
| 46 | NCT01986751 | terminated | failure to enroll | 0.5257510542869568 | 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. - |
| 47 | NCT01987453 | completed | 0.734691858291626 | phase 2 | ['hcv infection'] | ["['K94.02', 'K94.12', 'K94.22', 'K94.32', 'N99.511', 'A02.9', 'A31.0']"] | ['ldv/sof', 'rbv'] | ['CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](N2C=CC(=O)NC2=O)[C@](C)(F)[C@@H]1O)OC1=CC=CC=C1', 'NC(=O)C1=NN(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O'] | Key Inclusion Criteria: - Willing and able to provide written informed consent - Infection with HCV genotype 1 - HCV RNA > LLOQ at screening - Participation in a prior Gilead-sponsored study - Screening laboratory values within defined thresholds - Use of two effective contraception methods if female of childbearing potential or sexually active male - Must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator - Must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments Key Exclusion Criteria: - Pregnant or nursing female or male with pregnant female partner - Co-infection with HIV or hepatitis B virus (HBV) - Current or prior history of clinical hepatic decompensation (Groups 1 and 2 only) - Hepatocellular carcinoma (HCC) - History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol Note: Other protocol defined Inclusion/Exclusion criteria may apply. | |
| 48 | NCT01988493 | active, not recruiting | 0.3825090229511261 | 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 | |
| 49 | NCT01991210 | terminated | the primary objective of pfs did not meet pre-specified criteria. | 0.37135979533195496 | phase 2 | ['ovarian cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['dnib0600a', 'pld'] | ['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: - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Histologically documented epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer - Advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed during or within 6 months after the most recent treatment with a platinum-containing chemotherapy regimen and for whom PLD is appropriate therapy - No more than 1 prior cytotoxic chemotherapy regimens for the treatment of PROC and not more than 2 total regimens (defined as any therapy [approved or investigational] with intent to treat the ovarian cancer) - Adequate hematologic, renal and liver function - Willing and able to perform a patient-reported outcome (PRO) survey (including the possibility of using an electronic PRO device) - For women of childbearing potential, agreement to use 1 highly effective form of contraception as defined by protocol through the course of study treatment and for 6 months after the last dose of study treatment Exclusion Criteria: - Primary platinum-refractory disease defined as disease progression during or within 2 months of a first-line, platinum-containing chemotherapy regimen - Anti-tumor therapy, including chemotherapy, biologic, experimental, or hormonal therapy, within 4 weeks prior to Day 1 - Palliative radiation within 2 weeks prior to Day 1 - Prior anthracycline therapy, including prior treatment with PLD (for example, Doxil®, Caelyx®, or Lipodox®) in any setting (for example, in combination with carboplatin or as a single agent) - Prior treatment with NaPi2b or SCL34A2 targeted therapy - Major surgical procedure within 4 weeks prior to Day 1 - Current Grade greater than (>) 1 toxicity (except alopecia and anorexia) from prior therapy or Grade >1 neuropathy from any cause - Left ventricular ejection fraction defined by multigated acquisition (MUGA)/echocardiogram below the institutional lower limit of normal - Evidence of significant, uncontrolled, concomitant disease that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease or significant pulmonary disease - Known active infection, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (within 4 weeks prior to Cycle 1, Day 1) - Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis - Presence of positive test results for hepatitis B or hepatitis C as detailed in the protocol - Known history of HIV seropositive status - Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix, squamous carcinoma of the skin, adequately controlled limited basal cell skin cancer, or synchronous primary endometrial cancer or prior primary endometrial cancer - Untreated or active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control) - Pregnancy or breastfeeding - Known history of NaPi2b deficiency (for example, congenital alveolar microlithiasis or testicular microlithiasis) - History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins) - Metabolic dysfunction, physical examination finding, or clinical laboratory find giving reasonable suspicion of a disease or condition that contraindicated use of an investigational drug or may render the participant at high risk from treatment complications |
| 50 | NCT01992952 | active, not recruiting | 0.35881078243255615 | 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 | |
| 51 | NCT01998399 | terminated | poor enrollment, unable to meet recruitment goals | 0.41095656156539917 | phase 2 | ['community acquired pneumonia, severe'] | ["['A01.03', 'A02.22', 'A54.84', 'B01.2', 'B06.81', 'B77.81', 'J12.0']"] | ['ticagrelor', 'placebo'] | ['[H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. Patients will have new "severe" CAP as defined by a. New (within 72 hours of hospital admission) radiographic finding consistent with pneumonia and admission or planned admission to an ICU for: i. Mechanical Ventilation (invasive or non-invasive) OR ii. Vasopressors (dobutamine and phosphodiesterase are not considered vasopressors for this criteria) OR iii. ICU admission due to severe respiratory distress or arterial desaturation. b. At least two of the following; i. recent increase in dyspnea ii. increased sputum production iii. change of character of sputum iv. White Blood Cells > 12,000 or < 4,000 cells/mm3 or >10% bands v. Body temperature >38ºC or <36ºC (any route) Exclusion Criteria: 1. More than 72 hours have passed since meeting required inclusion criteria. 2. Development of pneumonia after 72 hours of current hospitalization. 3. Underlying disease likely to cause mortality within 90 days of randomization. 4. A resident in a hospital, not nursing home, within 30 days prior to development of pneumonia. 5. Patients who are moribund (not expected to live for more than 48 hours). 6. No consent/inability to obtain consent from patient or surrogate. 7. Patient's physician is unwilling to have patient enter the study. 8. Age less than 50 years. 9. Pregnancy. 10. Breast feeding. 11. Underlying immunodeficiency (e.g. HIV, neutropenia, active hematologic malignancy, functional or anatomical asplenia and hypogammaglobulinemia). 12. Patient, surrogate, or physician not committed to full support (exception: a patient will not be excluded if he/she will receive all supportive care except for attempts at resuscitation from cardiac arrest). 13. Unable to receive or unlikely to absorb enteral study drug (e.g., patients with partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and short bowel syndrome). 14. Hepatic impairment a. Child Pugh score > 7 using data from outpatient setting 15. Conditions that increase the risk of bleeding, e.g.: 1. Surgery or the likely need for surgery during study, or evidence of active bleeding postoperatively (ICU procedures such as line placement, tracheostomy and chest tubes are not to be considered for this exclusion); 2. A history of severe head trauma requiring hospitalization or intra-cranial surgery within 3 months; 3. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system, hemorrhagic stroke or intracranial hemorrhage, or congenital bleeding diathesis; 4. Gastrointestinal bleeding within 6 weeks before the study unless a corrective procedure has been performed; 5. Recent trauma considered to increase the risk of bleeding. 16. Chronic renal disease requiring renal replacement therapy. 17. Creatinine > 3 mg/dL. 18. Platelet count < 50,000 /mm3. 19. Use of a P2Y12 inhibitor within the 3 months prior to randomization or physician intent to initiate one of the CYP3A inhibitors, e.g. ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, atazanovir, saquinavir, nelfinavir, indinavir, or telithromycin. 20. Use of CYP3A inducers, e.g. rifampin, phenytoin, carbamazepine and phenobarbital. 21. Simvastatin or Lovastatin doses > 40 mg per day. 22. Digoxin use. 23. Receiving aspirin and physician and/or patient unwilling to reduce aspirin dose to <100 mg per day. 24. Daily Non-steroidal anti-inflammatory drugs (NSAID) use as an outpatient (other than Aspirin (ASA) as above). 25. Sick Sinus Syndrome, 2nd or 3rd degree heart block, bradycardia induced syncope - unless pacemaker in place. 26. Otherwise unsuitable for participation in the opinion of the investigator (i.e., homeless, non-compliant, etc.). |
| 52 | NCT02001688 | completed | 0.7350322008132935 | phase 2 | ['alpha-1 antitrypsin deficiency'] | ["['E88.01']"] | ['kamada-aat for inhalation, 80mg', 'placebo', 'kamada-aat for inhalation, 160mg'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Male or female patients between 18 and 65 years of age (inclusive). - Able and willing to sign informed consent. - Males, and non-pregnant, non-lactating females whose screening pregnancy test is negative and who are using contraceptive methods deemed reliable by the investigator or who are post-menopausal or surgically sterilized. - Diagnosis of alpha1-antitrypsin deficiency [only individuals with a ZZ or Z null classification]. - Forced expiratory volume in one second (FEV1) ≥ 50% of predicted post bronchodilator - No respiratory exacerbations within 6 weeks of baseline. Subjects can be re-screened if exacerbations exist at the time of enrollment. - No signs of chronic and/or acute Hepatitis A, Hepatitis B, Hepatitis C, HIV infection and Parvovirus B19, by NAT (for Parvovirus B19, nucleic acid testing (NAT) result must be < 10^4 IU/mL). - No significant abnormalities in serum hematology, serum chemistry, serum inflammatory / immunogenic markers and urinalysis. - No significant abnormalities in ECG. - Not on intravenous augmentation therapy for at least 8 weeks prior to initial dosing with study drug/placebo and willing to forego intravenous augmentation therapy for the duration of the study. Exclusion Criteria: - Clinically significant intercurrent illnesses (except for respiratory or liver disease secondary to AAT deficiency), including: cardiac, hepatic, renal, endocrine, neurological, hematological, neoplastic, immunological, skeletal or other) that in the opinion of the investigator, could interfere with the safety, compliance or other aspects of this study. Patients with well-controlled, chronic diseases could possibly be included after consultation with the treating physician and the sponsor. - History of life threatening allergy, anaphylactic reaction, or systemic response to human plasma derived products. - History of life threatening transfusion reactions. - History of lung transplant. - Current or previous (up to 8 weeks from baseline) use of AAT augmentation therapy or by any other route - Current use of oral or parenteral glucocorticoids in doses exceeding 10mg of prednisone daily or equivalent generics (substance and dose). - Any lung surgery within the past two years. - On any thoracic surgery waiting list. - Active smoking during the last 12 months from screening date. - Pregnancy or lactation. - Woman of child-bearing potential not taking adequate contraception deemed reliable by the investigator. - Presence of psychiatric/ mental disorder or any other medical disorder which might impair the patient's ability to give informed consent or to comply with the requirements of the study protocol. - Evidence of alcohol abuse or history of alcohol abuse or illegal and/or legally prescribed drugs. - Immunoglobulin A (IgA) Deficiency. - Inability to undergo bronchoscopy. - Allergy to lidocaine or any other medicines used in the bronchoscopy process - Exacerbation of chronic obstructive pulmonary disease (COPD) in the previous 6 weeks. - Participation in another clinical trial involving investigational medication or interventional treatment within 30 days prior to baseline visit. - Participation in observational clinical trial which involves any invasive procedure scheduled to occur during the AAT inhaled study period. If participating in an observational clinical trial that already completed all diagnostic procedures (e.g. liver biopsy), any adverse events (AEs) experienced must have returned to baseline within 30 days prior to baseline visit. - Inability to attend scheduled clinic visits and/or comply with the study protocol. - Any other factor that, in the opinion of the investigator, would prevent the patient form complying with the requirements of the protocol. | |
| 53 | NCT02002052 | terminated | insufficient accrual | 0.2909037172794342 | phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['concurrent platinum-based chemotherapy'] | ['[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: - Age 18 or older - Willing to provide informed consent - ECOG performance status 0-2 - Histologically confirmed non-small cell lung carcinoma - Locally advanced Stage IIIA or IIIB lung carcinoma according to AJCC 7th edition - History of at least 10-pack-years of smoking - Not undergoing surgical resection - Assessment by medical oncologist and radiation oncologist, with adequate bone marrow, hepatic and renal function for administration of platinum-based chemotherapy Exclusion Criteria: - Contraindications to MRI - Serious medical comorbidities (such as unstable angina, sepsis) or other contraindications to radiotherapy or chemotherapy - Prior history of lung cancer within 5 years - Prior thoracic radiation at any time - Metastatic disease. Patients who present with oligometastatic disease where all metastases have been ablated (with surgery or radiotherapy) are candidates if they are receiving chemoradiotherapy to the thoracic disease with curative intent. - Inability to attend full course of radiotherapy or follow-up visits - Pregnant or lactating women |
| 54 | NCT02006472 | completed | 0.5669822692871094 | phase 2 | ["huntington's disease"] | ["['G10']"] | ['pridopidine'] | ['CCCN1CCC(CC1)C1=CC=CC(=C1)S(C)(=O)=O'] | Inclusion Criteria: - Diagnosis of HD based on the presence of >/= 36 CAG repeats - Male or female age ≥21 years, with an onset of HD after 18 years' old. - Females of child bearing potential have to be compliant in using adequate birth control throughout the duration of the study - Body weight ≥50 kg - Sum of >/= 25 points on the UHDRS-TMS and UHDRS Independence Score below 90% - Able and willing to provide written informed consent prior to any study related procedure. - Willing to provide a blood sample for genetic analyses - Willing and able to take oral medication and able to comply with the study specific procedures. - Ambulatory, being able to travel to the study centre, and judged by the investigator as likely to be able to continue to travel for the duration of the study. - Availability and willingness of a caregiver, informant or family member to accompany the patient to the clinic at study, and the suitability of the caregiver should be judged by the investigator. - Other criteria apply, please contact the investigator for more information. Exclusion Criteria: - Patients with clinically significant heart disease at the screening visit - Treatment with tetrabenazine within 6 weeks of study screening - Patients with a history of epilepsy or of seizures within the last 5 years - Have other serious medical illnesses in the opinion of the investigator may put the patient at risk when participating in the study or may influence the results of the study or affect the patient's ability to take part in the study - Patients receiving medications (within the last 6 weeks prior to screening) that have been proven to prolong QT interval or who may require such medications during the course of the study such as but not limited to non allowed anti psychotic medications, tricyclic antidepressants and/or Class I antiarrhythmics - Patients receiving medications (within the last 6 weeks prior to screening) that are metabolized by CYP2D6 and have the potential of reducing seizure threshold - Other criteria apply, please contact the investigator for more information | |
| 55 | NCT02006628 | completed | 0.5841959714889526 | phase 2 | ['schizophrenia', 'schizophrenia-related psychotic disorder'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']", "['F23', 'F24', 'F12.159', 'F12.259', 'F30.10', 'F30.11', 'F30.12']"] | ['placebo', 'gwp42003'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'CCCCCC1=CC(O)=C([C@@H]2C=C(C)CC[C@H]2C(C)=C)C(O)=C1'] | Inclusion Criteria (all must be fulfilled): - Participant gave written informed consent for participation in the study and did not require involuntary treatment. - Participant was male or female aged 18 to 65 years. - Participant was able (in the investigator's opinion) and willing to comply with all study requirements. - Participant was diagnosed with schizophrenia or a related psychotic disorder (such as schizoaffective or schizophreniform disorder) as defined by the Diagnostic and Statistical Manual of Mental Disorders Version 4. - Participant was treated for a minimum of four-weeks and was on a stable dose of his or her current anti-psychotic (AP) medication. - Participant showed the capacity to respond at least partially to first line AP medication in the opinion of the investigator. - Participant remained stable on his or her dose of AP and concomitant medications for the duration of the study, in the opinion of the investigator. - Participant was willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable in individual countries. - Participant was willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study. Exclusion Criteria (any of the following): - Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the Investigational Medicinal Product (IMP). - Participant had a Positive and Negative Symptom Scale total score of <60 at Day 1. - Participant presented with a current clinical picture and/or history that is consistent with: i. delirium or dementia. ii. acute drug induced psychosis. iii. bipolar disorder. - Participant was taking more the one AP medication during the study. - Female participants of child bearing potential and male participants whose partner was of child bearing potential, unless willing to ensure that they or their partner used effective contraception, for example, oral contraception, double barrier, intra-uterine device, during the study and for three months thereafter (a male condom was not used in conjunction with a female condom). - Female participant who was pregnant, lactating, or planning pregnancy during the course of the study and for three months thereafter. - Participants who had received an IMP within 30 days prior to the screening visit. - Participants who had any other significant disease or disorder which, in the opinion of the investigator, either put the participant at risk because of participation in the study, or may have influenced the result of the study, or the participant's ability to participate in the study. - Participant had any abnormalities following a physical examination that, in the opinion of the investigator, prevented the participant from safe participation in the study. - Participant was unwilling to abstain from donation of blood during the study. - Participant had travelled outside the country of residence during the study. - Participant previously randomized into this study. | |
| 56 | NCT02008006 | terminated | insufficient recruitment and unavailability of the treatment | 0.46302518248558044 | phase 2 | ['follicular lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['beeam'] | ['NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O'] | INCLUSION CRITERIA: - Histologically confirmed follicular lymphoma relapsed (WHO grade 1, 2, 3a) - Patients aged from 18 to 65 years - First or second chemosensitive relapses after salvage therapy (rituximab-chemotherapy) based on 2007 Cheson et al. international response criteria (CR and PR) before the decision of BeEAM (HDT) and ASCT (autologous stem cell transplantation) treatment - Eligible for ASCT - Autologous graft with a minimum of a number of cluster of differentiation 34 (CD34+) cells 3.0x106/kg. - Autologous transplantation will be performed in hematopoietic stem cell transplantation authorized centers. - Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 to 2 - Minimum life expectancy of 3 months - Cardiovascular baseline corrected QT interval F ( QTcF) ≤ 450 msec (male) or 470 msec (female) - Medications that may cause corrected QT interval (QTc) interval prolongation should be avoided by patients entering on trial - Normal organ and marrow function as defined below: - Absolute neutrophil count ≥ 1.5 G/l - Platelet count ≥ 100 G/l or > 75 G/l if the bone marrow is involved - Creatine clearance ≥ 50 ml/min - Serum Glutamate Oxaloacetate Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5 x ULN if liver metastasis - Total bilirubin ≤ 1.5 x ULN - Cardiac ejection fraction greater than 50% by echocardiogram or multiple gated acquisition scan (MUGA scan) - Negative serum pregnancy test for women of childbearing potential* - Pregnancy tests will include a negative serum pregnancy test (with a sensitivity of at least 25 mill-International Unit (mIU)/ml) - Women of childbearing potential* and men must agree to use adequate contraception prior to study entry, for the duration of study participation and until 6 months after the end of treatment - Female patients who meet at least one of the following criteria are defined as women of non-childbearing potential: - ≥ 50 years old and naturally amenorrheic for ≥ 1 year - Permanent premature ovarian failure confirmed by a specialist gynecologist - Previous bilateral oophorectomy - XY genotype, Turner's syndrome or uterine agenesis - Female patients who do not meet at least of the above criteria are defined as women of childbearing potential - Ability to understand and willingness to sign a written informed consent document - Covered by a medical insurance - Signed informed consent EXCLUSION CRITERIA: - Transformed follicular lymphoma - Prior autologous or allogeneic transplantation - Presence of a none chemosensitive disease before HDT according to 2007 Cheson et al. international response criteria (stable or progressive disease) - Contraindication to any drug contained in the chemotherapy regimens - Bone marrow infiltration > 25% before HDT+ASCT - Positive HIV, Hepatitis C Virus (HCV) and Hepatitis B (HBs)Ag serologies - Current bacterial, viral or fungal infection - Treatment with any investigational drug within 30 days before enrolment - Major surgery within 30 days before enrolment - Participation in another clinical trial within 30 days prior to enrolment in the study and during study - Any serious active disease or co-morbid medical conditions that would interfere with therapy - 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 subject has been free of the disease for ≥ 5 years - Known or suspected hypersensitivity to any of the agents or excipients of the regime under evaluation - Concomitant treatment with chemotherapy or immunotherapy or radiotherapy - Yellow fever vaccination (attenuated virus vaccine ) - Pregnant or lactating female - Abnormalities in cardiac function or clinically significant heart disease such as acute myocardial infarction or unstable angina within 6 months prior to the start of study treatment, heart failure New York Heart Association (NYHA) class III or IV, uncontrolled hypertension or a history of antihypertensive treatment poor compliance, uncontrolled arrhythmias with treatment, except extrasystoles or minor conduction disorders - Known involvement of the central nervous system by lymphoma - History of chronic liver disease - History of hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) - Excessive alcohol use |
| 57 | NCT02008318 | completed | 0.3427209258079529 | phase 2/phase 3 | ['myelodysplastic syndromes'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['galunisertib', 'placebo'] | ['CC1=CC=CC(=N1)C1=NN2CCCC2=C1C1=C2C=C(C=CC2=NC=C1)C(N)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Confirmed diagnosis of MDS based on the World Health Organization (WHO) criteria - Participants with 5q deletions are allowed only if they have failed or are intolerant of lenalidomide treatment - Participants must have a Revised International Prognostic Scoring System (IPSS-R) category of very low-, low-, or intermediate-risk disease - In the 8 weeks prior to registration, participants in phase 2 should have anemia with Hb ≤10.0 g/dL (based on the average of 2 baseline measurements and untransfused for at least 1 week) with or without red blood cell (RBC) transfusion dependence confirmed for a minimum of 8 weeks before enrollment - For phase 3, participants should have anemia with RBC transfusion dependence confirmed within 8 weeks before enrollment - Performance status ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: - No history of moderate or severe cardiac disease - No prior history of acute myeloid leukemia (AML) | |
| 58 | NCT02008773 | completed | 0.453510582447052 | phase 2 | ['schizophrenia'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']"] | ['valacyclovir hci 500 mg tablets', 'placebo'] | ['CC(C)[C@H](N)C(=O)OCCOCN1C=NC2=C1NC(N)=NC2=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - 18 to 40 years of age at study entry. - Able to give written informed consent. - DSM IV-TR Diagnosis of schizophrenia, schizophreniform, or schizoaffective disorder as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID) - Onset of schizophreniform disorder, schizophrenia, or schizoaffective disorder within the past eight years as defined by first medical records documentation of these conditions - Outpatient or inpatient. - Clinical stability as defined by: 1. CGI-S score of less than or equal to 4 (moderately ill) at randomization AND 2. Participants must not have experienced an exacerbation of their illness within 4 weeks prior to randomization leading to an intensification of psychiatric care in the opinion of the investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND 3. Antipsychotic treatment stability for at least 4 weeks prior to randomization (no change in antipsychotic dosing, addition of any new antipsychotic medication, or discontinuing an antipsychotic medication) - Fluent in English. - Female participants of childbearing potential must test negative for pregnancy at screening visit and agree to use a single, effective, medically acceptable method of birth control for the duration of the study. Exclusion Criteria: - Known IQ less than 70 as determined by medical history. - IV drug use within previous three month prior to study entry. - Any serious active medical condition that affects brain or cognitive functioning (e.g., epilepsy, serious head injury, brain tumor or other neurological disorder) in the investigator's opinion. - Known medical history of Human Immunodeficiency Virus (HIV) - Receipt of valacyclovir or chemically-related medication within 2 weeks prior to randomization. - History of hypersensitivity to valacyclovir or acyclovir as determined by self-report and medical history. - DSM-IV diagnosis of substance dependence within 3 months of study entry (with the exception of nicotine or caffeine dependence). - Participants who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to screening AND participants currently receiving treatment (within 1 dosing interval plus 4 weeks) with an investigational depot formulation of an antipsychotic medication. - Females who are pregnant or planning to become pregnant or breastfeeding or planning to do so during the study period. - Participants with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, COPD, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic or renal disease, renal including renal failure, gastroenterologic, respiratory, endocrinologic, neurologic, hematologic including thrombotic thrombocytopenia purpura/hemolytic uremic syndrome, or infectious diseases - Participants who require concomitant treatment with any other medication other than those allowed as specified in Attachment 2, or with any other medication specifically excluded in Attachment 2. - Clinically significant electrocardiogram (ECG) abnormality prior to randomization as defined by: participants with a corrected QT interval (Bazett's; QTcB) >450 msec (male) or >470 msec (female) prior to randomization. Repeat ECGs will be conducted at the discretion of the principal investigator or medical designee. - Test positive for (1) Hepatitis C virus antibody, (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody. - Participants with moderate to severe renal impairment as defined by creatinine clearance (CrCl) < 60 ml/min (measured by the Cockcroft-Gault equation) at screening. - Participants with hepatic impairment as defined by liver transaminases or total bilirubin > 3 × upper limit of normal (ULN). - Participants considered a high risk for suicidal acts - active suicidal ideation as determined by clinical interview OR any suicide attempt in 90 days prior to screening. - Participants who demonstrate overtly aggressive behavior or who are deemed to pose a homicidal risk in the investigator's opinion. - Participants currently receiving cognitive remediation therapy at time of study entry - Participants who have had electroconvulsive therapy (ECT) within 12 months of study entry or who will have ECT at any time during the study. | |
| 59 | NCT02011451 | withdrawn | unable to enroll | 0.40729817748069763 | phase 2 | ['multiple sclerosis'] | ["['G35', 'C81.18']"] | ['95% pure ecgc capsules 200mg', 'placebo comparator:'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Diagnosis of MS by McDonald criteria - Relapsing-remitting MS or secondary progressive MS - Stable therapy with Copaxone, Rebif, Betaseron or Avonex 30 mcg for at least six months - EDSS Score less than or equal to 7.0 - Ages 18-60. - Participants must have normal organ and marrow function as defined below: - Leukocytes ≥3,000/µL - Absolute neutrophil count ≥1,500/µL - Platelets ≥100,000/µL - Total bilirubin ≤local upper limit of normal - AST (SGOT) ≤local upper limit of normal - ALT (SGPT) ≤local upper limit of normal - Creatinine ≤local upper limit of normal Exclusion Criteria: - MS relapse within the 30 days prior to enrollment - A primary progressive form of MS. - Previous treatment prior to study entry as follows: complete radiation ablation of the bone marrow or anti-CD4 antibody treatment (Campath) at any time; mitoxantrone, cyclophosphamide, Natalizumab or other immunomodulatory or immunosuppressant therapies except the DMT's included in the inclusion criteria and methylprednisone for relapses within prior nine months. - History of renal or liver disease. - Consumption of green tea or supplements containing green tea or tea extract within 30 days prior to enrollment. - Participants may not participate in any other clinical trial involving investigational agents during the study, or within six months prior to enrolling in the study. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to Polyphenon E, tea, or any of the inactive ingredients present in the active or placebo capsules, including gelatin. - History of allergic reactions to gadolinium or any other condition contraindicated for MRI. - Uncontrolled, clinically-relevant active illness (aside from MS) 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. - Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study - Inability to complete the baseline MRI scan - Pregnant women - Any underlying predisposition to gastrointestinal bleeding (peptic ulcer disease, gastritis, diverticulitis, colitis, hemorrhoids) |
| 60 | NCT02013128 | completed | 0.4180578291416168 | 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 | |
| 61 | NCT02013362 | completed | 0.45688337087631226 | 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. | |
| 62 | NCT02013375 | terminated | 0.32461339235305786 | phase 2 | ['sickle cell disease'] | ["['D57.1', 'D57.20', 'D57.212', 'D57.219', 'D57.211', 'D57.213', 'D57.218']"] | ['alemtuzumab', 'cyclophosphamide', 'sirolimus'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'ClCCN(CCCl)P1(=O)NCCCO1', 'CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2'] | Patient Eligibility: - Patients with sickle cell disease are eligible if they have any of the following complications: - Stroke or central nervous system event lasting longer than 24 hours - Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, or hospital admissions. - Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits - Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events - Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy - Bilateral proliferative retinopathy with major visual impairment in at least one eye - Osteonecrosis of 2 or more joints - Sickle cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin > 300 mg/g creatinine) - Pulmonary hypertension, defined by a mean pulmonary artery pressure > 25mmHg - Age 16-60 years - Karnofsky performance status of 60 or higher - Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% - Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration) - Estimated GFR ≥ 50mL/min as calculated by the modified MDRD equation - ALT ≤ 3x upper limit of normal - HIV-negative - Patient is pregnant - Patient is able and willing to sign informed consent - Patient has an HLA-haploidentical relative | |
| 63 | NCT02014376 | completed | 0.5575017333030701 | phase 2 | ['epidermolysis bullosa'] | ["['Q81.0', 'Q81.1', 'Q81.2', 'Q81.8', 'Q81.9', 'L12.30', 'L12.35']"] | ['sd-101 dermal cream (3%)', 'sd-101 dermal cream (6%)', 'vehicle (sd-101 0%)'] | ['CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: - Informed Consent form signed by the participant or the participant's legal representative; if the participant is under the age of majority but capable of providing assent, signed assent from the participant. - Participant (or caretaker) was willing to comply with all protocol requirements. - Diagnosis of Simplex, Recessive Dystrophic, or Junctional non-Herlitz EB. - Participants 6 months of age and older. - Participants had 1 target wound within a prespecified size range at study entry. - Target wound was at least 21 days or older. Exclusion Criteria: - Participants who did not meet all the entry criteria outlined in inclusion criteria. - Selected target wound had clinical evidence of local infection. - Use of any investigational drug within 30 days before enrollment. - Use of immunotherapy or cytotoxic chemotherapy within 60 days before enrollment. - Use of systemic or topical steroidal therapy within 30 days before enrollment (inhaled steroids and ophthalmic drops containing steroids were allowed). - Use of systemic antibiotics within 7 days before enrollment. - Current or former malignancy. - Arterial or venous disorder resulting in ulcerated wounds. - Diabetes mellitus. - Pregnancy or breastfeeding during the study (a urine pregnancy test was performed at screening for female participants of childbearing potential). - Females of childbearing potential who were not abstinent and not practicing a medically acceptable method of contraception. - Known history of cardiac, hepatic, or renal disease. | |
| 64 | NCT02016898 | completed | 0.7045087218284607 | phase 2 | ['primary open angle glaucoma'] | ["['H40.1130', 'H40.1131', 'H40.1132', 'H40.1133', 'H40.1134', 'H40.1110', 'H40.1111']"] | ['mitomycin-c'] | ['CO[C@]12[C@H]3N[C@H]3CN1C1=C([C@H]2COC(N)=O)C(=O)C(N)=C(C)C1=O'] | Inclusion Criteria: 1. Men or women aged 18 years and older at screening. 2. Diagnosis of chronic angle-closure glaucoma or open-angle glaucoma, phakic or pseudophakic, with visual field or optic disc changes characteristic of glaucoma. 3. Suitable candidate for trabeculectomy with Ex-PRESS glaucoma filtration device with MMC in the superonasal quadrant in the study eye which the physician deems as medically necessary. 4. Capable and willing to provide consent Exclusion Criteria: 1. Unable or unwilling to provide consent 2. Any previous ocular surgeries in the study eye preventing placement of the trabeculectomy with Ex-PRESS glaucoma filtration device with mitomycin-C in the superonasal quadrant 3. Any previous glaucoma drainage devices in the study eye 4. Any abnormality other than glaucoma in the study eye that could affect applanation tonometry. 5. Presence or history of any abnormality or disorder that could interfere with the study procedure or prevent the successful completion of the study. 6. Presence or history of uveitis within 10 years or any other ocular infection or inflammation within 14 days before day 1. 7. Any significant unstable cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease. 8. Known Pregnancy or Breastfeeding Physical and Laboratory Findings 9. Conjunctival scarring precluding a superonasal implantation location. 10. Vitreous in the anterior chamber. 11. Abnormality preventing reliable applanation tonometry in the study eye. | |
| 65 | NCT02017964 | active, not recruiting | 0.2883692979812622 | phase 2 | ['desmoplastic/nodular medulloblastoma', 'medulloblastoma', 'medulloblastoma with extensive nodularity', 'nevoid basal cell carcinoma syndrome', 'untreated childhood medulloblastoma'] | ["['F80.81', 'F84.3', 'F93.8', 'F93.9', 'R62.0', 'E71.520', 'F64.2']"] | ['carboplatin', 'cyclophosphamide', 'etoposide', 'methotrexate', 'vincristine sulfate'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'ClCCN(CCCl)P1(=O)NCCCO1', 'OCCOCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1', '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', '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: - Patients must be newly diagnosed and have a confirmed histologic diagnosis of nodular desmoplastic (ND) medulloblastoma or medulloblastoma with extensive nodularity (MBEN) from rapid central pathology screening review; please note: patients with Gorlin syndrome are eligible - Patient must have negative lumbar cerebrospinal fluid (CSF) cytology (lumbar CSF must be obtained unless medically contraindicated); CSF cytology for staging should be performed preferably no sooner than 14 days post operatively to avoid false positive CSF, ideally, CSF should be obtained between day 14 and day 21 to allow for final staging status before enrollment onto the study; Note: patients with positive CSF cytology obtained prior to 14 days after surgery may have cytology repeated to determine eligibility and final CSF status - Patients must have: - Pre-operative cranial magnetic resonance imaging (MRI) (recommended with gadolinium) or pre-operative computed tomography (CT) (recommended with contrast) - Post-operative cranial MRI with and without gadolinium within 72 hours of surgery - Spinal MRI pre-op with and without gadolinium or post-op with and without gadolinium preferably within 72 hours of surgery - Patients must be enrolled on study within 31 days of definitive surgical resection at which time tissue is acquired to determine a diagnosis; patients must be enrolled before treatment begins; the date protocol therapy is projected to start must be no later than five (5) calendar days after the date of study enrollment; patients who are started on protocol therapy on a Phase II study prior to study enrollment will be considered ineligible - Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Lansky for patients =< 16 years of age - Patients must have a life expectancy of >= 8 weeks - Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry - Peripheral absolute neutrophil count (ANC) >= 1000/uL - Platelet count >= 100,000/uL (transfusion independent) - Hemoglobin >= 10.0 g/dL (may receive red blood cell [RBC] transfusions) - Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows: - 1 month to < 6 months: 0.4 mg/dL - 6 months to < 1 year: 0.5 mg/dL - 1 to < 2 years: 0.6 mg/dL - 2 to < 6 years: 0.8 mg/dL - Total bilirubin =< 1.5 x upper limit of normal (ULN) for age - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age - Central nervous system function defined as: - Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled - Patients must not be in status, coma or assisted ventilation prior to study enrollment Exclusion Criteria: - Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar CSF cytology are not eligible - Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids | |
| 66 | NCT02021292 | completed | 0.42063581943511963 | phase 2 | ['chronic thromboembolic pulmonary hypertension'] | ["['I27.24']"] | ['macitentan', 'placebo'] | ['CCCNS(=O)(=O)NC1=C(C(OCCOC2=NC=C(Br)C=N2)=NC=N1)C1=CC=C(Br)C=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Written informed consent - Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the obstruction being surgically inaccessible (i.e., distal disease). - Female of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception. Exclusion Criteria: - Previous pulmonary endarterectomy. - Recurrent thromboembolism despite sufficient oral anticoagulants. - Symptomatic acute pulmonary embolism in the 6-month period prior to randomization. - Known moderate-to-severe restrictive lung disease (i.e., TLC < 60% of predicted value) or obstructive lung disease (i.e., FEV1 < 70% of predicted, with FEV1/FVC < 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema). - Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements in the 3-month period prior to Screening visit or during the Screening period. | |
| 67 | NCT02021370 | completed | 0.4388654828071594 | phase 2 | ['anemia', 'renal insufficiency, chronic'] | ["['D53.2', 'D64.9', 'D46.4', 'D53.0', 'D53.9', 'D61.3', 'D61.9']", "['N25.0', 'Q61.4', 'N23', 'N26.9', 'P96.0', 'Q60.0', 'Q60.1']"] | ['bay85-3934', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Women without childbearing potential - Male or female subjects ≥ 18 years of age with anemia of chronic kidney disease (CKD) at screening - Estimated glomerular filtration rate of < 60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] or the formula according to Matsuo, et al) - Not on dialysis and not expected to begin dialysis during the treatment period of the study (at least 16 weeks from randomization) - Not treated with any erythropoiesis-stimulating agent (ESA) within 8 weeks before randomization - Mean screening Hb concentration </= 10.5 g/dL - Body weight of 45 kg to 125 kg, inclusive, at screening Exclusion Criteria: - Subjects with significant acute or chronic bleeding, such as overt gastrointestinal bleeding - Chronic inflammatory disease that could impact erythropoiesis (e.g., systemic lupus erythematosis, rheumatoid arthritis, celiac disease) even if it is currently in remission - Previous or concurrent cancer except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis, and T1) or any cancer curatively treated > 3 years prior to randomization - Subjects treated with any ESA within the 8 weeks before randomization - Red blood cell (RBC) containing transfusion within the 8 weeks before randomization - History of cardio- (cerebro-) vascular events (e.g., unstable angina, myocardial infarction, stroke, transient ischemic attack, deep vein thrombosis, pulmonary embolism) within the last 6 months from initial screening visit - Severe rhythm or conduction disorders (e.g., HR < 50 or > 110 bpm, atrial flutter, prolonged QT > 500 msec, third degree atrioventricular [AV] block) - New York Heart Association Class III or IV congestive heart failure - Severe hepatic insufficiency (defined as alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 3 x the upper limit of normal [ULN], total bilirubin > 2 mg/dL, or Child-Pugh B and C) or active hepatitis, in the investigator's opinion | |
| 68 | NCT02021669 | completed | 0.539434015750885 | phase 2 | ['depression'] | ["['F32.A', 'F53.0', 'P91.4', 'Z13.31', 'Z13.32']"] | ['omega-3 supplement', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Documented coronary heart disease - Diagnosis of major depression based on structured interview Exclusion Criteria: - Moderate to severe cognitive impairment - Meets DSM-5 criteria for depressive disorder due to a general medical condition or medication - Major Axis I psychiatric disorder other than unipolar depression or an anxiety disorder, a high risk of suicide, or current substance abuse other than tobacco; - Not expected to survive one year or physically unable to tolerate the study protocol - Known sensitivity to sertraline or omega-3, or an allergy to fish oil or shellfish - Taking an antidepressant or an omega-3 supplement at baseline - Exempted by their cardiologist or primary care physician - Refuses to provide informed consent - Participating in a competing protocol or trial | |
| 69 | NCT02023697 | completed | 0.5088077187538147 | phase 2 | ['prostatic neoplasms'] | ["['B38.81', 'N42.31', 'Z87.430', 'N40.0', 'N40.1']"] | ['radium-223 dichloride (xofigo, bay88-8223)'] | ['Cl[223Ra]Cl'] | Inclusion Criteria: - Histologically or cytologically confirmed adenocarcinoma of the prostate - Castration-resistant disease defined as: - Serum testosterone level: ≤ 50 ng/dL (1.7 nmol/L) - Bilateral orchiectomy or maintenance on androgen ablation therapy with luteinizing-hormone-releasing hormone (LHRH) agonist or antagonist, or polyestradiol phosphate - Serum PSA (Prostate specific antigen) progression defined as 2 subsequent increases in PSA over a previous reference value (a minimum of 2 ng/mL [μg/L]) OR - Radiographic evidence of disease progression in bone (according to Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) with or without PSA progression - Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2. In case of ECOG PS 2, the PS has to be due to metastatic prostate cancer to the bone. - Two or more skeletal metastases (≥ 2 hot spots) on bone scintigraphy within 8 weeks of randomization Exclusion Criteria: - History of visceral metastasis, or visceral metastases - Lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter - Central nervous system (CNS) metastases - Treatment with cytotoxic chemotherapy for prostate cancer within the previous 4 weeks prior to randomization, or planned treatment with cytotoxic chemotherapy agents for prostate cancer during the treatment period or follow-up - Chronic conditions associated with non-malignant abnormal bone growth (e.g. confirmed Paget's disease of bone) - Prior treatment with radium-223 dichloride - Prior systemic radiotherapy and hemibody external radiotherapy | |
| 70 | NCT02024932 | completed | 0.5720441937446594 | phase 2 | ['spinal and bulbar muscular atrophy'] | ["['G71.00', 'G71.02', 'G71.11', 'G12.9', 'G71.09', 'N36.44', 'G12.1']"] | ['bvs857', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Key Inclusion Criteria: - Genetic diagnosis of SBMA with symptomatic muscle weakness - Able to complete 2 minute timed walk - Serum IGF-1 level less than or equal to 170 ng/mL Key Exclusion Criteria: - Medically treated diabetes mellitus or known history of hypoglycemia - History of Bell's palsy - Treatment with systemic steroids > 10 mg/day (or equivalent dose); androgens or androgen reducing agents; systemic beta agonists; or other muscle anabolic drugs within the previous 3 months - History of cancer, other than non-melanomatous skin cancer - Retinopathy - Papilledema Other protocol defined inclusion/exclusion criteria may apply | |
| 71 | NCT02025985 | completed | 0.290482759475708 | phase 2 | ['ovarian carcinoma', 'endometrial carcinoma', 'cervical carcinoma'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['selinexor'] | ['FC(F)(F)C1=CC(=CC(=C1)C1=NN(\\C=C/C(=O)NNC2=NC=CN=C2)C=N1)C(F)(F)F'] | Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - Adequate hematologic function defined as: - platelets ≥125*10^9 per liter (/L) - hemoglobin ≥5.59 millimoles per liter (mmol/L) or 9 grams per deciliter (g/dL) - Absolute neutrophil count (ANC) ≥1.5*10^9/L - White blood cells (WBC) count ≥3.0*10^9/L - Up to 5 percent (%) deviation is tolerated. Transfusions and growth factors are allowed. - Adequate liver function defined as adequate hepatic function within 14 days prior to Cycle 1 Day 1: total bilirubin <2 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome, who must have a total bilirubin of <3 times ULN), aspartate aminotransferase (AST) <2.0 times ULN, and alanine aminotransferase (ALT) <2.0 times ULN. In the case of known (radiologically and/or biopsy- documented) liver metastasis, AST <5.0 times ULN and ALT <5.0 times ULN is acceptable. Up to 10% deviation is acceptable. - Renal function defined as a calculated or measured glomerular filtration rate ≥30 milliliter per minute (mL/min). - The participant has recovered to Grade less than or equal to (≤) 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 (NCI-CTCAE v4.03) from the effects of recent surgery, radiotherapy, chemotherapy, hormonal therapy, or other targeted therapies, with the exception of alopecia. The exceptions for such effects are allowed lab values of ≤Grade 2 specified elsewhere in these inclusion criteria. - Life expectancy of at least 12 weeks. - Able to swallow and retain oral medication. - Participants must give informed consent according to the rules and regulations of the individual participating sites. - Negative serum pregnancy test in women of childbearing potential within 14 days of first dose of treatment, and participants of childbearing potential must agree to use effective contraception during treatment up to 3 months from last dose. Fertile male partners must be willing and able to use effective non-hormonal means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment. - The participant must be recovered from any prior treatment/major operation. The treatment/major operation must be performed at least 4 weeks prior to start of study drug. Palliative radiotherapy is permitted until one week prior to the start of study drug. - Only incurable participants with histologically or cytologically proven primary tumor and objective documentation of disease progression on prior treatment by computerized tomography (CT)/ magnetic resonance imaging (MRI) may be enrolled. - Ovarian, fallopian tube, or peritoneal carcinoma: both platinum refractory* and platinum resistant** participants, who have received ≥1 line of chemotherapy for relapsed disease (i.e., ≥2 lines of chemotherapy in total). *Platinum refractory is defined as progression during or within 4 weeks of last treatment with a platinum-containing therapy. **Platinum resistant is defined as relapse 4 weeks to <6 months after a platinum-containing therapy. - Endometrial carcinoma: participants must have received ≥1 line of chemotherapy for relapsed or advanced (Stage IV, IIIc) disease. - Cervical carcinoma: participants must have received ≥1 line of chemotherapy for relapsed or advanced (Stage IV b) disease. - Carcinosarcomas (Malignant Mixed Mullerian Tumor) are allowed, but all other nonepithelial cancers of the ovary, fallopian tube, endometrium, or cervix are excluded. - Participants must have either measurable disease per RECIST 1.1 or evaluable disease outside irradiated field on CT/MRI. For ovarian cancer: Participants must have disease that is measurable according to RECIST or assessable according to the Gynecological Cancer Intergroup (GCIG) CA-125 criterion. A rise in CA-125 or other tumor marker alone is not sufficient. Exclusion Criteria: - Disease-Specific Exclusions: - Evidence of complete or partial bowel obstruction. - Need of Total Parenteral Nutrition. - Participants who are pregnant or breast feeding. - Radiation (except planned or on-going palliative radiation to bone outside of the region of measurable disease) ≤3 weeks prior to Cycle 1 Day 1. - Chemotherapy, endocrine therapy, immunotherapy or any other systemic anti-cancer therapy (including investigational anti-cancer therapy) ≤3 weeks prior to Cycle 1 Day 1. - Diagnosis or recurrence of invasive cancer other than the present cancer within 3 years (except basal or squamous cell carcinoma of the skin that has been definitively treated). - Unstable cardiovascular function: - Symptomatic ischemia, or - Uncontrolled clinically significant conduction abnormalities (e.g. ventricular tachycardia on anti-arrhythmics are excluded and 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block (LAFB)/ right bundle branch block (RBBB) will not be excluded), or - Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥3, or myocardial infarction (MI) within 3 months of Cycle 1 Day 1. - Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to the first dose. Active infection with concurrent treatment is acceptable only if the participant is clinically stable. - Significantly diseased or obstructed gastrointestinal tract or uncontrolled vomiting or diarrhea. - Concurrent therapy with approved or investigational anti-cancer therapeutics. - Medical, psychological, or social conditions that may interfere with the participant's participation in the study or evaluation of the study results. - Known brain metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and glucocorticoids. - All non-epithelial cancers of the ovary, fallopian tube, peritoneum, endometrium or cervix as well as neuro-endocrine tumors are excluded. | |
| 72 | NCT02029638 | terminated | slow accrual | 0.44856736063957214 | phase 2 | ['kidney transplantation'] | ["['N26.2', 'Q63.0', 'Q63.2', 'Z52.4', 'I75.81', 'N19', 'N20.0']"] | ['fludarabine', 'cyclophosphamide', 'acetaminophen', 'diphenhydramine', 'methylprednisolone', 'mesna', 'mycophenolate mofetil', 'prednisone', 'filgrastim'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'ClCCN(CCCl)P1(=O)NCCCO1', 'CC1=CC(O)=CC(C)=C1Cl', 'CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1', '[H][C@@]12CC[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C', 'OS(=O)(=O)CCS', 'N[C@@H](CCCNC(N)=N)C(O)=O', '[H][C@@]12CC=C(C3=CC=CN=C3)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: - Recipient participants must meet all of the following criteria to be eligible for this study: - Recipient of a first renal allograft from an Human Leukocyte Antigen (HLA)-haploidentical, living related donor. The donor and recipient must be HLA identical for at least one allele (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype. - Age 18 to 65 years. - Single solid organ recipients (kidney only). - Blood Group System (ABO) compatibility with donor. - Donor-Specific Antibody (DSA) will be assessed by the local laboratory 30 days or less prior to transplant using solid phase micro particle technology (by Luminex® phenotype panel or Luminex single antigen bead test.) The following criteria apply: - Participants without detectable DSA will be deemed eligible if they meet other entry criteria. - Participants with detectable DSA and a positive flow cytometric crossmatch may undergo de-sensitization per standard of care if they are cytotoxic crossmatch negative. Such participants must demonstrate a negative flow cytometric crossmatch by day -9 in order to receive the first dose of study therapy (ATG). Participants who do not demonstrate an acceptable response to de-sensitization by day -9 will be considered screen failures and will be terminated from the study. - Participants with a positive cytotoxicity crossmatch will be excluded. - No known history of anti-HLA antibodies. Recipients with low- level anti-HLA antibodies not considered to be clinically significant may be eligible, following consultation with the Protocol Chairs, the local HLA Laboratory Director, the NIAID Medical Monitor and the ITN Clinical Trial Physician. - Negative T and B cell flow crossmatches with the designated donor; as assessed by local laboratories. If one or more of the crossmatches is positive, the participant will be considered a screen failure unless combined results of antibody and cross match testing implicate a non-HLA antibody as the cause of the positive flow crossmatch. In this case, the Protocol Chair must approve the participant as a screening success after consultation with the local HLA Laboratory Director. - Normal estimated left ventricular ejection fraction and no history of ischemic heart disease requiring revascularization, unless cleared by a cardiologist. - Forced expiratory volume (FEV1) and forced vital capacity (FVC) > 40% of predicted at the screening visit. - Serological evidence of prior Epstein-Barr virus (EBV) infection as documented by positive IgG and negative IgM antibodies against EBV. - For women of childbearing potential, a negative serum or urine pregnancy test with sensitivity less than 50 Milli-International unit (mIU)/m within 72 hours before the start of study medication. - Use of two forms of contraception with less than a 5% failure rate or abstinence by all transplanted participants for 18 months after the first dose of study therapy. For the first 60 days post-transplant, recipients should be encouraged to use non-hormonal contraceptives due to the potential adverse effect of hormones on bone marrow engraftment. - Ability to receive oral medication. - Ability to understand and provide informed consent. - All participants must demonstrate a negative QuantiFERON® (QFT) assay result within 52 weeks of transplant regardless of Purified Protein Derivative (PPD) status. Participants with a positive QFT assay will not be eligible for the study unless they have completed treatment for latent TB and have a negative chest x-ray. QFT testing done within 52 weeks before transplant is acceptable as long as there is documentation of the results. Prior recipients of a Bacillus Calmette-Guérin (BCG) vaccination are not exempt. - Donor participants must meet all of the following criteria to be eligible for this study: - HLA-haploidentical, first-degree relatives or half-siblings of the recipient participant at the allele or allele group. The donor and recipient must be HLA identical for at least one allele (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype. - Age 18 to 65 years. - Creatinine clearance >80 ml/minute as measured from a 24 hour urine collection within 26 weeks of the screening visit. If a serum creatinine drawn at the screening visit is > 20% higher than the serum creatinine drawn at the time of the 24 urine collection, the creatinine clearance must be re-evaluated by a repeat 24 hour urine test. If the new value is ≤80mg/dL the donor will be excluded. - Meets institutional selection criteria for organ and bone marrow donation. - Ability to understand and provide informed consent for all study procedures including kidney transplant and bone marrow harvest. - Serologic evidence of prior EBV infection as documented by positive Immunoglobulin G (IgG) and negative Immunoglobulin M (IgM) antibodies against EBV. Exclusion Criteria: - Recipient subjects who meet any of the following criteria will not be eligible for this study: - Underlying renal disease with a high risk of disease recurrence in the transplanted kidney, including: 1. Focal segmental glomerulosclerosis (FSGS). 2. Type I or II membranoproliferative glomerulonephritis. 3. Hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura. - Clinically important genital/urinary tract dysfunction. - Body mass index (BMI) > 40. - Women who are breastfeeding. - History of cancer within the last 5 years, except for nonmelanoma skin cancer, stage 1 renal cell carcinoma, stage 1 prostate cancers cured by local resection and any curatively treated carcinomas in situ. - History of positive HIV-1 or HIV-2 serologies or nucleic acid test. - Evidence of prior hepatitis B infection as evaluated by hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (anti-HBc IgM and IgG) and Hepatitis B surface antibody (anti-HBsAb). Subjects demonstrating any one of the following will be excluded: - Positive hepatitis B surface antigen (HBsAg) or - Positive anti-HBc IgM. - Positive anti-HBc IgG. - Positive Hepatitis B virus (HBV) Polymerase chain reaction (PCR). - Positive anti-hepatitis C (HCV) antibodies and a positive serum HCV RNA PCR. All positive HCV antibody results must be assessed by an Electroimmunoassay (EIA) assay and confirmed by a quantitative serum HCV RNA assay. Participants with positive HCV antibodies but undetectable serum HCV RNA may be considered for eligibility. Participants with negative anti-HCV antibodies but unexplained liver enzyme abnormalities must undergo a quantitative serum RNA assay to rule out false negative HCV serologies. - History of active Tuberculosis (TB). - Any active, severe local or systemic infection at the screening visit. - Autoimmune disease requiring immunosuppressive drugs for maintenance. - Use of investigational drug, other than the study medications specified by the protocol, within 30 days of transplantation. - Receipt of a live vaccine within 30 days of receipt of study therapy. - The presence of any medical condition that the Investigator deems incompatible with participation in the trial. - Donor subjects who meet any of the following criteria will not be eligible for this study: - History of type I or type II diabetes mellitus. - History of severe cardiovascular disease, defined as New York Heart Association Class III or IV. - History of blood product donation to recipient. - History of positive HIV-1 or HIV-2 serology or nucleic acid test. - Evidence of prior hepatitis B infection. Subjects demonstrating any one of the following will be excluded: - Positive hepatitis B surface antigen (HBsAg) or - Positive anti- hepatitis B core antigen (HBc) IgM. - Positive anti-HBc IgG. - Positive HBV PCR - Positive anti-hepatitis C (HCV) antibodies and a positive serum HCV RNA PCR. All positive HCV antibody results must be assessed by an EIA assay and confirmed by a quantitative serum HCV RNA assay. Participants with positive HCV antibodies but undetectable serum HCV RNA may be considered for eligibility. Participants with negative anti-HCV antibodies but unexplained liver enzyme abnormalities must undergo a quantitative serum RNA assay to rule out false negative HCV serologies. - Autoimmune disease requiring immunosuppressive drugs for maintenance. - The presence of any medical condition that the Investigator deems incompatible with participation in the trial. |
| 73 | NCT02030535 | completed | 0.7144635319709778 | phase 2 | ['pulmonary disease, chronic obstructive'] | ["['J44.9', 'J44.1', 'J44.0']"] | ['olodaterol', 'tiotropium', 'placebo', 'tiotropium', 'olodaterol'] | ['COC1=CC=C(CC(C)(C)NC[C@H](O)C2=C3OCC(=O)NC3=CC(O)=C2)C=C1', '[H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@]12O[C@@]1([H])[C@]1([H])C[C@@]([H])(C[C@@]2([H])[N+]1(C)C)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1', 'COC1=CC=C(CC(C)(C)NC[C@H](O)C2=C3OCC(=O)NC3=CC(O)=C2)C=C1'] | Inclusion criteria: - patients must sign informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions. - Patients must have a diagnosis of COPD and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator (10 to 45 minutes after 400mcg salbutamol) FEV1>30% and < 80% of predicted normal (ECSC, GOLD II - III) and a post-bronchodilator FEV1/FVC <70% at Visit 1 - Male or female patients, 40 years of age or older. - Patients must be current or ex-smokers with a smoking history of more than 10 pack years. - Patients who have never smoked cigarettes must be excluded. - Patients must be able to perform technically acceptable pulmonary function tests according to ATS/ERS guidelines and maintain records in a paper diary - Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI). Exclusion criteria: - Significant disease other than COPD - Clinically relevant abnormal lab values. - History of asthma. - Diagnosis of thyrotoxicosis - Diagnosis of paroxysmal tachycardia - History of myocardial infarction within 1 year of screening visit - Unstable or life-threatening cardiac arrhythmia - Hospitalization for heart failure within the past year - Known active tuberculosis - Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years - History of life-threatening pulmonary obstruction and patients with chronic respiratory failure - History of cystic fibrosis - Clinically evident bronchiectasis - History of significant alcohol or drug abuse - Thoracotomy with pulmonary resection - Patients treated with oral or patch ß-adrenergics - Patients treated with oral corticosteroid medication at unstable doses or at doses in excess of 10mg prednisolone per day or equivalent - Regular use of daytime oxygen therapy for more than one hour per day - Pulmonary rehabilitation program in the six weeks prior to the screening visit or patients currently in a pulmonary rehabilitation program - Investigational drug within one month or six half lives (whichever is greater) prior to screening visit - Known hypersensitivity to ß-adrenergic and/or anticholinergic drugs, BAC, EDTA - Pregnant or nursing women - Women of childbearing potential not using a highly effective method of birth control - Patient who have previously been randomized in this study or are currently participating in another study - Patients who are unable to comply with pulmonary medication restrictions prior to randomization | |
| 74 | NCT02030574 | terminated | the study is being closed to accrual secondary to low accrual and an interest in opening up a different trial. | 0.3746242821216583 | phase 2 | ['invasive bladder cancer', 'bladder cancer'] | ["['D30.3', 'C67.5', 'C67.9', 'C79.11', 'C67.0', 'C67.1', 'D41.4']", "['D30.3', 'C67.5', 'C67.9', 'C79.11', 'C67.0', 'C67.1', 'D41.4']"] | ['gemcitabine and fractionated cisplatin (combination treatment)'] | ['NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F'] | Inclusion Criteria: 1. Pathologically confirmed muscle-invasive urothelial (transitional cell) carcinoma of the bladder or upper genitourinary tract. 2. Stage T2-T4a. Patients may have nodal disease but there must be no evidence of distant metastases and patients must be candidates for radical cystectomy as determined by urologic surgeon (note from/confirmation by surgeon required). 3. No prior systemic therapy for urothelial carcinoma. Prior intravesical therapy is allowed. 4. Patients are determined by their treating oncologist to not be a candidate high dose cisplatin (> 70mg/m2) due to medical comorbidities. 5. Creatinine Clearance (CrCL or eCCr)) > 25 mL/min calculated using the Cockcroft-Gault formula 6. Patients without serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive the protocol treatment of this study with gemcitabine and weekly fractionated cisplatin. 7. Preexisting neuropathy < grade 2. 8. No prior invasive malignancy within the prior two years. However, prior history of non-muscle invasive bladder cancer and patients with an early stage malignancy that is not expected to require treatment in the next 2 years (such as early stage, resected breast cancer, or asymptomatic prostate cancer) are eligible. 9. ECOG performance status 0 or 1. 10. Age ≥ 18 years of age. 11. Not pregnant and not nursing. Women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to beginning of treatment. Post-menopausal women (surgical menopause or lack of menses >12 months) do not need to have a pregnancy test, please document status. 12. Required Initial Laboratory Values: - Neutrophils ≥ 1,000/μl - Platelet count ≥ 100,000/μl - Total bilirubin ≤ 1.5 x ULN. - AST (SGOT) & ALT (SGPT) ≤ 3.0 x ULN Exclusion Criteria: 1. Metastatic disease. 2. Prior hypersensitivity to platinums that in the investigators opinion would put the patient at risk if re-exposed 3. Small cell cancer of the bladder or pure adenocarcinoma. Patients with mixed histologies such as urothelial carcinoma with sarcomatoid features, squamous differentiation or adenocarcinoma are allowed as long as transitional cell cancer is the predominant pathologic subtype. |
| 75 | NCT02030925 | completed | 0.4464731812477112 | phase 2 | ['gastroesophageal reflux'] | ["['K21.9', 'K21.00', 'K21.01']"] | ['iw-3718', 'matching placebo'] | ['CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: - Patient is between 18 and 65 years of age at the Screening Visit; females must not be pregnant or must not be breastfeeding; - Patient has a confirmed diagnosis of gastroesophageal reflux disease, must be currently taking a proton pump inhibitor (PPI), and must be experiencing GERD symptoms as specified by the protocol. Exclusion Criteria: - Patient may not meet any of the excluded conditions specified in the protocol; - Patient is experiencing alarm symptoms such as GI bleeding, anemia, vomiting, dysphagia, or unexpected weight loss; - Patient has a clinically significant hypersensitivity or allergies to any of the active ingredients or excipients in the study medication. | |
| 76 | NCT02031081 | completed | 0.5913560390472412 | phase 2/phase 3 | ['gastroparesis', 'diabetes mellitus'] | ["['K31.84']", "['P70.2', 'O24.92', 'Z83.3', 'E10.65', 'E10.9', 'E11.65', 'E11.9']"] | ['prucalopride', 'placebo'] | ['COCCCN1CCC(CC1)NC(=O)C1=C2OCCC2=C(N)C(Cl)=C1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Age of 18-64 years - Existing clinical diagnosis of gastroparesis for at least one year as judged by the study gastroenterologist based on past medical history, clinical symptoms - Sufficiently symptomatic at time of proposed study (Minimum baseline postprandial satiety/fullness subscale of the Gastroparesis Cardinal Symptoms Index (GCSI) score of 1.5 or higher) - Delayed gastric emptying (>10% retention at 4 hours) on standard solid meal scintigraphic emptying study within the previous year - Normal upper endoscopy (with the exception of small bezoars) since the onset of symptoms - If female of childbearing potential, a negative urine pregnancy test administered between consent and screening appointments - Able to provide written informed consent Exclusion Criteria: - Clinical evidence (including physical exam and/or ECG) of significant cardiovascular, respiratory, renal, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns, including pregnancy or breastfeeding. - Study entry ECG showing second or third degree heart block, left bundle branch block (LBBB) or acute ischemic changes - Blood electrolytes (Na, K, CL) measured within past 6 months outside of normal reference ranges (except during an acute gastroparesis flare-up) - Use of narcotics or promotility agents which cannot be stopped prior to study entry. - Use of tricyclic antidepressants (at doses exceeding 25 mg/day) and/or macrolide antibiotics. (Stable doses of SSRI/SNRI antidepressants and/or non-macrolide antibiotics are permitted) - Laxative use that cannot be stopped prior to the start of the study - Participated in clinical trial with motility agents within past 30 days - History of gastrointestinal surgery excepting appendectomy and/or cholecystectomy in the past, or any other major surgeries within 3 months - Estimated GFR<30 measured within past 6 months. - History of cardiovascular disorder including myocardial infarction, pacemaker or implanted defibrillator, or history of life-threatening arrhythmia | |
| 77 | NCT02031276 | completed | 0.3946417570114136 | phase 2 | ['crohn disease'] | ["['K50.90', 'K50.913', 'K50.914', 'K50.911', 'K50.912', 'K50.918', 'K50.919']"] | ['risankizumab iv', 'risankizumab sc', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion criteria: 1. Men or women 18-75 years at the time of consent. 2. Diagnosis of Crohn's disease (CD) at least 3 months prior to screening. 3. Moderate to severe active CD, defined as Crohn's Disease Activity Index (CDAI) ≥ 220 and ≤ 450. 4. Presence of mucosal ulcers in at least one segment of the ileum or colon and a Crohn's Disease Endoscopic Index of Severity (CDEIS) score ≥ 7 (for patients with isolated ileitis, ≥4), as assessed by ileocolonoscopy and confirmed by central independent reviewer before randomization 5. Patients who are naive or experienced to 1 or more TNF antagonists (infliximab, adalimumab, or certolizumab pegol) at a dose approved for CD. TNF antagonist experienced patients may have stopped anti-TNF treatment due to primary or secondary non-responsiveness, intolerance or for other reasons. 6. Female patients: Women of childbearing potential (not surgically sterilized and between menarche and 1 year postmenopause), that, if sexually active agree to use one of the appropriate medically accepted methods of birth control in addition to the consistent and correct use of a condom from date of screening until 15 weeks after last administration of study medication. Medically accepted methods of contraception are: ethinyl estradiol containing contraceptives, diaphragm with spermicide substance, and intra-uterine-device, or 1. Surgically sterilized female patients with documentation of prior hysterectomy, tubal ligation or complete bilateral oophorectomy, or 2. Postmenopausal women with postmenopausal is defined as permanent cessation = 1 year of previously occurring menses, and 3. Negative serum ß-Human Chorionic Gonadotrophin (ß-HCG) test at screening and urine pregnancy test prior to randomization. Male patients: 1. Who are documented to be sterile, or 2. Who consistently and correctly use effective method of contraception (i.e. condoms) during the study and 15 weeks after last administration of study medication. 7. Have the capacity to understand and sign an informed consent form. 8. Be able to adhere to the study visit schedule and other protocol requirements. Exclusion criteria: 1. Have complications of CD such as strictures, stenoses, short gut syndrome, or any other manifestation that might require surgery, could preclude the use of the CDAI to assess response to therapy, or would possibly confound the evaluation of benefit from treatment with BI 655066. 2. Have any current or prior abscesses, unless they have been drained and treated at least 6 weeks prior to randomization and are not anticipated to require surgery. Patients with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present. 3. Have had any kind of bowel resection or diversion within 6 months or any other intra-abdominal surgery within 3 months prior to screening. Patients with a current ileostomy or colostomy are excluded. 4. Have received treatment with: - Total parenteral nutrition (TPN) within 2 weeks of screening. - Any dose of ustekinumab (Stelara®). - Anti-TNF therapy ≤ 8 weeks prior to the first administration of study medication or any other biologic ≤ 8 weeks prior to the first administration of study drug or within 5 times the half-life of the biologic prior to the first administration of study agent, whichever is longer. - Natalizumab, efalizumab, or agents that deplete B or T cells (e.g., rituximab, alemtuzumab, or visilizumab) within 6 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population. - Any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent prior to the first administration of study agent, whichever is longer. - Regular daily use of opioids for medical reasons within previous 3 months prior to the first administration of study agent. - Rectal 5-aminosalicylic acid (5-ASA) compounds, parenteral or rectal corticosteroids must have been discontinued at least 4 weeks prior to visit 2. - Cannot adhere to the concomitant medication requirements specified in section 4.2.2. 5. Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study, or within 15 weeks after receiving the last dose of study medication. 6. Have used apheresis (e.g., Adacolumn apheresis) ≤ 2 weeks prior to screening. 7. Have received any live bacterial or viral vaccination ≤ 12 weeks prior to Day 1. Patients must agree not to receive a live virus or bacterial vaccination during the study or up to 12 months after the last administration of study drug. 8. Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening. Patient must agree not to receive a BCG vaccination during the study or up to 12 months after the last study drug administration. 9. Have signs or symptoms of infection, history of chronic or recurrent infection, have evidence of active herpes zoster infection ≤ 8 weeks of screening, have a stool culture or other examination positive for an enteric pathogen, have a history of latent or active granulomatous infection, infected with human immunodeficiency virus (HIV), hepatitis B (HepB) or hepatitis C (HepC) virus, established nonserious infections 10. Are not eligible according to tuberculosis (TB) screening criteria 11. Have severe, progressive or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, neurologic, cerebral or psychiatric disease or signs and symptoms. 12. Have a transplanted organ 13. Have known history of lymphoproliferative disease 14. Have any malignancy or history of malignancy 15. Have previously undergone allergy immunotherapy 16. Are unable or unwilling to undergo multiple venipunctures 17. Are known to have substance abuse 18. Are currently or intending to participate in any other study 19. Have screening laboratory test results within the protocol stated parameters 20. Have a known hypersensitivity to study drug 21. Have evidence of current or previous clinically significant disease, medical condition other than CD, finding of the medical examination or lab value. | |
| 78 | NCT02031458 | completed | 0.35342851281166077 | phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['atezolizumab'] | ['CCCNCC(O)COC1=C(C=CC=C1)C(=O)CCC1=CC=CC=C1'] | Inclusion Criteria: - Adult participants greater than or equal to 18 years of age - Locally advanced or metastatic (Stage IIIB, Stage IV, or recurrent) NSCLC - Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens - PD-L1-positive tumor status as determined by an immunohistochemistry (IHC) assay based on PD-L1 expression on tumor infiltrating immune cells and/or tumor cells performed by a central laboratory - Measurable disease, as defined by RECIST version 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: - Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment; the following exception are allowed: Hormone-replacement therapy or oral contraceptives tyrosine-kinase inhibitors (TKIs) approved for treatment of NSCLC discontinued >7 days prior to Cycle 1, Day 1 - Central nervous system (CNS) disease, including treated brain metastases - Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with negligible risk of metastases or death and treated with expected curative outcome - History of autoimmune disease - History of idiopathic pulmonary fibrosis (including pneumonia), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening CT scan. History of radiation pneumonitis in the radiation field (fibrosis) id permitted - Active hepatitis B or hepatitis C - Human Immunodeficiency virus (HIV) positive - Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents | |
| 79 | NCT02031536 | terminated | slow accrual | 0.36238113045692444 | phase 2 | ['gastrinoma', 'glucagonoma', 'insulinoma', 'liver metastases', 'pancreatic polypeptide tumor', 'recurrent islet cell carcinoma', 'somatostatinoma'] | ["['Z52.6', 'K71.8', 'K71.7', 'A06.4', 'C22.0', 'C22.3', 'K70.0']", "['K90.3', 'K86.81', 'Q45.2', 'C25.3', 'E16.9', 'E16.8', 'Q45.3']", "['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['everolimus'] | ['[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: - Patients must have histologically or pathologically confirmed metastatic low or intermediate grade pancreatic neuroendocrine tumor(s) to the liver as per the Klimstra guidelines - Patients must have recovered from an R0 or R1 resection of all disease (including resection of a primary primitive neuroectodermal tumor [PNET] if present); patients may have had resection plus microwave or radiofrequency ablation, provided that no ablated lesion was >= 5 cm prior to ablation - Patients must be within 4 to 8 weeks from the completion of surgery at time of randomization - Patients must have paraffin-embedded fixed metastatic tumor tissue available for submission for central review; core biopsy or surgical specimens required - Patients must have post-operative computed tomography (CT) or magnetic resonance imaging (MRI) prior to randomization and =< 4 weeks after completion of surgery to confirm disease status; patients must be able to tolerate CT or MRI imaging including contrast agents as required for the protocol - Women of child-bearing potential and sexually active males must be strongly advised to use an accepted and highly effective method of contraception or abstain from sexual intercourse for the duration of their treatment through 8 weeks after their last dose of protocol therapy; women of child-bearing potential, sexually active males, and the female partners of male participants should be advised of the risk of becoming pregnant or fathering a child while receiving protocol treatment; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately - Prior treatment with sunitinib and/or cytotoxic chemotherapy are allowed provided last dose was > 30 days prior to randomization - Prior chemoembolization is allowed provided last dose was > 30 days prior to randomization - Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 X institutional ULN - Serum creatinine =< 1.5 X institutional ULN or creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 X institutional normal - Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN - Absolute neutrophil count >= 1,500/mm^3 - Leukocytes >= 3,000/mm^3 - Platelets >= 100,000/mm^3 - Hemoglobin >= 9 g/dL - Patients with a history of the following within =< 12 months of randomization are not eligible - Arterial thromboembolic events - Unstable angina - Myocardial infarction - Patients with known history of abnormal pulmonary function must have documentation of diffusing capacity of the lung for carbon monoxide (DLCO) of > 50% predicted and oxygen saturation (SaO2) of > 87% at rest on room air =< 4 weeks prior to randomization - Patients with unexplained pulmonary infiltrates must have pulmonary function tests within the institutional limits of normal =< 4 weeks prior to randomization - Patients with poorly controlled diabetes mellitus as defined by hemoglobin A1c (HbA1c) > 8% despite adequate therapy are ineligible; patients with a known history of impaired fasting glucose or diabetes mellitus must have blood glucose and antidiabetic treatment monitored closely throughout the trial and adjusted as necessary - Patients may not be receiving any other investigational agents while on study treatment; prior treatment with other investigational agent is allowed provided last dose was >= 30 days prior to randomization - Patients must NOT have received live attenuated vaccines =< 1 week prior to randomization; patients should also be advised not to receive live attenuated vaccines during the study and to avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 - Patients must have life expectancy >= 12 weeks - Patients should be advised to avoid drugs or foods that are known potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors or inducers EXCLUSION CRITERIA: - Patients have received prior everolimus - Patients have either clinically apparent central nervous system metastases or carcinomatous meningitis =< 6 months prior to randomization - Women are pregnant or breast-feeding; all females of childbearing potential must have a blood test within 2 weeks prior to randomization to rule out pregnancy - Patients are on chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed - Patients have history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus - Patients have known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) - Patients have absorption issues that would limit the ability to absorb everolimus - Patients have a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study - Patients have previous or concurrent malignancy; exceptions are made for patients who meet any of the following conditions: - Non-melanoma skin cancer, in situ cervical cancer, breast cancer in situ, or superficial bladder cancer (noninvasive papillary carcinoma or carcinoma in situ); OR - Prior malignancy completely excised or removed and patient has been continuously disease free for > 5 years - Patients have severe and/or uncontrolled medical conditions such as: - Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to randomization, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease - Symptomatic congestive heart failure of New York Heart Association class III or IV - Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and chronic hepatitis (i.e. quantifiable hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA]) - Active, bleeding diathesis - Patients have known history of human immunodeficiency virus (HIV) seropositivity - Patients have experienced thrombotic events (deep vein thrombosis, pulmonary embolism) =< 3 months prior to randomization - Patients have liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis at randomization; patients at increased risk for hepatitis B or hepatitis C must be screened for hepatitis prior to randomization - Patients have ongoing cardiac dysrhythmia of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0) grade >= 2, uncontrolled atrial fibrillation of any grade, or corrected QT (QTc) interval > 470 msec - Patients have history of severely impaired pulmonary function for their age |
| 80 | NCT02033278 | terminated | low recruitment rate, bibliographic evidence of lack of efficacy | 0.5094259977340698 | phase 2 | ['idiopathic dilated cardiomyopathy'] | ["['Q93.81', 'B33.4', 'A36.81', 'A50.54', 'A52.00', 'A52.09', 'B33.24']"] | ['infusion of autologous mononuclear bone marrow cells', 'placebo infusion'] | ['CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: 1. Patients of both sexes and ages between 18 and 70 years. 2. Patients diagnosed with dilated cardiomyopathy established by echocardiography. 3. Minimum evolution since diagnosis of 6 months. 4. Absence of coronary injury tested with multislice CT and/or hemodynamic study performed after study entry, or within the previous 36 months (or before in specific low risk clinical profiles) if no angina symptomatology is present. 5. Patients receiving optimized medical therapy for at least 6 months prior to enrollment (individually adjusted according to functional status). 6. Ejection fraction of the left ventricle <40% or ejection fraction of the left ventricle 40% -50% if left ventricular tele-diastolic volume is > 110 ml/m2. 7. Presence of sinus rhythm. 8. Writen informed consent for participation in the trial. 9. Normal laboratory parameters, defined by: Leukocytes ≥ 3000; Neutrophils ≥ 1500; Platelets ≥ 100,000; Aspartate aminotransferase / Alanine aminotransferase ≤ 2.5 standard range institution; Creatinine ≤ 2.5 mg / dL; Haemoglobin > 9 g/dL 10. Women of childbearing potential must have negative results on a pregnancy test and agree to use medically approved methods of contraception thoughout follow up. Exclusion Criteria: 1. Secondary Dilated cardiomyopathy. 2. Recent history of myocarditis (< 6 months prior to study entry). 3. Patients amenable to receive cardiac resynchronization therapy 4. Patients in active waiting list for heart transplantation. 5. Coexistence of other serious systemic diseases. 6. Coexistence of any type of blood disease 7. Pregnant or breastfeeding women; or women of childbearing potential not comminting to use effective contraception. 8. Patients who are currently participating, or have completed their participation in a clinical trial within the last 3 months. Patients who have participated in any advanced therapies clinical trial any time previously. 9. Patients with malignant or pre-malignant tumors. 10. Positive serology for hepatitis B virus, hepatitis C virus or human immunodeficiency virus. 11. Use of any protocolo prohibited medication. A wash-out period of 2 months can be considered for inclusion in the trial. |
| 81 | NCT02033993 | completed | 0.3738992512226105 | phase 2 | ['urothelial cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['nab-paclitaxel', 'paclitaxel'] | ['[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][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: - Histologically or cytologically confirmed diagnosis of TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) and metastatic or locally advanced inoperable disease extent (T4, N2, N3 or M1 disease) Note: Mixed histologies (except small cell) permitted if predominately TCC by IHC. - Patients must have evidence of metastatic disease, but measurable disease is not mandatory. To be considered evaluable for the overall response rate (complete and partial response), patients must have at least one measurable lesion as follows: - X-ray, physical exam ≥ 20 mm - Conventional CT scan, MRI ≥ 20 mm - Spiral CT scan ≥ 10 mm - Male or female, 18 years of age or older. - ECOG performance status ≤ 2 at study entry - Adequate hematological, renal and hepatic functions as defined by the following required laboratory values obtained within 14 days prior to randomization. If anemic, patients should be asymptomatic and should not be decompensated. - Absolute neutrophil count (ANC) ≥ 1.5 x10^9/L (1,500 cells/mm3) - Platelet count ≥ 90 x10^9/L (100,000/mm3) - Hemoglobin ≥ 90 g/L - Calculated creatinine clearance > 25 mL/min (Cockcroft and Gault formula) - Total bilirubin ≤ 1.5 times the upper limit of normal (≤ 2.5X if Gilbert's disease) - ALT (SGPT) ≤ 3 x ULN or ≤ 5 x ULN if hepatic metastases are present - Patients may have had prior neoadjuvant or adjuvant therapy for completely resected disease, provided it was completed at least 12 months prior to randomization. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments. Neoadjuvant or adjuvant chemotherapy will be considered to have been first line therapy in the metastatic setting if the patient progressed within 12 months of the last dose. - Patients must have received one and only one prior chemotherapeutic regimen which included a platinum (at least one cycle) for metastatic/recurrent disease. Treatment must have been discontinued at least 4 weeks prior to randomization in this study. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments - Patients may not have had any prior therapy with a taxane in any setting. - Patients may have had prior investigational agents but these must have been discontinued at least 4 weeks prior to randomization. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments. - Prior treatments with radiation therapy in the adjuvant and/or metastatic setting are permitted provided that at least 2 weeks have elapsed since the last fraction of radiation therapy and all treatment related adverse events are ≤ Grade 1 at the time of randomization. - Patients may have had prior surgery provided that at least 4 weeks elapsed between the end of surgery and randomization onto the study. Patients must have recovered from any acute toxic effects to ≤ Grade 2 from any prior treatments. - Patients may have peripheral neuropathy from previous treatments providing that it is ≤ Grade 1. - Patient is able (i.e. sufficiently fluent) and willing to complete the health and demographic, quality of life, and health utilities questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to registration/randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible. - Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate. - Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to randomization. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures. - Patients must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. This implies there must be reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on patients being considered for this trial. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, response assessment and follow-up. - In accordance with CCTG policy, protocol treatment is to begin within 5 working days of patient randomization. Exclusion Criteria: - A candidate for potentially curative surgery or radiotherapy. - Patients with brain metastases are ineligible if they meet at least one of the following criteria: 1. diagnosis within 3 months from randomization 2. untreated brain metastases 3. unstable brain metastasis as defined by: - cavitation or hemorrhage in the brain lesion - symptomatic state - daily prednisone or equivalent use greater than 10 mg Patients do not need CT/MRI scans to rule out brain metastases unless there is a clinical suspicion of CNS metastases. - Patients with serious illness or medical condition which would not permit the patient to be managed according to the protocol including, but not limited to: 1. . any evidence of severe or uncontrolled systemic disease (i.e. known cases of hepatitis B or C or human immunodeficiency virus (HIV)). 2. patients with active or uncontrolled infections. Screening for chronic conditions is not required, although patients known to have such conditions at screening should not be included. - Women who are pregnant or breastfeeding. - Patients with history of allergic or hypersensitivity reactions to any study drug or their excipients or with a history of allergic reactions attributed to compounds with similar chemical composition to any of the study drugs. - Planned concomitant participation in another clinical trial of an experimental agent, vaccine or device. Concomitant participation in observational studies is acceptable. - Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years. Prior prostate cancer is allowed provided that it is an incidental finding at cystoprostatectomy with a PSA <0.5 ng/mL at randomization or a prior diagnosis of low risk prostate cancer at any time as defined by ≤T2, a Gleason Score of 6 or less and PSA <10 ng/mL. | |
| 82 | NCT02034071 | completed | 0.5905832648277283 | 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 | |
| 83 | NCT02035124 | withdrawn | study withdrawn due to slow accrual. no patients were enrolled. | 0.409615695476532 | phase 2 | ['advanced prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['bkm 120', 'cabazitaxel'] | ['FC(F)(F)C1=CC(=N)NC=C1C1=CC(=NC(=N1)N1CCOCC1)N1CCOCC1', '[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)OC(C)(C)C)C4=CC=CC=C4)C(C)=C([C@@H](OC)C(=O)[C@]1(C)[C@H](C[C@H]1OC[C@@]21OC(C)=O)OC)C3(C)C'] | Inclusion Criteria: 1. Adenocarcinoma of the prostate confirmed histologically. 2. Metastatic disease confirmed by biopsy or imaging studies. 3. Patients must have received treatment with docetaxel as the only previous chemotherapy regimen. In addition, previous treatment with hormonal agents and/or immune therapy is allowed (e.g., abiraterone). (Previous treatment with MDV3100 will also be allowed.) 4. Patients must be castrate-resistant (i.e. developed progression of metastases following surgical castration or during medical androgen ablation therapy) with documented castrate levels of testosterone (<50 ng/dl). 5. Patients receiving medical castration therapy with gonadotropin-releasing hormone (GnRH) analogues should continue this treatment during this study. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2. 7. Patient must have progressive metastatic prostate cancer by at least 1 of the following criteria: - Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. - Bone scan progression defined by 2 or more new lesions on bone scan. - Prostate specific antigen (PSA) progression is determined by a minimum of three rising PSA levels with an interval of ≥1 week between each determination. The screening PSA measurement (documenting progression) must be ≥2 ng/mL. 8. Screening PSA ≥2 ng/mL. 9. Adequate hematologic, renal and hepatic function: 10. Adequate serum chemistries. 11. Ability to swallow and retain oral medication. 12. Life expectancy of ≥6 months. 13. Patients must be ≥18 years of age. 14. Patients entering this study must be willing to provide tissue from a previous tumor biopsy or 15 unstained slides (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study. 15. Ability to understand the nature of this study and give written informed consent. Exclusion Criteria: 1. Previous treatment with PI3K inhibitors. 2. Known hypersensitivity to BKM120 or polysorbate-80 or any of the excipients or taxanes. 3. Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of BKM120. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of BKM120 is required. 4. Previous chemotherapy with any agent other than docetaxel. All patients must be ≥28 days after their most recent chemotherapy and have recovered from side effects. 5. Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. 6. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 7. Clinical significant peripheral neuropathy (defined as CTCAE v4.0 Grade ≥2) regardless of causality. 8. Mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ≥12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off score of ≥ 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score or the PHQ-9) - anxiety or depression ≥ Grade 3 - medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation, or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified 9. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 28 days (4 weeks) have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases. 10. Leptomeningeal metastases or spinal cord compression due to disease. 11. Acute or chronic liver, renal disease or pancreatitis. 12. Uncontrolled diabetes mellitus. Type II diabetics are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is ≤120. Type I diabetics are eligible if HbAlc is <8. 13. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome). 14. Any of the following cardiac diseases currently or within the last 6 months: - Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) - QTc > 480 ms on screening ECG - Unstable angina pectoris - Congestive heart failure (New York Heart Association [NYHA] ≥ Grade 2 - Acute myocardial infarction - Conduction abnormality not controlled with pacemaker or medication - Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.) - Valvular disease with significant compromise in cardiac function. 15. Family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP). Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or induce TdP and the treatment cannot either be discontinued or switched to a different medication prior to starting study treatment. 16. Inadequately controlled hypertension (i.e., SBP>180 mmHg or DBP>100mmHg). (Patients with values above these levels must have their BP controlled with medication prior to starting treatment) 17. Patient receiving chronic treatment with systemic steroids or another immunosuppressive agent at the start of study treatment. Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. 18. Patients receiving drugs known to be moderate and strong inhibitors or inducers or isoenzyme cytochrome P450 (CYP) 3A (CYP3A) that cannot be discontinued or switched to different medication prior to starting study drug. 19. Patients who have taken herbal medications and certain fruits ≤7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits. 20. Patients currently receiving treatment with therapeutic doses of warfarin sodium. Patients receiving low molecular weight heparin are allowed. 21. A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 22. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV). 23. Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer. 24. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. 25. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol. 26. Fertile male patients, defined as all males physiologically capable of conceiving offspring must use a highly effective contraception during dosing any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after final dosing of study therapy and should not father a child during this period. In addition, female partners of male patients must use a highly effective contraception during dosing of any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after the final dose of study therapy. |
| 84 | NCT02036476 | active, not recruiting | 0.39311128854751587 | phase 2 | ['merkel cell carcinoma', 'skin cancer'] | ["['C79.2', 'C44.500', 'C44.90', 'D23.9', 'D48.5', 'C44.00', 'C44.301']"] | ['cabozantinib'] | ['[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: - Must have histologically or cytologically confirmed Merkel Cell Carcinoma that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques or as ≥10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented - Must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin or another organoplatinum compound. Patients are also eligible if they received curative intent platinum-based therapy and progressed within a year of therapy - No prior MET inhibitor is allowed - At least 2 weeks since prior chemotherapy or radiation therapy. At least 3 weeks since prior biologics or investigational agents - Recovery from effects of recent treatment to baseline or CTCAE ≤ grade 1 toxicity from all prior therapies except alopecia and other non-clinically significant AEs - Participants must be ≥18 years of age - ECOG performance status ≤1 - Participants must have normal organ and marrow function - Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation - Ability to understand and the willingness to sign a written informed consent document - Collection of archival tissue specimens for confirmation of Merkel Cell Carcinoma Exclusion Criteria: - Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier - Participants may not be receiving any biologics or investigational agents within 3 weeks - The subject has active brain metastases or epidural disease - History of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib - Has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 the institutional ULN within 7 days before the first dose of study treatment, unless PT/PTT prolongation known to be secondary to conditions not associated with increased bleeding risk (as on antiphospholipid antibody syndrome) - Requires concomitant treatment, in therapeutic doses, with anticoagulants - Active bleeding or pathologic conditions that carry high risk of bleeding - Have experienced clinically significant gastrointestinal bleeding within 6 months before first dose of study treatment - Requires chronic concomitant treatment of strong CYP3A4 inducers - Is unable or unwilling to swallow tablets - Has a corrected QT interval calculated by the Fridericia formula (QTcF)>500 ms within 28 days before initiation of cabozantinib - Has evidence of tumor invading the GI tract or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib - Has radiographic evidence of cavitating pulmonary lesion(s) - Has uncontrolled, significant intercurrent or recent illness - Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy - History of major surgery within 3 months or minor surgery within 1 month of the first dose of cabozantinib - Pregnant women - Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy - HIV-positive individuals on combination antiretroviral therapy | |
| 85 | NCT02037230 | completed | 0.33315417170524597 | 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. | |
| 86 | NCT02038179 | completed | 0.5736104249954224 | phase 2/phase 3 | ['pre-hypertension', 'jnc 7 stage i hypertension'] | ["['O11.1', 'O11.2', 'O11.3', 'O11.4', 'O11.9', 'O11.5', 'O10.02']", "['I15.0', 'I97.3', 'K76.6', 'P29.2', 'G93.2', 'H40.053', 'I10']"] | ['allopurinol', 'placebo'] | ['O=C1N=CN=C2NNC=C12', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Pre-hypertension or stage I hypertension, defined as the following after the mean of two clinic measurements: - Systolic blood pressure (SBP) ≥ 120 and <160 or; - Diastolic blood pressure (DBP) ≥ 80 and < 100 - Serum urate ≥ 5.0 mg/dL for men or ≥ 4.0 mg/dL for women - Age 18-40 Exclusion Criteria: - Any current pharmacological treatment for hypertension, including diuretics (calcium channel blockers at stable doses were later allowed) - Estimated glomerular filtration rate < 60 mL/min/1.73m2 - Current use of any urate-lowering therapy or statins - Prior diagnosis of gout or past use of urate-lowering therapy for gout - Prior diagnosis of diabetes - Pregnancy, or recent delivery or last trimester pregnancy loss more recent than 3 months - Active smokers - Immune-suppressed individuals including transplant recipients or current use of azathioprine. - Leucopenia with absolute white cell count < 3000 /mL, anemia with hemoglobin < 12 g/dL, or thrombocytopenia with platelet count < 150,000/mL - Individuals of Han Chinese or Thai descent with HLAB5801 genetic phenotype - Serious medical condition that at investigator's judgment precludes utilization of a fixed dose of allopurinol | |
| 87 | NCT02038647 | completed | 0.34866973757743835 | phase 2 | ['small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['alisertib', 'placebo', 'paclitaxel'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[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 Each participant must meet all the following inclusion criteria to be enrolled in the study: 1. Male or female participants ≥ 18 years old. 2. Have a pathologically (histology or cytology) confirmed diagnosis of SCLC. 3. Have received and progressed after a platinum-based standard chemotherapy regimen for first line treatment of SCLC, either limited stage (LS) or extensive stage (ES). 4. Have measurable disease within ≤ 2 weeks before randomization. Clear radiographic evidence of disease progression after initial therapy should have been documented. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (PS 0-1). 6. Participants with treated brain metastases (surgery, whole or stereotactic brain radiation) are allowed provided the lesions have been stable for at least 2 weeks and the participant is off steroids or is on a stable dose of steroids. Participants should be without neurologic dysfunction that would confound the evaluation of neurological and/or other AEs. Exclusion Criteria Participants meeting any of the following exclusion criteria are not to be randomized to treatment: 1. Any prior therapy for second-line treatment of SCLC. 2. Participants who relapsed ≥ 180 days after their response to first-line treatment. 3. Prior treatment with an Aurora A specific-targeted or pan-Aurora-targeted agent, including alisertib, or any other investigational agent. 4. Prior treatment with paclitaxel or any other taxane agent. 5. Known hypersensitivity to Cremophor® EL, paclitaxel, or its components. 6. Any comorbid condition or unresolved toxicity that would preclude administration of alisertib or weekly paclitaxel. 7. Prior history of ≥ Grade 2 neurotoxicity that is not resolved to ≤ Grade 1. 8. Participants with symptomatic and/or progressive brain metastases or with carcinomatous meningitis. 9. Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of alisertib and during study conduct. Major prohibited enzyme inducers include: phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, and St. John's wort. 10. Inability to swallow alisertib or other orally administered medications. 11. Requirement for administration of proton pump inhibitor (PPI), H2 antagonist, or pancreatic enzymes. 12. Diagnosed with or treated for another malignancy within 2 years before the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. 13. Other severe acute or chronic medical or psychiatric condition(s) per protocol. 14. History of myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, any ongoing cardiac arrhythmias of Grade > 2, thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (eg, pericardial effusion or restrictive cardiomyopathy) within 6 months before receiving the first dose of study drug. 15. Known history of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C. 16. Surgery within 3 weeks (or 2 weeks for a minor surgery) before study enrollment and not fully recovered to baseline or to a stable clinical status. 17. Participants who are pregnant, lactating, or do not agree to use effective methods of contraception during the study treatment period through 6 months after the last dose of study drug per protocol. | |
| 88 | NCT02038816 | terminated | accrual too slow, insufficient patients | 0.31661367416381836 | phase 2 | ['myelodysplastic syndromes'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['deferasirox + azacitidine', 'azacitidine'] | ['OC(=O)C1=CC=C(C=C1)N1N=C(N=C1C1=CC=CC=C1O)C1=CC=CC=C1O', 'NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O'] | Inclusion Criteria: - Adults >18 yrs of age - WHO defined MDS with Higher risk MDS (IPSS int-2/high) - Azacitidine X at least 6 cycles with no hematologic improvement/no disease progression as per IWG 2006 criteria - Ferritin >500 µg/L - If transfusion independent, must have Hb <110 g/L OR Neutrophils < 1,000/mL OR Platelets < 100,000/mL - ECOG ≤2 - CrCl >40 ml/min Exclusion Criteria: - Increased ALT (>300 U/L) - Uncontrolled infection - HIV+ - Pregnant or breast-feeding - Previous and concurrent iron chelation - Concurrent use of hematopoietic growth factors including erythropoietin, darbepoietin and granulocyte colony stimulating factor - Concurrent use of other disease modifying agents including cytotoxic chemotherapy, histone deacetylase inhibitors, other hypomethylating agents or lenalidomide |
| 89 | NCT02039947 | completed | 0.3200940489768982 | phase 2 | ['melanoma and brain metastases'] | ["['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']"] | ['dabrafenib', 'trametinib'] | ['CC(C)(C)C1=NC(=C(S1)C1=NC(N)=NC=C1)C1=C(F)C(NS(=O)(=O)C2=C(F)C=CC=C2F)=CC=C1', 'CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1'] | Inclusion Criteria: - ECOG Performance Status range of 0-2 - Histologically confirmed cutaneous metastatic melanoma of V600 E, K, D or R. - May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma. - Must be able to undergo MRI and have at least one measurable intracranial lesion for which specific criteria have to be met. Exclusion Criteria: - Prior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor. - Anti-cancer therapy or investigational anti-cancer therapy or chemotherapy without delayed toxicity within treatment specific timeframe. - Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe. - Any presence of leptomeningeal disease or any parenchymal brain metastasis - History of another malignancy, some exceptions may apply. - A history or evidence of cardiovascular risk- specific criteria have to be met - A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met. | |
| 90 | NCT02040623 | completed | 0.5728868842124939 | phase 2 | ['chronic graft-versus-host disease'] | ["['D89.811', 'D89.812']"] | ['r348 ophthalmic solution, 0.2%', 'r348 ophthalmic solution, 0.5%'] | ['CCC(=O)NS(=O)(=O)C1=CC(NC2=NC=C(F)C(NC3=CC=C(OCC#C)C=C3)=N2)=CC=C1C', 'CCC(=O)NS(=O)(=O)C1=CC(NC2=NC=C(F)C(NC3=CC=C(OCC#C)C=C3)=N2)=CC=C1C'] | Inclusion Criteria: - Received an Allogeneic hematologic stem cell transplantation at least 3 months prior. - Subjects with post Allogeneic hematologic stem cell transplantation onset or worsening of dry eye symptoms for at least 1 month prior. - Use of over-the-counter and/or prescription eye drops for dry eye symptoms within 1 month. - Corneal fluorescein staining score of ≥ 2 in 1 region and ≥ 1 in at least 1 other region. - Total lissamine green conjunctival staining score (according to a modified National Eye Institute grading system) of ≥ 2. Exclusion Criteria: - Clinically unstable Graft versus Host Disease (requiring a change in immunosuppressive regimen), medical condition, or laboratory abnormality - Used topical ophthalmic cyclosporine within 45 days. - Used any topical ophthalmic steroid within 2 weeks. - Used autologous serum eye drops within 2 weeks. | |
| 91 | NCT02040857 | completed | 0.3763408660888672 | phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['palbociclib', 'aromatase inhibitor'] | ['[Na+].CC([O-])=O', 'CC(C)(C#N)C1=CC(=CC(CN2C=NC=N2)=C1)C(C)(C)C#N'] | Inclusion Criteria: - Participants must have histologically confirmed hormone receptor positive (HR+) HER2 negative stage II (except T2N0) or stage III invasive breast cancer. Evaluation for metastatic disease is not required in the absence of symptoms. - Men and both pre- and postmenopausal women are eligible. - Prior Treatment: - Participants may have received (neo)adjuvant chemotherapy, but must be at least 30 days after last dose, with no more than grade 1 residual toxicity at time of screening. - Participants may have received adjuvant radiotherapy, but must be at least 30 days after last dose , with no more than grade 1 residual toxicity at the time of screening. - If most recent therapy was surgery, participants must be at least 30 days out from definitive surgery with no active wound healing complications. - Participants must have demonstrated ability to tolerate endocrine therapy by prior successful completion of at least 1 month of tamoxifen or aromatase inhibitor (AI) therapy without significant adverse events, and in the opinion of the treating physician any ongoing toxicity does not preclude ability to continue on tamoxifen or AI for at least a projected 2 year continuous duration. Ongoing use of any endocrine therapy, including tamoxifen, letrozole, anastrozole, or exemestane, is allowed. Patients may enroll within 2 years of beginning endocrine therapy, as long as there is a plan for at least 2 more years of adjuvant endocrine therapy. - ECOG performance status 0-1 - Age ≥18 years. - Normal organ and marrow function - Baseline QTc ≤ 480 ms - The effects of palbociclib on the developing human fetus are unknown. Women who might become pregnant must use adequate contraception - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Concurrent therapy with other investigational agents. - Prior therapy with any CDK4/6 inhibitor. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib. - Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes are ineligible. - Current use of drugs that are known to prolong the QT interval - Subjects with organ allograft requiring immunosuppression. - 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. Breastfeeding should be discontinued prior to entry onto the study. - Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. - No ongoing combination antiretroviral therapy | |
| 92 | NCT02040870 | completed | 0.35820794105529785 | 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. | |
| 93 | NCT02041260 | active, not recruiting | 0.5047650933265686 | phase 2 | ['differentiated thyroid cancer (dtc)', 'poorly differentiated thyroid cancer'] | ["['C73', 'D34', 'D44.0', 'Z85.850']"] | ['cabozantinib'] | ['[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: - The subject has a histologic or cytologic diagnosis of a DTC tumor (including poorly differentiated thyroid cancer but not anaplastic thyroid cancer) that is metastatic or unresectable and fulfills the following criteria: a. Subjects must have progressive disease as defined by RECIST 1.1 criteria when comparing baseline scans to those obtained within the prior 14 months AND b. Subject must have RAIrefractory disease based on at least one of the following: i. Prior dose of RAI exceeding 600mCi ii.Progression of disease within 18 months following a dose of 100mCi iii. Presence of target lesions as defined by modified RECIST criteria which do not take up RAI. - The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate, within 28 days before the first dose of cabozantinib - The subject is 18 years old on the day of consent. - The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - The subject has organ and marrow function and laboratory values as follows within 4 days prior to the first dose of cabozantinib: a. Absolute neutrophil count (ANC) 1500/mm3without colony stimulating factor support b. Platelets 100,000/mm3 c. Hemoglobin 9 g/dL d.Bilirubin 1.5 the upper limit of normal (ULN). For subjects with known Gilberts disease, bilirubin 3.0mg/dL e. Serum albumin 2.0 g/dl f. Serum creatinine 1.5 ULN or creatinine clearance (CrCl) 50 mL/Page 9 of 16 min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: Male: CrCl(mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) Female: Multiply above result by 0.85 g.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3.0 ULN h. Lipase 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis i. Urine protein/creatinine ratio (UPCR) 1 j. Serum phosphorus, calcium, magnesium and potassium LLN - The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document. - Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s). - Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason. - An archived tumor specimen is available for collection. Exclusion Criteria: - The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy),biologic agents (eg, cytokines or antibodies), or any other anti-cancer systemic therapy (including multi-kinase inhibitors). - Prior treatment with cabozantinib - The subject has received radiation therapy: a. to the thoracic cavity, abdomen or pelvis within 3 months of the first dose of study treatment thathas with ongoing complications or is without complete recovery and healing (CT changes related to radiation treatment which are not clinical significant are allowed). b. to bone or brain metastasis within 14 days of the first dose of study treatment c. to any other site(s) within 28 days of the first dose of study treatment - The subject has received radionuclide treatment within 6 weeks of the first dose of study treatment - The subject has received any other type of investigational agent within 28 days before the first dose of study treatment. - The subject has not recovered to baseline or CTCAE Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs (eg. albumin). - The subject has a primary brain tumor. - The subject has active brain metastases or epidural disease who have not been treated with radiation therapy (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 2 months before starting study treatment. (Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility.) - The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or partial thromboplastin time (PTT) test 1.3 the laboratory ULN within 7 days before the first dose of study treatment. - The subject requires concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (eg, clopidogrel). Low dose aspirin ( 81 mg/day), low-dose warfarin (1mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted. - The subject requires chronic concomitant treatment of strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. Johns Wort). - The subject has experienced any of the following: a. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment b. hemoptysis of 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment c. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment - The subject has radiographic evidence of cavitating pulmonary lesion(s) - The subject has tumor in contact with, invading or encasing any major blood vessels - The subject has evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. - The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. Congestive heart failure (CHF): New York Heart Association (NYHA) Class III (moderate) or Class IV (severe) at the time of screening ii. Concurrent uncontrolled hypertension defined as sustained BP 140 mm Hg systolic, or 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment iii. Any history of congenital long QT syndrome iv. Any of the following within 6 months before the first dose of study treatment: unstable angina pectoris clinically-significant cardiac arrhythmias stroke (including TIA, or other ischemic event) myocardial infarction thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) b. Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. Any of the following within 28 days before the first dose of study treatment intra-abdominal tumor/metastases invading GI mucosa active peptic ulcer disease, inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis malabsorption syndrome ii. Any of the following within 6 months before the first dose of study treatment: abdominal fistula gastrointestinal perforation bowel obstruction or gastric outlet obstruction intra-abdominal abscess.Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months before the first dose of study treatment. c. Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy d. Other clinically significant disorders such as: i. active infection requiring systemic treatment within 28 days before the first dose of study treatment ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment iii. history of organ transplant iv. concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment v. history of major surgery as follows: (1) Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications (2) Minor surgery within 1 months of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications In addition complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery - The subject is unable to swallow tablets - The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) 500 ms within 28 days before randomization. . Note: if initial QTcF is found to be 500 ms, two additional EKGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is 500 ms, the subject meets eligibility in this regard - The subject is pregnant or breastfeeding. - The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation. 21. The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee. | |
| 94 | NCT02042534 | completed | 0.3408784568309784 | phase 2 | ['ischemic stroke', 'transient ischemic attack'] | ["['I25.5', 'H47.013', 'H93.013', 'G45.9', 'H47.011', 'H47.012', 'H47.019']", "['G45.9', 'Z86.73', 'G45.8']"] | ['rivaroxaban', 'warfarin'] | ['ClC1=CC=C(S1)C(=O)NC[C@H]1CN(C(=O)O1)C1=CC=C(C=C1)N1CCOCC1=O', 'S1SSSSSSS1'] | Inclusion Criteria: All of below - Acute ischemic stroke or TIA presumed to be cardioembolic origin (within 5 days from stroke onset) with mild severity: infarct size on DWI less than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere - Atrial fibrillation including paroxysmal atrial fibrillation: atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary). - Age ≥19 years - Informed consent Exclusion Criteria: Any of below - Chronic renal failure (GFR less than 30ml/min) or severe hepatic impairment - Significant hemorrhagic transformation (parenchymal hematoma type I or II by the ECASS definition) - Stroke mechanism of presumed small vessel occlusion: single small subcortical infarct in the perforating artery territory - Large hemispheric or cerebellar infarction; larger than 1/3 of MCA territory, 1/2 of ACA territory, 1/2 of PCA territory, and 1/2 of one cerebellar hemisphere - Mechanical valve requiring warfarin therapy - Active internal bleeding - Prior history of symptomatic intracranial bleeding : patients with asymptomatic bleedings or microbleedings on MRI are eligible for inclusion - Major surgery or major trauma within 30 days that might be associated with increased bleeding risk - Clinically significant gastrointestinal bleeding within 6 months - Intravenous tissue plasminogen activator use or mechanical embolectomy within 48 hours plus 'significant hemorrhagic transformation as described above (exclusion criteria 2)' or 'large hemispheric infarction or cerebellar infarction as described above (exclusion criteria 4)' : patients achieving successful reperfusion without hemorrhage nor large infarction are eligible for enrollment - Severe anemia: hemoglobin <10 g/dL - Bleeding diathesis; thrombocytopenia (<90,000/µL, prolonged PT (INR>1.7) - Sustained uncontrolled hypertension: SBP >180 mmHg or DBP >100 mmHg - Severe devastating illness, such terminal cancer, hepatic failure; therefore, the participants have a life expectancy less than 6 months. - Planned invasive procedure with potential for uncontrolled bleeding, including major surgery | |
| 95 | NCT02042950 | terminated | terminated due to poor accrual | 0.4727557301521301 | phase 2 | ['lymphoma'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['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: 1. Confirmed diagnosis of mantle cell lymphoma. 2. Patients must have relapsed or refractory MCL. 3. Understand and voluntarily sign an IRB-approved informed consent form. 4. Age >/= 18 years at the time of signing the informed consent. 5. Patients must have bi-dimensional measurable disease (bone marrow only involvement is acceptable). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less 7. Serum bilirubin <1.5 mg/dl and Creatinine Clearance >/= 30 mL/min, platelet count >50,000/mm^3 and absolute neutrophil count (ANC) > 1,000/mm^3. [Patients who have bone marrow infiltration by MCL are eligible if their ANC is ≥ 500/mm^3 (growth factor allowed) or their platelet level is equal to or > than 30,000/mm^3.]. AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present. Uric acid within normal limits. 8. Females of childbearing potential (FCBP)* must have a negative serum or urine pregnancy test within 30 days of initiation of therapy. * A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). 9. FCBP must agree to use a highly-effective form of birth control while taking the study drug and for 1 month after the last dose of study drug. Highly-effective forms of birth control include implants, injectables, birth control pills with 2 hormones, some intrauterine devices (IUDs), or having a sterilized partner. The type of birth control used must be discussed with and approved by the attending physician prior to initiation of study drug. 10. Males must agree to use a condom with spermicide every time they have sex during the study and for 3 months after the last dose of study drug. They also must agree to not donate sperm during the study and for 3 months after the last dose of study drug. 11. Patients must be willing to receive transfusions of blood products. Exclusion Criteria: 1. Any serious medical condition including but not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. 2. Pregnant or breast feeding females. 3. Known HIV infection. Patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation 4. All patients with active central nervous system lymphoma. 5. Significant neuropathy (Grades 3 - 4, or Grade 2 with pain) within 14 days prior to enrollment. 6. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib). 7. Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring thoracentesis to ascites requiring paracentesis. 8. Patients with active pulmonary embolism or deep vein thrombosis (diagnosed within 30 days of study enrollment). 9. Patients with symptomatic bradycardia (heart rate < 50 bpm, hypotension, light-headedness, syncope). 10. Use of any standard/experimental anti-lymphoma drug therapy, including steroids, within 3 weeks of initiation of the study or use of any experimental non-drug therapy (e.g. donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the study drug treatment. Prior allogeneic SCT within 16 weeks or autologous SCT within 8 weeks of initiation of therapy. 11. Patients with New York Health Association (NYHA) Class III and IV heart failure, myocardial infarction in the preceding 6 months, and conduction abnormalities, including but not limited to atrial fibrillation, atrioventricular (AV) block block, QT prolongation, sick sinus syndrome, ventricular tachycardia, as these patients may be at greater risk for cardiac complication, per carfilzomib labeling. 12. The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent. Investigator discretion is allowed. 13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment. 14. Patients who have received any previous Carfilzomib treatment. |
| 96 | NCT02044146 | completed | 0.6000328660011292 | phase 2/phase 3 | ['acute coronary syndrome', 'percutaneous coronary intervention'] | ["['I24.0']", "['Y35.312S', 'Y35.313S', 'Y35.412S', 'Y35.413S', 'Y35.812S', 'Y35.813S', 'Y35.92XS']"] | ['ticagrelor, prasugrel, clopidogrel'] | ['CC(=O)OC1=CC2=C(CCN(C2)C(C(=O)C2CC2)C2=CC=CC=C2F)S1'] | Inclusion Criteria: - Patients: age >18 yrs, < 75yrs -> 60 kg ( since March 2015 age >75 and < 60 kg eligible - but prasugrel reduced to 5mg daily if randomized to personalized therapy arm) - NSTEMI undergoing PCI will be eligible Exclusion Criteria: - Patients will be excluded if they have: i) a contra-indication for clopidogrel or prasugrel or ticagrelor (as per monograph), ii) have an intolerance to aspirin, iii) have absolute requirement for ticagrelor or prasugrel (e.g. stent thrombosis, allergic reaction to clopidogrel), iv) requirement for anti-coagulation treatment, v) a history of stroke, TIA or intracranial hemorrhage , vi) a platelet count < 100,000/μl, vii) a known bleeding diathesis, viii) hematocrit <30% or >52%, ix) severe liver dysfunction, x) renal insufficiency (creatinine clearance < 30ml/min), xi) adjuvant therapy with a glycoprotein IIbIIIa inhibitor. | |
| 97 | NCT02044510 | terminated | slow recruitment and small observed effect size | 0.4347902238368988 | phase 2/phase 3 | ['urinary bladder, neurogenic'] | ["['G98.0', 'K59.2', 'M48.061', 'M48.062']"] | ['mirabegron', 'placebo'] | ['NC1=NC(CC(=O)NC2=CC=C(CCNC[C@H](O)C3=CC=CC=C3)C=C2)=CS1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion criteria: - Diagnosis of traumatic or nontraumatic suprasacral spinal cord injury (SCI) or multiple sclerosis (MS, based on a neurologist assessment and/or the McDonald criteria)(28) - Age >18 years - Stable method of bladder management for >3months (either spontaneous or provoked voiding, or intermittent catheterization). - Bothersome urinary symptoms (urinary frequency, urgency, or urgency incontinence based on standard ICS definitions(29)) and completed 3 day voiding diary demonstrating at least 1 episode of non-stress based urinary incontinence over the 72hr period (this may be urgency based incontinence or unaware incontinence). - Patient is able to read and speak English Exclusion criteria: Based on Screening visit history: - Participation in another drug or device study in the 60 days prior to the screening visit. - Previous urologic surgery: Transurethral prostatectomy, bladder augmentation, sphincterotomy, bladder neck sling, artificial urinary sphincter, catheterizable channel, implantable electrostimulator/neuromodulator - Current use of suprapubic catheter/foley catheter - Unstable cardiac disease (uncontrolled hypertension, myocardial infarction, unstable angina, severe congestive heart failure (NYHA 3 or 4), ventricular arrhythmia (such as torsades de pointes), or stroke within the last 6 months) - Clinically significant abnormal ECG - The investigator believes the patient has an increased risk of QT prolongation (based on review of the screening ECG and patients concurrent medications) - History of significant renal dysfunction within 1 year, or serum creatinine >150umol/L at screening visit (visit 1). - History of significant liver disease within 1 year, or serum AST/ALT >2 times upper limit of normal, GGT >3 times upper limit of normal, total bilirubin >2 times upper limit of normal at screening visit (visit 1). - History of pelvic radiation - History of bladder cancer - History of a concurrent malignancy or cancer (except noninvasive skin cancer) within the last 5 years. Subjects with a history of cancer are considered eligible if the subject has undergone potentially curative therapy and the subject has been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin). - Patient has a history of interstitial cystitis/pelvic pain syndrome - Patient has a history of acute or chronic urinary retention within the last 3 months, and is currently not using intermittent catheters - Patient has a history of a tachyarrhythmia - Patient has a history of glaucoma - Patient has a medical condition that may cause noncompliance with the study protocol - In the opinion of the Investigator the patient has a history of significant stress urinary incontinence - Patient has signs and symptoms of an active urinary tract infection (symptoms of dysuria, foul smelling urine, cloudy urine, increased spasticity, increased autonomic dysreflexia, self reported fever, increased incontinence, back/suprapubic pain). o Patient will submit urine for culture and sensitivity, undergo treatment, and will be eligible for rescreening after treatment. - Female patient who is pregnant or breastfeeding, or plans to become pregnant. - Male patient who is planning on fathering a child during the study or for 28 days after the last dose of study drug, or who is planning to donate sperm - Patient refuses to provide written consent - Patient will be unable or unwilling to complete the questionnaires and study visits - In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study. Based on medication and allergy review - The new addition of an anticholinergic medication, or a change to anticholinergic dose, within the last 30 days, (bladder specific anticholinergics include oxybutynin, tolterodine, fesoterodine, solifenacin, darifenacin, trospium, hyoscine, oxybutynin gel or patch, atropine, benzatropine). If previously used and discontinued, these medications must have been stopped for >2 weeks - Newly added bladder active medication (or dose change) within the last 2 months (Tamsulosin, Silodosin, Terazosin, Baclofen, Diazepam, amitriptyline, Finasteride, Dutasteride, DDAVP/desmopressin) - Use of flecainide, propafenone, donepezil, thioridazine, tramadol, aripiprazole, desipramine, imipramine, venlafaxine or digoxin - Intravesical onabotulinum toxin use within the last 1 year - Intravesical oxybutynin within the last 3 months - Patient has a previous history of treatment with mirabegron - Patient has a known allergy to mirabegron or a previous adverse reaction to a beta 3 agonist. Based on physical exam - Patient has a postvoid residual > 250mL at study enrollment after repeated tested (1 attempt to re-void to ensure complete emptying of the bladder) and is not using intermittent catheters - Patient has a resting BP >180 mmHg systolic and/or >110 mmHg diastolic after 2 minutes of sitting quietly - Patient has a resting heart rate >100bpm after 2 minutes of sitting quietly - In the opinion of the study investigator, it is not in the patient's best interest to be enrolled in this study based on a clinically significant abnormality on physical exam. |
| 98 | NCT02044796 | completed | 0.3393862545490265 | 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 | |
| 99 | NCT02044874 | completed | 0.4745524823665619 | phase 2 | ['smoking cessation'] | ["['Y36.881S', 'Y36.891S', 'Y36.880S', 'Y36.881A', 'Y36.881D', 'Y36.890S', 'Y36.891A']"] | ['apd356-lorcaserin hydrochloride', 'placebo'] | ['C[C@H]1CNCCC2=CC=C(Cl)C=C12', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: 1. Males or females aged 18-65 years, inclusive 2. ≥10 cigarettes per day with no period of abstinence longer than 3 months in the past year and who are motivated to quit smoking 3. Able to give signed informed consent 4. Eligible female patients will be: 1. non-pregnant 2. non-lactating 3. agree to use an acceptable method of effective contraception during the study 5. Eligible male patients agree to use contraception when sexually active with a female partner who is not using an acceptable method of birth control 6. Body weight of ≥50 kg (110 pounds), inclusive 7. Considered to be in stable health in the opinion of the investigator Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study. 1. Prior or current use of lorcaserin HCl 2. Prior participation in any study of a nicotine vaccination 3. Use of other therapies for smoking cessation is not allowed within 3 months of screening through study exit 4. Use of tobacco products other than cigarettes 5. Prior use of fenfluramine or dexfenfluramine 6. Serious or unstable medical condition or clinically significant new illness within the 6 months prior to screening 7. Previous participation in any clinical study within 6 weeks prior to the screening visit 8. History of severe allergies, severe drug or excipient allergy or hypersensitivity 9. History of significant cardiovascular condition 10. History of other significant medical conditions 11. Significant risk of suicide 12. Anticipated use of any agents that are associated with valvulopathy and/or pulmonary hypertension 13. Positive test result for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C 14. Recent history of alcohol or drug/solvent abuse 15. Concurrent participation in the study by more than one member of the same household 16. Not suitable to participate in the study in the opinion of the investigator | |
| 100 | NCT02045017 | active, not recruiting | 0.7050086855888367 | phase 2 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['pomalidomide and 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'] | Inclusion Criteria: - Subjects must satisfy the following criteria to be enrolled in the study. 1. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours). 5. Subjects must have had at least 1 prior antimyeloma regimen including lenalidomide and documented progression as per the International Myeloma Working Group uniform response criteria (Durie, 2006) during or after the last antimyeloma regimen. Induction therapy followed by Autologous Stem Cell Transplant and consolidation/ maintenance will be considered as one regimen. 6. Subjects must have an impaired renal function with an estimated Glomerular Filtrate Rate of < 45 mL/min/1.73 m2 according to the modification of diet in renal disease equation. 1. Impaired renal function must be due to multiple myeloma which needs to be confirmed by kidney biopsy. 2. Subjects may have acute myeloma related renal failure or chronic myeloma related renal failure; they may also have been treated with dialysis before, including dialysis with high cut off membranes. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment 1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Renal insufficiency due to other reasons than multiple myeloma or due to hypocalcaemia only. 4. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years; exceptions include the following: 1. Basal or squamous cell carcinoma of the skin 2. Carcinoma in situ of the cervix or breast 3. Incidental histological finding of prostate cancer (Tumour lymphNode Metastasis stage of T1a or T1b) 6. Previous therapy with pomalidomide. 7. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (this includes ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy). 10. Subjects who are planning for or who are eligible for stem cell transplant. |