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| # | nctid | status | why_stop | label | phase | diseases | icdcodes | drugs | smiless | criteria |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | NCT00087451 | completed | 0 | phase 1 | ['malignant glioma', 'glioblastoma', 'gliosarcoma'] | ["['R18.0', 'C17.3', 'G21.0', 'J91.0', 'C05.2', 'C10.0', 'C16.0']"] | ['ap23573'] | ['CO[C@@H]1C[C@H](C[C@@H](C)[C@@H]2CC(=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@@H]3CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@H]3C(=O)O2)OC)CC[C@H]1OP(C)(C)=O'] | Inclusion Criteria (Patients must meet each of the following criteria to be eligible for participation in the trial): - Male or female patients ≥ 18 years of age - Patients must have a radiographically suspected progressive or recurrent primary malignant glioma (glioblastoma multiforme or gliosarcoma) and must have failed standard therapy. Patients may not have received any systemic therapy for the treatment of this recurrence or relapse - Patients must be candidates for surgical resection or open biopsy of the tumor - Patients who have had previous surgical resection(s) are eligible - Patients must have had minimum prior therapy of radiotherapy and documented progression of disease thereafter - Patients must have had a tissue proven malignant glioma - A minimum interval of at least four weeks prior to the first dose of AP23573 must have elapsed for all patients enrolling after either prior surgery or completion of prior external beam radiotherapy for initial primary diagnosis - A minimum interval of four weeks prior to the first dose of AP23573 must have elapsed since receipt of any investigational therapy or any other chemotherapy - Patients in the EIAC cohorts must be presently receiving a stable dose of EIAC (e.g., dilantin, phenytoin, etc.) for at least two weeks prior to the first dose of AP23573 - For patients on corticosteroids, the dose must be stable for at least one week prior to the first dose of AP23573 - Patients must be neurologically stable for at least two weeks prior to the first dose of AP23573 - Patients must have an ECOG performance status of 0 or 1 - Patients must either not be of childbearing potential or have agreed to use a medically effective method of contraception - Patients must have adequate hematologic, renal and liver function as specified in the protocol - Patients must be able to understand and give written informed consent Exclusion Criteria (Patients meeting any of the following criteria are ineligible for participation in the trial): - Women who are pregnant or lactating - Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug formulation - Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin) - Patients with significant cardiovascular disease, as specified in the protocol - Patients with known HIV infection - Patients with any active infection requiring prescribed intervention - Patients receiving immunosuppressive agents other than prescribed corticosteroids - Patients who have had prior therapy with rapamycin, any rapamycin analog or tacrolimus - Patients with inadequate recovery from any prior surgical procedure or patients having undergone any major surgical procedure within two weeks prior to the first dose of AP23573 - Patients with any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug - Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies - Patients with another primary malignancy within the past three years (except for non-melanoma skin cancers and cervical carcinomas in situ) - Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements - Patients are not permitted any chemotherapeutic agents or other antineoplastic agents either during or within four weeks prior to the first dose of AP23573. Additional excluded drugs and treatments are specified in the protocol | |
| 2 | NCT01832766 | terminated | unable to find subjects with schizophrenia that were using only cannabis | 0 | phase 1/phase 2 | ['schizophrenia'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']"] | ['dronabinol'] | ['[H][C@@]12C=C(C)CC[C@@]1([H])C(C)(C)OC1=C2C(O)=CC(CCCCC)=C1'] | Inclusion Criteria: - Male and females - 18 and 50 years of age - Diagnosis of schizophrenia - Chronic cannabis users who have used for at least 1 year - Using cannabis at least once weekly - Currently being treated with antipsychotic medication - Must be on a the same dose of antipsychotic medication for at least 3 months. - Females of childbearing potential must use an adequate form of birth control while participating. - Participants will be required to have blood pressures greater than 90/60 and less than 140/90. Exclusion Criteria: - Use of illicit drugs other than cannabis - Any psychiatric hospitalizations within 3 months - pregnancy in females - taking clozapine |
| 3 | NCT00324623 | completed | 1 | phase 1 | ['melanoma (skin)'] | ["['C43.51', 'C43.9', 'C43.52', 'D03.51', 'C43.8', 'Z85.820', 'D03.52']"] | ['cyclophosphamide', 'fludarabine phosphate'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O'] | DISEASE CHARACTERISTICS: - Diagnosis of metastatic melanoma - Progressive disease after receiving prior Melan-A peptide vaccine on an immunotherapy protocol of the Ludwig Institute AND achieved a detectable immune response (increase of specific CD8^+ TET^+ Melan-A) - Tumor must express MART-1/Melan-A antigen - HLA-A2 positive - Not eligible for other protocols due to progressive disease OR maximum number of vaccine injections with stable disease has been attained PATIENT CHARACTERISTICS: - Performance status 0-2 - Whole blood counts normal - Pulmonary status normal - Transaminases < 1.5 times upper limit of normal (ULN) - Gamma-glutamyl-transferase < 1.5 times ULN - Bilirubin normal - Creatinine clearance > 70 mL/min - No major uncontrolled heart disease - No arterial hypertension PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Prior chemotherapy, biologic therapy, radiotherapy, and/or surgery allowed | |
| 4 | NCT01451632 | completed | 1 | phase 1 | ['colorectal cancer', 'squamous cell head and neck cancer', 'non-small cell lung cancer', 'triple negative breast cancer', 'other tumors with egfr dependence'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['mm-121', 'irinotecan', 'cetuximab'] | ['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: - No standard options remaining - Adequate liver and kidney functions - 18 years of age or above Exclusion Criteria: - History of any secondary active cancer in the last 3 years. - Pregnant or breast feeding - History of severe allergic reactions or contraindications to cetuximab or irinotecan | |
| 5 | NCT00093704 | terminated | study could not recruit any more patients | 0 | phase 1 | ['lymphoma', 'lymphoproliferative disorder'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['D47.Z1']"] | ['bortezomib + ganciclovir'] | ['NC1=NC2=C(N=CN2COC(CO)CO)C(=O)N1'] | Inclusion Criteria: - Histologically confirmed Epstein Barr virus-positive lymphoma, including the following subtypes: - Post-transplantation lymphoma - Burkitt's lymphoma - Hodgkin's lymphoma - T-/NK-cell lymphoma - Unresponsive to, or relapsed after, at least 1 prior chemotherapy regimen - Bidimensionally measurable disease by CT scan - At least 1 lesion ≥ 1.5 cm in the greatest diameter - Age 18 and over - ECOG 0-2 OR - Karnofsky 50-100% - Life expectancy More than 3 months - Hematopoietic - Absolute neutrophil count ≥ 1,000/mm^3 (no growth factor support within the past 4 weeks) - Hemoglobin ≥ 9.0 g/dL - Platelet count ≥ 50,000/mm^3 (no platelet transfusions within the past 4 weeks) - Hepatic - Bilirubin ≤ 2.0 times upper limit of normal (ULN) - AST and ALT ≤ 2.5 times ULN (5 times ULN in patients with liver involvement) - No active hepatitis B or C - Renal - Creatinine clearance ≥ 60 mL/min - Sodium > 130 mmol/L - Negative pregnancy test - Fertile patients must use effective contraception - HIV negative - At least 4 weeks since prior immunotherapy - At least 4 weeks since prior chemotherapy - At least 4 weeks since prior radiotherapy - More than 4 weeks since prior major surgery unless fully recovered - Recovered from all prior therapy - At least 4 weeks since prior investigational agents Exclusion Criteria: - primary or secondary CNS lymphoma or HIV-related lymphoma - known brain metastases - myocardial infarction within the past 6 months - acute ischemia or new conduction system abnormalities by electrocardiogram - symptomatic congestive heart failure - unstable angina pectoris - cardiac arrhythmia - hospitalized - pregnant or nursing - other uncontrolled illness - ongoing or active systemic infection - psychiatric illness or social situation that would preclude study compliance - history of allergic reaction attributable to compounds of similar chemical or biological composition to study drugs - sensitivity to boron, mannitol, bortezomib, or ganciclovir - concurrent corticosteroids (≥ 10 mg of prednisone or equivalent) - concurrent radiotherapy - other concurrent anticancer therapy - other concurrent investigational agents |
| 6 | NCT01291914 | completed | 1 | phase 1/phase 2 | ['osteoarthritis, knee'] | ["['M17.9', 'M17.0', 'M17.10', 'M17.11', 'M17.12', 'M17.2', 'M17.30']"] | ['fx005', 'placebo 1 (carrier)', 'placebo 2 (diluent)'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', '[H][C@]12C[C@@H](O)[C@H](\\C=C\\[C@@H](O)CCCCC)[C@@]1([H])C\\C(O2)=C\\CCCC(O)=O'] | Inclusion Criteria: - Male or female ≥40 years of age - Diagnosis of unilateral or bilateral osteoarthritis of the knee for at least 6 months; confirmation of osteoarthritis according to American College of Rheumatology Criteria (clinical and radiological) - Kellgren-Lawrence grades II or III - Mean score for the WOMAC A subscale (pain) between 2.0 and 3.5 for the index knee - Score of 2-3 for the WOMAC A1 score (pain on walking) for the index knee - Body mass index ≤ 40 kg/m2 - Willingness to abstain from use of restricted medications during the study - Willingness and ability to comply with the study procedures and visit schedule Exclusion Criteria: - Kellgren-Lawrence Grade 0, I or IV radiographic stage of the index knee - Clinically apparent tense effusion in index knee - Presence of surgical hardware or other foreign body in the index knee - Clinical signs and symptoms of active knee infection or crystal disease - Intra-articular corticosteroid within 3 months of Screening - Intra-articular hyaluronic acid within 6 months of Screening - Other intra-articular therapy within 3 months of Screening - Prior arthroscopic or open surgery of the index knee within 12 months of Screening - Planned/anticipated surgery of the index knee during the study period - History of malignancy or other serious, non-malignant, significant, acute or chronic medical (e.g.. uncontrolled diabetes) or active psychiatric illness - Skin breakdown at the knee where the injection would take place - Women who are pregnant, nursing or likely to become pregnant during the time of the study - Women of child-bearing potential (not surgically sterile or post-menopausal for at least 1 year) not using effective contraception | |
| 7 | NCT00565227 | terminated | closed due to toxicity | 0 | phase 1 | ['non-small-cell lung carcinoma', 'prostate cancer', 'bladder cancer', 'urothelial carcinoma'] | ["['D02.20', 'D02.21', 'D02.22']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']", "['D30.3', 'C67.5', 'C67.9', 'C79.11', 'C67.0', 'C67.1', 'D41.4']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['vorinostat (suberoylanilide hydroxamic acid)', 'docetaxel'] | ['ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: 1. There is no limit on prior courses of chemotherapy as long as the regimen did not contain docetaxel. Prior use of paclitaxel (Taxol) or other taxanes is permissible. 2. Only patients with non-small cell lung, prostate, and bladder/urothelial cancer that has progressed after chemotherapy or after hormone therapy. Exclusion Criteria: 1. Patients who have had chemotherapy or radiotherapy within 3 weeks. 2. Patients may not be receiving any other investigational agents nor had prior treatment with histone deacetylase (HDAC) inhibitors (i.e. Valproic acid, PXD-001, Depsipeptide, MS-275 and LAQ-824) 3. Significant cardiovascular disease including congestive heart failure |
| 8 | NCT01259089 | completed | 0 | phase 1/phase 2 | ['adenocarcinoma of the lung', 'non-small cell lung cancer'] | ["['D02.20', 'D02.21', 'D02.22']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['erlotinib hydrochloride', 'hsp90 inhibitor auy922'] | ['COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2', 'CCNC(=O)C1=NOC(=C1C1=CC=C(CN2CCOCC2)C=C1)C1=CC(=C(O)C=C1O)C(C)(C)C'] | Inclusion Criteria: - All patients must have pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically at NU, MSKCC, or DFCI and EITHER previous RECIST-defined response (CR or PR) to an EGFR-TKI (erlotinib or gefitinib) or an investigational EGFR TK inhibitor OR a documented mutation in the EGFR gene (G719X, exon 19 deletion, L858R, L861Q) - Radiographic progression by RECIST during treatment with erlotinib/gefitinib - Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time - Measurable (RECIST) indicator lesion not previously irradiated - Must have undergone a biopsy after the development of acquired resistance - Karnofsky Performance Status >= 70% OR ECOG/WHO Performance Status 0-1 - Signed informed consent - Effective contraception and negative serum pregnancy test obtained within two weeks prior to the first administration of AUY922 in all pre-menopausal women (ie., last menstrual period =< 24 months ago) and women < 2 years after onset of menopause; menopause is defined as the time at which fertility ceases, where a woman has had no menstruation for > 24 months - Total bilirubin =< 1.5 x Upper Limit of Normal (ULN) - AST/SGOT and ALT/SGPT =< 3.0 x ULN, or =< 5.0 x ULN if liver metastasis present - Absolute neutrophil count (ANC) >= 1.5 x10^9/L - Hemoglobin (Hgb) >= 9g/dL - Platelets (plts) >= 100 x 10^9/L - Serum creatinine =< 1.5 x ULN or 24 hour clearance >= 50 mL/min Exclusion Criteria: - Symptomatic CNS metastases which are symptomatic and /or requiring escalating doses of steroids - Prior treatment with any HSP90 inhibitor compounds - Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed) - Palliative radiation within 2 weeks - Unresolved diarrhea >= CTCAE grade 2 - Pregnant or lactating women - Women of childbearing potential (WCBP) (i.e. women able to become pregnant) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile); male patients whose partners are WCBP not using double-barrier methods of contraception - Acute or chronic liver or renal disease - Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol - Major surgery =< 2 weeks prior to randomization or who have not recovered from such therapy - History (or family history) of long QT syndrome - Mean QTc >= 450 msec on baseline ECG - History of clinically manifested ischemic heart disease =< 6 months prior to study start - History of heart failure or left ventricular (LV) dysfunction (LVEF =< 45%) by MUGA or ECG - Clinically significant resting bradycardia (< 50 beats per minute) - Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemi-block (LAHB); ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree AV block - History ventricular tachycardia - Other clinically significant heart disease including congestive heart failure (New York Heart Association class III/IV) or uncontrolled hypertension (> 160/90 despite intensive medical management) - Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 - Known diagnosis of HIV infection (HIV testing is not mandatory) - Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention - Patients who are receiving warfarin (Coumadin®) will be excluded unless =< 2 mg/d, with an INR < 1.5 - Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g. Gilbert's syndrome) | |
| 9 | NCT01448200 | completed | 1 | phase 1 | ['hepatitis c, chronic'] | ["['B18.2', 'B18.0', 'B18.1', 'B18.8', 'B18.9', 'K71.3', 'K71.4']"] | ['ppi-668', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | In order to participate in the study, volunteers for Part I and patients for Part II must meet all of the following key entry criteria, as well as other entry criteria specified in the full protocol: Key Inclusion Criteria 1. Male or female, between 18 and 65 years of age. Female patients must be surgically sterile or two years post-menopausal. 2. Body Mass Index (BMI) 18 - 35 kg/m2 3. In good health, in the judgment of the Principal Investigator 4. Able and willing to comply with all protocol requirements and to sign an informed consent. Key Exclusion Criteria: 1. Seropositive for HIV antibody, or HBV surface antigen (HBsAg) at Screen. Volunteer subjects for Part I must also be negative for HCV antibody. 2. Any medical condition that may interfere with the absorption, distribution or elimination of study drug (PPI-668), or with the clinical and laboratory assessments in this study. 3. Poorly controlled or unstable hypertension; or sustained systolic BP > 150 or diastolic BP > 95 at Screen. 4. History of Diabetes Mellitus treated with insulin or hypoglycemic agents 5. History of alcohol abuse or illicit drug use which, in the investigator's judgment, could interfere with a patient's compliance, with the protocol requirements or with the safety or efficacy assessments of the study 6. History of malignancy unless the malignancy has been in complete remission and without additional medical or surgical interventions during the preceding three years 7. No clinically significant laboratory abnormalities at Screen for healthy volunteers in Part I. For Screen laboratory parameters for HCV patients in Part II, refer to the 'Additional Criteria for HCV Patients' below. Additional Key Entry Criteria for HCV patients (Part II): 1. Clinical diagnosis of chronic hepatitis C, documented by: 1. Clinical findings compatible with chronic hepatitis C, and absence of other known liver disease 2. Seropositive for HCV antibody or HCV RNA at least once previously, and at Screen 3. Serum HCV RNA > 5 log10 IU/mL at Screen, by the PCR assay at the central study laboratory 4. HCV genotype-1 (1a or 1b, or non-subtypable genotype-1), or HCV genotype-2a or genotype-3a 2. ALT must be <5 x ULN at screen 3. No previous treatment with interferon, pegIFN, or ribavirin for genotype-1 patients 4. No history of signs or symptoms of decompensated liver disease 5. Any of the following laboratory values at Screening will be exclusionary for study participation: - Hgb <11 g/dL in women or 12 g/dL in men. - White blood cell count < 4,000/mm3. - Absolute neutrophil count (ANC) < 1800 per mm3. - Platelet count < 100,000 per mm3. - Serum creatinine >ULN at the central study laboratory. - Serum albumin < 3.4 g/dL. - Total bilirubin > 2.0 mg/dL - Clinically significant abnormality in the electrocardiograms (ECGs) at Screen | |
| 10 | NCT00667420 | terminated | closed due to slow accrual | 0 | phase 1/phase 2 | ['esophageal adenocarcinoma', 'gastric adenocarcinoma'] | ["['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']"] | ['panitumumab, epirubicin, oxaliplatin, xeloda'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Patients must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the stomach, gastroesophageal junction, or lower third of the esophagus, AJCC stage II-IIIB (gastric) or IIA-IVA (esophageal). M1a disease will be included, but not T4 lesions. - No prior radiation or chemotherapy including anti-EGFR or vascular endothelial growth factor (VEGF) antibody or tyrosine kinase inhibitor treatments. - All patients must have staging endoscopic ultrasound (EUS) prior to enrollment. - Men or Women >18 years of Age - ECOG performance status <2 (Karnofsky >60%, see Appendix A). - Cardiac ejection fraction >45% by echocardiogram or MUGA scan. - Must be able to either swallow pills or have gastrostomy tube in place for administration of enteral medications. - Patients must have normal organ, metabolic and marrow function as defined below: - Hematologic function, as follows: - Absolute neutrophil count (ANC) ≥ 1.5 x 109/L - Platelet count ≥ 100 x 109/L - Hemoglobin ≥ 9.0 g/dL - Renal function, as follows: - Creatinine < or = 1.5 mg/dL x ULN Hepatic function, as follows: - Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)< or = 3 x ULN - Total bilirubin < 1.5 x ULN Metabolic function, as follows: - Magnesium ≥ lower limit of normal - Calcium < or = lower limit of normal -Human IgG is known to cross the placental barrier; therefore, Panitumumab may be transmitted from the mother to the developing fetus. In women of childbearing potential, appropriate contraceptive measures must be used during treatment with panitumumab and for 6 months following the last dose of panitumumab. If panitumumab is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential risk for loss of the pregnancy or potential hazard to the fetus. 3.1.10 Ability to understand and the willingness to sign and date a written IEC/IRB approved informed consent form. Exclusion Criteria: - Evidence of distant metastatic disease. - T4 tumor on initial staging studies. - History of another primary cancer, except: - Curatively treated in situ cervical cancer - Curatively resected non-melanoma skin cancer - Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ³ 5 years prior to enrollment - Relative or absolute contraindications to surgery which in the opinion of the investigator make the patient a poor candidate for surgical resection. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to panitumumab or other agents used in study. - Subjects requiring chronic use of immunosuppressive agents (e.g., methotrexate, cyclosporine). - 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. - History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or any evidence of interstitial lung disease on baseline chest CT scan. - History of any medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risks associated with the study participation or investigational product(s) administration or may interfere with the interpretation of the results. - Subject unwilling or unable to comply with study requirements. - Women who test positive for serum or urine pregnancy test < 72 hours before randomization or are breast feeding. - Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection. - Major surgery with 28 days or minor surgery within 14 days of study enrollment. - Men or women of child-bearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the course of the study and after the last investigational product(s) administration (24 weeks for women, 4 weeks for men). - Subjects with > grade 1 neuropathy at baseline. - Contraindication to port-a-cath placement. |
| 11 | NCT00156013 | completed | 1 | phase 1/phase 2 | ['lymphoma, b-cell', 'lymphoma, non-hodgkin'] | ["['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']"] | ['clofarabine'] | ['[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: - Adult patients who are at least 18 years old with histology confirmed diffuse large cell B-cell NHL who have failed prior systemic chemotherapy with or without monoclonal antibody-based therapies. - Measurable disease determined by Ct or PET scans or bone marrow involvement, defined as lesions that can be accurately measured in two dimensions by CT or PET scan with the longest diameter accurately as greater than or equal to 1.0 cm or palpable lesions with both diameters greater than or equal to 2.0 cm. PET scan measurable disease is defined based on SUV value as determined by nuclear medicine evaluation. - Eastern Cooperative Oncology Group (ECOG) performance status of 0,1,or 2. - Life expectancy greater than 12 weeks. - Laboratory values obtained less than or equal to 14 days prior to registration: - Absolute neutrophil count (ANC) greater than or equal to 1500. - White blood cell (WBC) count greater than 3.0. - Platelets greater than or equal to 100. - Hemoglobin (HG) greater than 9.0 g/dL. - Total bilirubin less than or equal to 2.0 mg/dL. - Aspartate transaminase (AST)/alanine transaminase (ALT) less than or equal to 3 times the upper limit of normal (ULN). Higher values are acceptable if it is deemed that they are related to liver involvement with NHL. - Serum creatinine less than or equal to 2.0 mg/dL. - Cardiac function on pretreatment MUGA scan or echocardiogram that is considered normal by institutional standards. - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. - Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. - Male and female patients must use an effective contraceptive method during the study and for a minium of 6 months after study treatment. Exclusion Criteria: - Previously untreated NHL. - Received previous treatment with clofarabine. - History of T-cell lymphoma. - Bulky disease (ie, any single mass greater than 10 cm or circulating malignant cells greater than or equal to 24,000 cells/ul. - Patients with known AIDS-related or HIV-positive lymphoma. - Autologous bone marrow or stem cell transplant within 3 months of study entry. - History of allogeneic bone marrow transplant or organ transplant. - Prior radiotherapy to the only site of measurable disease. - Any medical condition that requires chronic use of oral high-dose corticosteroids. ( in excess of 1 mg/kg/day). - Autoimmune thrombocytopenia. - Use if investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy. - Patients with an active, uncontrolled systemic infection considered to be opportunistic, life threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients of parenteral antifungal therapy). - HIV-positive status. - Active secondary malignancy. - Pregnant or lactating patients. - Any significant concurrent disease, illness , or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow-up, or interpretation of study results. - Patients with active or untreated central nervous lymphoma (CNS) lymphoma. | |
| 12 | NCT00551122 | unknown status | 1 | phase 1/phase 2 | ['brain and central nervous system tumors', 'extragonadal germ cell tumor', 'ovarian cancer', 'testicular germ cell tumor'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['E29.0', 'E29.1', 'E29.8', 'E29.9', 'E89.5', 'N50.811', 'N50.812']"] | ['cisplatin', 'gemcitabine hydrochloride', 'ifosfamide', 'paclitaxel'] | ['[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', 'NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F', 'N[C@@H](CCCNC(N)=N)C(O)=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'] | DISEASE CHARACTERISTICS: - Meets the following criteria: - Histologically confirmed extracranial primary germ cell cancer, seminoma, or nonseminoma - Unresectable metastatic disease - No completely resected cancer - Rising serum markers (i.e., alpha-fetoprotein and human chorionic gonadotropin) on sequential measurement or biopsy-proven unresectable germ cell cancer - In first relapse after a single prior cisplatin-containing combination chemotherapy - Patients with late relapse (i.e., > 2 years post initial chemotherapy) should be considered for surgery rather than chemotherapy, if technically feasible - No patients with cerebral metastases alone - Progressive cerebral and systemic disease may be considered for this study, provided cranial irradiation is also considered as a component of care PATIENT CHARACTERISTICS: - Medically and psychologically fit to receive this intensive chemotherapy schedule - WBC > 3.5 times 10^9/L - Platelet count > 130 times 10^9/L - Glomerular filtration rate ≥ 50 mL/min (as determined by 24 hour creatinine clearance or nuclear medicine technique) - Fertile patients must use effective contraception - No other prior malignancy except successfully treated nonmelanoma skin cancer or superficial bladder cancer - No prior allergic reactions to cisplatin or other platinum compounds PRIOR CONCURRENT THERAPY: - See Disease Characteristics | |
| 13 | NCT00903006 | terminated | low accrual | 0 | phase 1/phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['fulvestrant', 'mk-0646', 'dasatinib'] | ['[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]', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1'] | Inclusion Criteria: 1. For the Phase I: Patients with histologically or cytologically confirmed diagnosis of metastatic hormone receptor-positive HER2-negative breast cancer who have received up to one line of endocrine therapy for metastatic disease. 2. Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease) 3. Age >/= 18 years 4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2 5. Required laboratory values: Absolute neutrophil count (ANC)>/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L; bilirubin </= 1.5 * upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN; serum creatinine </= 2.0 * ULN 6. Ability to understand the requirements of the study, provided written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments. 7. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy). 8. Patients must have received prior anti-estrogen therapy in the adjuvant setting. 9. Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology). 10. Patients must consent to biopsies. 11. For the Phase II: Patients with histologically or cytologically confirmed diagnosis of metastatic hormone receptor-positive, HER2-negative, breast cancer who have received up to one line of endocrine therapy for metastatic disease. 12. Measurable disease by RECIST or evaluable disease (e.g., bone metastasis, or lesions which do not fulfill RECIST criteria for metastatic disease) 13. Age >/= 18 years 14. ECOG performance status of </= 2 15. Required Laboratory Values: ANC >/= 1500 cells/mm^3, platelet count >/= 100,000 cells/mm^3, hemoglobin >/= 9 gm/L, Bilirubin </= 1.5 * ULN, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 2.5 * ULN 16. Serum creatinine </= 2.0 * ULN 17. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments. 18. Patients must be postmenopausal (> 12 months of amenorrhea, bilateral oophorectomy). 19. Patients must have received prior anti-estrogen therapy in the adjuvant setting. 20. Patients may have easily accessible tumors for biopsy (confirmed by interventional radiology). 21. Patients must consent to biopsies. Exclusion Criteria: 1. For the Phase I: History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix 2. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, ongoing or recent gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet function abnormality). 3. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy. 4. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2 diabetes mellitus. 5. Active or untreated brain metastasis 6. Pleural or pericardial effusion of any grade 7. Bone only metastases 8. Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease). 9. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed). 10. For the Phase II: History of prior malignancies within the past 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix 11. Concurrent severe or uncontrolled medical disease (i.e., systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure, ongoing or recent gastrointestinal bleed, hepatic or cardiac compromise, hypocalcemia, or known platelet function abnormality). 12. Concomitant medication known to prolong QT interval, unless discontinued >/= 7 days of starting dasatinib therapy. 13. Newly diagnosed (within 3 months before enrollment) or poorly controlled (defined as a fasting serum glucose > 160 mg/dl or hemoglobin A1c > 8% at screening), type 1 or 2 diabetes mellitus. 14. Active or untreated brain metastasis 15. Pleural or pericardial effusion of any grade 16. Bone only metastases 17. Patients for whom endocrine therapy is not appropriate (i.e. life threatening metastatic disease). 18. Patients requiring therapeutic anticoagulation (Warfarin 1 mg for port maintenance is allowed). |
| 14 | NCT01298401 | completed | 0 | phase 1 | ['pancreatic cancer'] | ["['C25.3']"] | ['capecitabine', 'gemcitabine hydrochloride'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F'] | DISEASE CHARACTERISTICS: - Pathologically confirmed (histologic or cytologic) locally advanced adenocarcinoma of the pancreas - Patients must have unresectable disease based on institutional standardized criteria of unresectability or medical inoperability - Patients with or without regional adenopathy are eligible - No distant metastases based upon the following minimum diagnostic workup: - History and/or physical examination, including collection of weight and vital signs, within 28 days prior to study entry - Abdominal and/or pelvic CT scan with IV contrast or MRI scan within 21 days prior to study entry - Chest CT scan or whole-body PET/CT within 21 days prior to study entry - No second malignancy or peritoneal seeding PATIENT CHARACTERISTICS: - Zubrod performance status 0-1 - Absolute neutrophil count (ANC) ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin (Hgb) ≥ 10.0 g/dL (the use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dL is acceptable) - Glycosylated hemoglobin (HgbA1c) ≤ 8% - Serum creatinine ≤ 1.5 mg/dL - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 times upper limit of normal (ULN) - Total bilirubin < 3.0 mg/dL - Alkaline phosphatase < 3 times ULN - Fasting blood glucose < 160 mg/dL - Patients with a non-fasting blood glucose > 160 mg/dL (8.9 mmol/L) must have a fasting blood glucose ≤ 160 mg/dL (8.9 mmol/L) in order to be eligible - No grade 2 or worse hearing impairment - Negative serum pregnancy test (if applicable) - Women of childbearing potential and men who are sexually active must be willing/able to use medically acceptable forms of contraception during the course of the study, and for 3 months (6 months for men) after the last study drug administration - Not pregnant or nursing - Ability to swallow oral medications - At least 3 years since prior malignancy except non-melanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix - No severe active co-morbidity, defined as any of the following: - Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months - Transmural myocardial infarction within 6 months prior to study entry - Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization, or precluding study therapy within 30 days before registration - Uncontrolled malabsorption syndrome significantly affecting gastrointestinal function - Any unresolved bowel or bile duct obstruction - Major resection of the stomach or small bowel that could affect the absorption of capecitabine - Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition - HIV testing is not required for entry into this protocol - Existing venous thromboembolism requiring anti-coagulation therapy - No prior allergic reaction to capecitabine or gemcitabine hydrochloride PRIOR CONCURRENT THERAPY: - No prior systemic chemotherapy for pancreatic cancer - Prior chemotherapy for malignancies other than pancreatic cancer is allowed provided chemotherapy was completed > 3 years prior to study entry - No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields - More than 28 days since any prior major surgery - Insertion of a vascular access device, insertion of a biliary stent, exploratory laparotomy, or laparoscopy are not considered major surgery - No prior ganitumab - Patients requiring concurrent oral anticoagulants (e.g., Coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring international normalized ratio (INR) - No concurrent participation in another clinical treatment trial - No concurrent intensity-modulated radiotherapy - No other concurrent therapy including the following: - Other investigational or approved chemotherapeutic agents - Other monoclonal antibody - Sorivudine or brivudine A - Cimetidine - G-CSF agents | |
| 15 | NCT00621725 | completed | 0 | phase 1 | ['advanced cancer', 'hepatic impairment'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']", "['Z73.82', 'G31.84', 'M10.38', 'M10.30', 'M10.311', 'M10.312', 'M10.319']"] | ['azd2171'] | ['COC1=CC2=C(C=C1OCCCN1CCCC1)N=CN=C2OC1=C(F)C2=C(NC(C)=C2)C=C1'] | Inclusion Criteria: - Written informed consent - Advanced solid tumour (not prostate cancer) for which no standard therapy exists - WHO performance status 0-2 - Bilirubin levels within the target range Exclusion Criteria: - Unstable brain/meningeal metastases - Inadequate bone marrow reserve - Biochemistry/haematology results outside of required ranges - History of significant GI impairment | |
| 16 | NCT01942382 | completed | 0 | phase 1 | ['schizophrenia'] | ["['F20.0', 'F20.1', 'F20.2', 'F20.3', 'F20.5', 'F20.89', 'F20.9']"] | ['paliperidone palmitate'] | ['CC1=C(CCN2CCC(CC2)C2=NOC3=C2C=CC(F)=C3)C(=O)N2CCCC(O)C2=N1'] | Inclusion Criteria:- Participants had to have the capability to provide informed consent in writing to participate in the study - Participants with a diagnosis of schizophrenia in accordance with the diagnostic criteria for Diagnostic and Statistical Manual of Mental Disorders -IV-TR (DSM-IV-TR) - Participants whose psychiatric symptom is considered stable by the investigator/subinvestigator at the time of giving informed consent - Participants with a Positive and Negative Syndrome Scale (PANSS) score of less than or equal to 4 (moderate) in the following 9 items at screening: delusion, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility, uncooperativeness, poor impulse control - Participants with an experience of taking a risperidone formulation or a paliperidone formulation by 8 days before the initial day (Day 1) of the study treatment Exclusion Criteria:- DSM-IV-TR diagnosis other than schizophrenia - DSM-IV-TR diagnosis of substance-related disorders within 180 days before the date of screening - At a risk of suicide or other-injurious behavior as considered by the investigator/subinvestigator , and participants with a history of suicide attempts - Concurrent condition of Parkinson's disease (except for drug-induced extrapyramidal syndrome) - Concurrent condition or history of symptomatic cerebrovascular accident | |
| 17 | NCT01050764 | terminated | safety | 0 | phase 1/phase 2 | ['leukemia, acute', 'chronic myelogenous leukemia (cml)', 'myelodysplastic syndrome (mds)', 'non-hodgkin lymphoma (nhl)', 'chronic lymphocytic leukemia (cll)', 'acute myelogenous leukemia (aml)', 'acute lymphoblastic leukemia (all)'] | ["['D46.Z', 'D46.9', 'C94.6', 'D46.C']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['A87.2', 'K52.832', 'D72.111', 'C91.11', 'C91.12', 'C91.10']"] | ['regulatory t-cells', 'conventional t-cells', 'melphalan', 'thiotepa', 'anti-thymocyte globulin, rabbit', 'clinimacs cd34 reagent system'] | ['[H][C@]12SCC(CSC3=NN=C(C)S3)=C(N1C(=O)[C@H]2NC(=O)CN1C=NN=N1)C(O)=O', 'N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O', 'CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1'] | Inclusion Criteria RECIPIENT - Histopathologically-confirmed: - Acute leukemia (in first remission with poor risk factors and molecular prognosis) - Acute myelogenous leukemia (AML) with -5,-7, t (6;9), tri8, -11 - Acute lymphoblastic leukemia (ALL) with Ph+ t (9;22), t (4;22), (q34;q11) - Acute leukemia with refractory disease or > Complete Remission (CR) 1 - Chronic myelogenous leukemia (CML) (accelerated, blast or second chronic phase) - Myelodysplastic syndrome (in high and high intermediate risk categories) - Non-Hodgkin's lymphoma (NHL) with poor risk features and not suitable for autologous transplantation - Refractory Chronic lymphocytic leukemia (CLL) - At least 21 days from the end of most recent prior therapy to start of the transplant conditioning regimen - Must be < 60 years old at time of registration. - Karnofsky Performance Status (KPS) > 70% Must have related donor who is: - Genotypically human leukocyte antigen (HLA) -A, B,C and DR beta 1 (DRB1), DQ loci haploidentical to the recipient (but differing for 2 to 3 HLA alleles on the unshared haplotype in the graft-versus-host disease (GvHD) direction) - No HLA-matched sibling or matched-unrelated donor is identified. - Adequate cardiac and pulmonary function (left ventricular ejection fraction (LVEF) > 45%, diffusing capacity of the lungs for carbon monoxide (DLCO) >50% corrected for hemoglobin) - Serum creatinine < 1.5 mg/dL OR Creatinine clearance > 50 mL/min for those above serum creatinine at least 1.5 mg/dL - Serum bilirubin < 2.0 mg/dL - Alanine transaminase (ALT) < 2x upper normal limit (ULN) (unless secondary to disease) - No prior myeloablative therapy or hematopoietic cell transplantation DONOR: - Age ≤ 70 years - Weight ≥ 25 kg. - Medical history and physical examination confirm good health status as defined by institutional standards - Seronegative for HIV Ag within 30 days of apheresis collection for: - Hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR) + - Hepatitis C ab or PCR+ - Genotypically haploidentical as determined by HLA typing - Female donors (child-bearing potential) must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within 3 weeks of mobilization - Capable of undergoing leukapheresis - Has adequate venous access - Willing to undergo insertion of a central catheter if leukapheresis via peripheral vein is inadequate - Capable of agreeing to second donation of peripheral blood progenitor cell (PBPC) (or a bone marrow harvest) should the patient fail to demonstrate sustained engraftment following the transplant - Institutional review board (IRB)-approved consent form signed by donor or legal guardian > 18 years of age Donor Selection in the priority order: - Recipient's biological mother preferred, if available - Other available haploidentical donors will be selected based upon the presence of natural killer (NK) alloreactivity between donor and recipient by high-resolution HLA typing of the C locus. An NK-alloreactive donor will be preferentially chosen. Recipients lacking a killer immunoglobulin-like receptor (KIR)-ligand present in the donor along with the corresponding KIR defines "NK alloreactivity". - If more than one NK-alloreactive donor is available, preference is to cytomegalovirus (CMV)-seronegative donor Exclusion Criteria RECIPIENT: - Suitable candidate for autologous transplantation or allogeneic transplantation with an available matched-related or matched-unrelated donor - Seropositive for: - HIV ab - Hepatitis B sAg or PCR+ - Hepatitis C ab or PCR+ - History of invasive Aspergillosis - Any active, uncontrolled bacterial, viral or fungal infection - Uncontrolled central nervous system (CNS) disease involvement - Lactating female DONOR: - Evidence of active infection or viral hepatitis - Factors of increased risk for complications from leukapheresis or granulocyte-colony stimulating factor (G-CSF) therapy - Lactating female - HIV-positive |
| 18 | NCT00374985 | completed | 1 | phase 1/phase 2 | ['esophageal neoplasms', 'stomach neoplasms'] | ["['K22.2', 'K22.81', 'Q39.4', 'P78.83', 'I85.00', 'I85.01', 'I85.10']", "['D13.1', 'C16.9', 'C16.1', 'C16.2', 'D37.1', 'C16.8', 'C16.5']"] | ['docetaxel, oxaliplatin'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - adenocarcinoma of gastric-esophagal junction - stage II to III - unidimensional measurable disease Exclusion Criteria: - surgery of primary tumor - metastasis - prior chemo- or radiotherapy | |
| 19 | NCT00350844 | terminated | low subject accrual | 0 | phase 1/phase 2 | ['sickle cell disease', 'pulmonary hypertension'] | ["['D57.1', 'D57.20', 'D57.212', 'D57.219', 'D57.211', 'D57.213', 'D57.218']", "['I27.0', 'I27.20', 'I27.21', 'I27.24', 'I27.29', 'P29.30', 'I27.22']"] | ['hydroxyurea'] | ['NC(=O)NO'] | Inclusion Criteria: - Age between 10 and 25 years old - Sickle cell disease with hemoglobin SS, SC or S-B^0 thalassemia confirmed on hemoglobin electrophoresis - Tricuspid regurgitant jet velocity (TRJV) equal to or greater than 2.5 m/sec on 2 baseline Doppler echocardiograms at least 3 months apart Exclusion Criteria: - Patients already being treated with hydroxyurea - Patients on a chronic transfusion protocol - Patients with evidence of hepatic (alanine aminotransferase [ALT] equal to or greater than 2 SD above normal) or renal dysfunction (creatinine [Cr] equal to or greater than 2 SD above normal) - Patients who are pregnant - Patients with documented causes of severe pulmonary hypertension other than from SCD |
| 20 | NCT01682902 | completed | 1 | phase 1 | ['diabetes', 'diabetes mellitus, type 1'] | ["['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']"] | ['faster-acting insulin aspart', 'faster-acting insulin aspart', 'insulin aspart'] | ['[Na+].[Na+].[O-]P([O-])(F)=O', '[Na+].[Na+].[O-]P([O-])(F)=O', '[Na+].[Na+].[O-]P([O-])(F)=O'] | Inclusion Criteria: - Type 1 diabetes mellitus (diagnosed clinically) for at least 12 months prior to the screening visit (Visit 1) - Treatment with the same insulin analogue by CSII (continuous subcutaneous insulin infusion) for the previous 3 months prior to the screening visit (Visit 1) - Using a MiniMed Paradigm® pump (515/715, 522/722 or 523/723) for the previous 6 months prior to the screening visit (Visit 1) - Glycosylated haemoglobin (HbA1c) below or equal to 9.0% by central laboratory - Body Mass Index (BMI) below or equal to 35.0 kg/m^2 Exclusion Criteria: - History of diabetic ketoacidsosis (DKA) episodes requiring hospitalization within 6 months prior to the screening visit (Visit 1) - History of abscess at the infusion site within 6 months prior to the screening visit (Visit 1) - Hypoglycaemic unawareness as judged by the Investigator or history of severe hypoglycaemic episodes requiring hospitalization within the last 6 months prior to the screening visit (Visit 1) | |
| 21 | NCT01131364 | terminated | 1 | phase 1/phase 2 | ['advanced solid tumor', 'breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['f16il2 in combination with doxorubicin'] | ['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: • For Phase I of the study: - For patient of Phase I cohort 1 i.e. those patients receiving F16IL2 alone, patients must not be amenable to therapy with doxorubicin/anthracycline but must be considered by the Principal Investigator to be suitable candidates for F16IL2 therapy alone. - Histologically or cytologically confirmed solid cancer with/without evidence of locally advanced or metastatic disease (Appendix B). - For advanced solid cancer patients, patients may have received previous chemotherapy or radiation therapy, but they must be amenable for doxorubicin treatment according to the discretion of the principal investigator. For Phase II of the study: - Histologically or cytologically confirmed breast cancer. - Previous anthracycline therapy, including liposomal doxorubicin, for metastatic and/or adjuvant disease is allowed. However, patients must not have received a cumulative anthracycline dose of more than 300 mg/m2 of doxorubicin or of more than 600 mg/m2 of epirubicin or pegylated or non-pegylated liposomal doxorubicin, prior to study entry, in order to avoid anthracycline-associated cardiotoxicity. - Prior radiation therapy is allowed, if the irradiated area is not the only source of measurable or assessable disease. - Patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease). • For phase I and II of the study: - Patients aged ≥18 years. - Patients recruited to Phase I, cohort I must be considered not suitable to doxorubicin/anthracycline therapy in the opinion of the Principal Investigator. - Only for phase I, patients must not have received more than 300 mg/m2 of doxorubicin or 500 mg/m2 of epirubicin in prior chemotherapy. - Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section APPENDIX A). This lesion must not have been irradiated during previous treatments. - All acute toxic effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) Grade ≤ 1. - Sufficient hematologic, liver and renal function: - Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelets ≥ 100 x 10^9/L, haemoglobin (Hb) ≥ 9.5 g/dl. - Alkaline phosphatase (AP), alanine aminotransferase (ALT) and or aspartate aminotransferase ≥ 3 x upper limit of reference range (ULN), and total bilirubin ≥ 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels could be up to 5 x ULN. - Creatinine ≥ 1.5 ULN or 24 h creatinine clearance ≤ 50 mL/min. - Life expectancy of at least 12 weeks. - Documented negative test for human immunodeficiency virus. - Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment. - If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug. - Evidence of a personally signed and dated Ethics Committee-approved Informed Consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study. - Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria: - Presence of active infections (e.g. requiring antibiotic therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. - Presence of known brain metastases. However, presence of controlled brain metastases (i.e., evaluated as SD of PR after radiotherapy) is allowed. - Known to have a second uncontrolled cancer of other primary origin within the last 5 years. - Chronic active hepatitis or active autoimmune diseases. - History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. - Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). - Irreversible cardiac arrhythmias requiring permanent medication. - LVEF ≤ 50% and/or abnormalities observed during baseline MUGA, ECHO or ECG investigations. - Uncontrolled hypertension. - Ischemic peripheral vascular disease (Grade IIb-IV). - Severe rheumatoid arthritis. - Severe diabetic retinopathy. - Recovery from major trauma including surgery within 4 weeks of administration of study treatment. - Known history of allergy to IL-2, doxorubicin, or other intravenously administered human proteins/peptides/antibodies. - Pregnancy or breast feeding. Female patient must agree to use effective contraception, or be surgically sterile or postmenopausal. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. - Phase I: Chemotherapy (standard or experimental) or radiation therapy within 4 weeks of the administration of study treatment. - Phase II: - Chemotherapy (standard or experimental) within 4 weeks of the administration of study treatment. - Radiation therapy within 6 weeks of the administration of study treatment. - Cumulative exposure to anthracycline-containing chemotherapy prior to study entry precluding the application of at least an additional 150 mg/m2 doxorubicin (total dose for 2 cycles of study therapy). - Treatment with an investigational study drug within 6 weeks before beginning of treatment with F16-IL2. - Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment. - Growth factors or immunomodulatory agents within 7 days of the administration of study treatment. - Neuropathy > Grade 1 - Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion. - Any conditions that in the opinion of the investigator could hamper compliance with the study protocol. | |
| 22 | NCT01027676 | unknown status | 1 | phase 1/phase 2 | ['non-small-cell lung carcinoma'] | ["['D02.20', 'D02.21', 'D02.22']"] | ['study treatment'] | ['COC1=CC=CC=C1OC1=C(NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)N=C(N=C1OCCO)C1=NC=CC=N1'] | Inclusion Criteria: - Histologic or cytologic diagnosis of NSCLC, Stage IV or selected stage IIIB (with positive pleural effusion or multiple ipsilateral lung nodules) according to the American Joint Committee on Cancer (AJCC). - Previously treated with at least one platinum-based chemotherapy. - Before study entry, a minimum of 28 days must have elapsed since any prior chemotherapy. - Prior radiation therapy is allowed as long as the irradiated area is not the only source of measurable disease. - No other forms of cancer therapy, such as radiation, immunotherapy for at least 2 weeks before the enrollment in study. - Performance status of 0-2 on the ECOG criteria. - At least one unidimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1) - Estimated life expectancy of at least 8 weeks. - Patient compliance that allow adequate follow-up. - Adequate hematologic (WBC count 4,000/mm3, platelet count 150,000/mm3), hepatic (bilirubin level 1.5 mg/dL, AST/ALT 80 IU/L), and renal (creatinine concentration 1.5 mg/dL) function. - Informed consent from patient or patient's relative. - Males or females at least 18 years of age. - If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment. - Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs Exclusion Criteria: - Presence of small-cell lung cancer alone or with NSCLC - Unresolved chronic toxic effects from previous anticancer therapy: but patient could be enrolled, if they have recovered from any treatment-related toxicities NCI CTCAE grade ≤2 - Inability to swallow tablets - Second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin or prior malignancy treated more than 5 years ago without recurrence). - More than three previous chemotherapy regimens for NSCLC - Previous treatment with any EGFR-TKI - Patients who have been exposed to any prior HDAC inhibitor, with the exception of exception of valpronic acid used for treating seizures, provided there is a 30-day washout period - Patients with active HIV or hepatitis B or C infection - Concomitant use of phenytoin, carbamazepine, rifampicin, barbiturates, cyclosporine A, valpronic acid, Phenobarbital, ketoconazole, coumarin-derivative anticoagulants or St John's wort; severe or uncontrolled systemic disease; clinically active interstitial lung disease (except uncomplicated lymphangitic carcinomatosis) pregnancy; and breastfeeding. - MI within preceding 6 months or symptomatic heart disease, including unstable angina, congestive heart failure or uncontrolled arrhythmia - Serious concomitant infection including postobstructive pneumonia - Major surgery other than biopsy within the past two weeks. | |
| 23 | NCT01154387 | unknown status | 1 | phase 1/phase 2 | ['end stage renal disease', 'renal transplant'] | ["['N18.6', 'I12.0', 'I13.11', 'I13.2']", "['N25.0', 'Q61.4', 'N23', 'N26.9', 'P96.0', 'Q60.0', 'Q60.1']"] | ['anti-thymocyte globulin', 'tol101', 'tol101', 'steroids', 'tacrolimus', 'mycophenolate mofetil (mmf)'] | ['COC1=CC=CC=C1OCC(O)CO', '[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', 'COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O', 'COC(=O)\\C=C\\C(O)=O'] | Inclusion Criteria: - Recipient of a primary renal transplant from a living or standard criteria cadaveric donor - Male or female 18-60 years of age - Recipient with a PRA < 20% Exclusion Criteria: - Previous solid organ transplant - Recipient of HLA-identical kidney allograft transplant - Recipient of an ABO incompatible donor kidney - Known HIV infection or other major infection - History of malignancy within 3 years (excluding treated basal cell or squamous cell carcinoma of the skin) prior to enrollment - History of tuberculosis - Recipient with cardiovascular disease - Treatment with immunosuppressive medications within 1 month prior to enrollment - Known or suspected allergy to mice - Pregnant or lactating - Unable or unwilling to participate in all required study activities for the duration of the study (6 months) | |
| 24 | NCT01009346 | terminated | toxicity | 0 | phase 1/phase 2 | ['head and neck cancer'] | ["['C76.0', 'C47.0', 'C49.0', 'C77.0', 'D17.0', 'D21.0', 'D36.11']"] | ['rad001', 'cetuximab', 'cisplatin', 'carboplatin'] | ['[H][C@@]1(C[C@@H](C)[C@]2([H])CC(=O)[C@H](C)\\C=C(C)\\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\\C=C\\C=C\\C=C(C)\\[C@H](C[C@]3([H])CC[C@@H](C)[C@@](O)(O3)C(=O)C(=O)N3CCCC[C@@]3([H])C(=O)O2)OC)CC[C@@H](O)[C@@H](C1)OC', '[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\\C1=CSC(N)=N1)C(O)=O', '[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', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck, with recurrent or metastatic disease. 2. Patients 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 11 for the evaluation of measurable disease. 3. Patients must have had no prior monoclonal antibodies or small molecule tyrosine-kinase inhibitors for the treatment of recurrent or metastatic SCCHN. In addition, no prior chemotherapy for the treatment of recurrent or metastatic SCCHN is allowed. 4. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Patients must be greater than or equal to 12 weeks from completion of prior curative intent therapy including surgery, radiation, or systemic anticancer therapy. If palliative radiation therapy is given for recurrent or metastatic disease, patients must be greater than or equal to four weeks from treatment. 5. No concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Patients with prior history of malignancies must be disease free for greater than or equal to two years. 6. Age >18 years. 7. Life expectancy of greater than 4.5 months. 8. ECOG performance status <2 (Karnofsky >60%; see Appendix A). 9. Patients must have normal organ and marrow function as defined below: - leukocytes >3,000/mcL - absolute neutrophil count >1,500/mcL - platelets >100,000/mcL - total bilirubin less than or equal to 1.5 X institutional upper limit of normal or within normal institutional limits. or - AST(SGOT)/ALT(SGPT) <3.0 X institutional upper limit of normal - creatinine within normal institutional limits OR - creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal 3.1.8 10. As the investigational agent RAD001 requires enteral administration, patients must be able to receive adequate enteral nutrition by mouth or through a G-tube device. 11. The effects of RAD001 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 12. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. 2. Patients may not be receiving any other investigational agents. 3. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or other agents used in the study. 5. Patients receiving any medications or substances that are inhibitors or inducers of the isoenzyme CYP3A are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in the appendix. 6. Patients receiving chronic treatment with systemic steroids or other immunosuppressive agents are ineligible. 7. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycin (sirolimus, temsirolimus) or its excipients. 8. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g. ulcerative disease; uncontrolled nausea, vomiting, or diarrhea; malabsorption syndrome or small bowel resection). 9. Patients with active bleeding diathesis or patients on oral anti-vitamin K agent (excluding low dose warfarin). 10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, severely impaired lung function or psychiatric illness/social situations that would limit compliance with study requirements Severely impaired lung function is defined as spirometry and DLCO that is 50% of the normal predicted value and /or O2 saturation that is 88% or less on room air. 11. Pregnant women are excluded from this study because RAD001 is a mTOR 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 RAD001, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. 12. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RAD001. 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. |
| 25 | NCT02890511 | completed | 1 | phase 1/phase 2 | ['solid tumor', 'stage iv gastric cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['paclitaxel'] | ['[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: 1. Patients between 18 and 70 years old 2. Patients prognosed with advanced or metastatic solid cancer by histopathology or cytology analysis who have no available standard therapy or who have failed at least once with the standard therapy 3. Adequate bone marrow function, liver function and adequate kidney function 4. Eastern Cooperative Oncology Group performance status ≤ 2 5. Life expectancy of 3 month or more 6. Written informed consent Exclusion Criteria: 1. Major infectious or neurological disease and bowel obstruction 2. Brain metastasis or hematologic malignancy 3. Patients who underwent surgery, radiation therapy, hormone or chemotherapy within 4 weeks prior to the beginning of investigational drug administration 4. Patients with the history of failure to the taxane line of chemotherapy (with the exception of when it was used before 6 month as adjuvant therapy or when the treatment was discontinued due to docetaxel related side effect) 5. Patients who are required to continuously take P-gp (P-glycoprotein) suppressor, immune suppressor, proton-pump inhibitor or H2-receptor antagonist during clinical trial period 6. Patients deemed by the investigator to suffer from severe heart disease (myocardial infarction, congestive heart failure, arrythmia accompanying drastic changes on ECG, severe or unstable angina pectoris, or other severe heart disease) or accompanying other severe internal diseases (such as uncontrollable diabetes, chronic obstructive pulmonary disease) 7. Patients with prior history of participating in a clinical trial within 30 days from registration for current clinical trial 8. Patient with history of alcohol or drug abuse in the recent 3 months 9. Pregnant women, nursing mothers, or patients of childbearing age who did not agree to contraception (both men and women) 10. Patients with (or suspected to have) abnormality in bile acid secretion (e.g.,. patients with resected gallbladder) 11. Patients who had a history of serious gastrointestinal bleeding, or with diseases that could affect the absorption of oral medication (malabsorption syndrome, active peptic ulcer) 12. Patients with history of severe hypersensitive reaction to active ingredient and excipient of the investigational drug 13. Patient who are in a state that is deemed inappropriate to participate in the clinical trial by the investigator | |
| 26 | NCT00334932 | unknown status | 0 | phase 1/phase 2 | ['multiple myeloma and plasma cell neoplasm'] | ["['C96.20', 'C96.29', 'D47.09']"] | ['bortezomib', 'melphalan', 'pegylated liposomal doxorubicin hydrochloride'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O', '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'] | DISEASE CHARACTERISTICS: - Diagnosis of multiple myeloma - Stage I, II, or III disease according to Durie-Salmon staging criteria - Progressive disease, defined as one of the following: - For secretory disease: - A 25% increase in serum M-protein or Bence Jones protein (an absolute increase of 0.5 g/dL serum M-protein or ≥ 200 mg/24 hours of urine light chain excretion) - For nonsecretory disease: - Bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of ≥ 10% over prior known level - Development of new or worsening existing lytic bone lesions or soft tissue plasmacytomas - Hypercalcemia (i.e., calcium > 11.5 mg/dL) - Relapsed after complete response - Must have received ≥ 2 of the following therapeutic regimens for multiple myeloma: - Nonmyeloablative transplantation - No significant graft-versus-host disease - At least 30 days since prior immunosuppressive therapy (concurrent prednisone allowed provided dose is ≤ 10 mg daily) - Mobilization with chemotherapy followed by either single or tandem autologous stem cell transplantation (considered 1 prior regimen) - Mobilization with chemotherapy followed by autologous and subsequent nonmyeloablative allogeneic stem cell transplantation (considered 1 prior regimen) - Any combination of drugs given concurrently (considered 1 prior regimen) PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Life expectancy ≥ 3 months - Absolute neutrophil count > 1,000/mm^3 (no colony-stimulating factors) - Platelet count > 50,000/mm^3 (no transfusion support) - Bilirubin ≤ 2.0 mg/dL - AST ≤ 4 times upper limit of normal - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment - No history of allergic reaction to compounds containing boron or mannitol - No active uncontrolled viral (including HIV), bacterial, or fungal infection - No motor or sensory neuropathy ≥ grade 2 - No myocardial infarction within the past 6 months - No New York Heart Association class III or IV heart failure - No uncontrolled angina - No severe uncontrolled arrhythmia - No acute ischemia by EKG - LVEF ≥ 35% by MUGA (MUGA required in patients whose lifetime cumulative doxorubicin hydrochloride dose > 400 mg/m^2) PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No grade III or IV toxicity due to previous antineoplastic therapy (except alopecia) - At least 3 weeks since prior chemotherapy - No prior doxorubicin HCl liposome, melphalan, and bortezomib as combination therapy (single or two-drug combinations of these are allowed) - No concurrent corticosteroids (≤ 10 mg prednisone/day or equivalent allowed) - No other concurrent chemotherapy - No concurrent thalidomide - No other concurrent investigational therapy - No other concurrent antineoplastic treatment for multiple myeloma, including clarithromycin - No concurrent radiation therapy - No concurrent nonsteroidal anti-inflammatory agents | |
| 27 | NCT00099463 | completed | 1 | phase 1 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['vaccine', 'vrc-srsdna015-00-vp'] | ['[O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O'] | - INCLUSION CRITERIA: A participant must meet all of the following criteria: 18 to 50 years old. Available for clinical follow-up through Week 32 of the study. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. Complete an Assessment of Understanding prior to enrollment and verbalize understanding of all questions answered incorrectly. Able and willing to complete the informed consent process. Willing to receive HIV test results and wiling to abide by NIH guidelines for partner notification of positive HIV results. Willing to donate blood for sample storage to be used for future research. In good general health without clinically significant medical history and has satisfactorily completed screening. Physical examination and laboratory results without clinically significant findings within the 28 days prior to enrollment. Laboratory Criteria within 28 Days prior to Enrollment: Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men. WBC = 3,300-12,000 cells/mm(3). Absolute neutrophil count (ANC) within institutional normal range. Total lymphocyte count greater than or equal to 800 cells/mm(3). Platelets within institutional normal limits. ALT (SGPT) less than or equal to upper limit of normal. Serum creatinine less than or equal to upper limit of normal. Normal urinalysis defined as negative glucose, negative or trace protein, and no clinically significant blood in the urine. Negative FDA-approved HIV blood test. (Note: Results of HIV ELISA will be documented, but a negative HIV PCR will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study). Negative Hepatitis B surface antigen. Negative anti-HCV (hepatitis C virus antibody) and negative HCV PCR. Female Specific Criteria: Negative beta-HCG pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential. A female participant must meet any of the following criteria: No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation; Or Participant agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 32 of the study; Or Participant agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 32 of the study by one of the following methods: Condoms, male or female, with or without a spermicide; Diaphragm or cervical cap with spermicide; Intrauterine device; Contraceptive pills or patch, Norplant, Depo-Provera or other FDA-approved contraceptive method; Male partner has previously undergone a vasectomy for which there is documentation. EXCLUSION CRITERIA: A volunteer will be excluded if one or more of the following conditions apply: Women: Woman who is breast-feeding or planning to become pregnant during the 32 weeks of study participation. Volunteer has received any of the following substances: Immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis). Blood products within 120 days prior to HIV screening. Immunoglobulin within 60 days prior to HIV screening. Investigational research agents within 30 days prior to initial study vaccine administration. Live attenuated vaccines within 30 days prior to initial study vaccine administration. Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal, or allergy treatment with antigen injections, within 14 days of study vaccine administration. Current anti-TB prophylaxis or therapy. Volunteer has a history of any of the following clinically significant conditions: Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain. Autoimmune disease or immunodeficiency. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids. Diabetes mellitus (type I or II), with the exception of gestational diabetes. History of thyroidectomy or thyroid disease that required medication within the past 12 months. Serious angioedema episodes within the previous 3 years or requiring medication in the previous two years. Hypertension that is not well controlled by medication or is more than 145/95 at enrollment. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws. Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of study. Seizure disorder other than: 1) febrile seizures under the age of two, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) a singular seizure not requiring treatment within the last 3 years. Asplenia, functional asplenia or any condition resulting in the absence or removal o the spleen. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder requiring therapy that has not been well controlled on medication for the past two years; disorder requiring lithium; or suicidal ideation occurring within five years prior to enrollment. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent. Allergic reaction to aminoglycoside antibiotics. | |
| 28 | NCT01082068 | completed | 1 | phase 1/phase 2 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['xl147 (sar245408)', 'xl765 (sar245409)', 'letrozole (femara)'] | ['COC1=CC=C(Cl)C(NC2=C(NS(=O)(=O)C3=CC(NC(=O)C(C)(C)N)=CC=C3)N=C3C=CC=CC3=N2)=C1', 'CCN1C(=O)C(=CC2=C(C)N=C(N)N=C12)C1=CC=NN1', 'N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N'] | Inclusion Criteria: - The subject has histologically confirmed breast cancer that is ER+ and/or PGR+. - The subject's breast cancer is negative for HER2. - The subject has recurrent or metastatic breast cancer that is refractory to a nonsteroidal aromatase inhibitor and has either disease progression or disease recurrence. - Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole. - For subjects enrolled in Phase 2, either archival tumor samples must be available, or the subject must be willing to undergo a fresh biopsy. - In Phase 2, at least 30 subjects in each arm must have measurable disease - The subject is a postmenopausal female. - If a subject is currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least 2 months before starting study treatment. - The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. - The subject has adequate organ and marrow function. - The subject has no other diagnosis of malignancy or evidence of other malignancy for 2 years before screening for this study (except non-melanoma skin cancer or in situ carcinoma of the cervix). - The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document. Exclusion Criteria: - The subject has received prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR. - Certain restrictions on prior therapies apply. - The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to pre-therapy baseline. - The subject has untreated, symptomatic, or progressive brain metastases. - The subject has only non-measurable lesions, other than bone, skin, or chest wall metastasis - The subject has to start cytotoxic chemotherapy due to rapid progressive disease involving major organs. - The subject has prothrombin time/ International Normalized Ratio (PT/ INR) or partial thromboplastin time (PTT) test results at screening that are above 1.3 x the laboratory upper limit of normal. - The subject has uncontrolled significant intercurrent illness. - The subject has a baseline corrected QT interval (QTc) > 470 ms. - The subject has a diagnosis of uncontrolled diabetes mellitus. - The subject is known to be positive for the human immunodeficiency virus (HIV). - The subject has a previously identified allergy or hypersensitivity to components of the study treatment formulation(s). - The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee. | |
| 29 | NCT00450138 | completed | 1 | phase 1 | ['head and neck cancer'] | ["['C76.0', 'C47.0', 'C49.0', 'C77.0', 'D17.0', 'D21.0', 'D36.11']"] | ['zd6474 (vandetanib)', 'cisplatin'] | ['COC1=C(OCC2CCN(C)CC2)C=C2N=CN=C(NC3=C(F)C=C(Br)C=C3)C2=C1', '[H][C@@]12N(C)C3=CC(OC)=C(C=C3[C@@]11CCN3CC=C[C@](CC)([C@@]13[H])[C@@]([H])(OC(C)=O)[C@]2(O)C(=O)OC)[C@]1(C[C@@]2([H])CN(CC(CC)=C2)CC2=C1NC1=CC=CC=C21)C(=O)OC'] | Inclusion Criteria: - Stage III-IV squamous cell carcinoma of the head and neck Exclusion Criteria: - No previous treatment for head and neck cancer, adequate cardiac function | |
| 30 | NCT01340066 | completed | 1 | phase 1/phase 2 | ['urinary incontinence'] | ["['N39.492', 'R32', 'R39.81', 'N39.498', 'L24.A2']"] | ['uish001', 'matching placebo'] | ['CC1=CC(O)=CC(C)=C1Cl'] | Inclusion Criteria: - Women who have moderate to severe urge, stress or mixed Urinary Incontinence Exclusion Criteria: - Medical history of migraines, neurologic problems, swallowing disorder, stroke or severe depression. - Medical history of heart failure, peripheral edema or moderate to severe asthma or chronic obstructive pulmonary disease (COPD) - Certain restricted medications - Any other condition that would interfere with the safety of the subject | |
| 31 | NCT00306202 | completed | 1 | phase 1 | ['leukemia'] | ["['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']"] | ['dasatinib', 'dasatinib', 'dasatinib'] | ['CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1'] | For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: - Ph-positive (Ph+) Chronic Myelogenous Leukemia in chronic, accelerated or blast phase or Ph+ acute lymphoblastic leukemia (ALL) with imatinib-resistant disease or intolerance to imatinib. - Ph-negative acute leukemia in second or subsequent relapse - Age >1 and <21 years - Lansky or Karnofsky scale >60 - Life expectancy >3 weeks - Adequate hepatic and renal function - Written informed consent Exclusion Criteria: - Subjects for whom potentially-curative therapy was available, including electing immediate [ie, planned <45 days] stem-cell transplantation. Subjects in Stratum 1 were to have had an ongoing identical HLA donor search, and may have discontinued study if a donor became available.) - Subjects with symptomatic central nervous system (CNS) disease (eg, convulsions due to their CNS disease). - Subjects who had not recovered from acute toxicity of previous therapy. - Clinically-significant disorder of platelet function (eg, von Willebrand's disease) or ongoing gastrointestinal bleeding. - Serious uncontrolled medical disorder or active infection - Uncontrolled or significant cardiovascular disease - Use of any investigational agent or any other anticancer agent within 14 days prior to treatment start. - Prior therapy with dasatinib - Subjects taking medications that irreversibly inhibit platelet function or anticoagulants. - Subjects taking certain medications that are accepted to have a risk of causing QTc prolongation. - Women of Child Bearing Potential with a positive pregnancy test prior to study drug administration. - Expected noncompliance, or unable to have regular follow-up due to psychologic, social, familial, or geographic reasons. - Subjects who are compulsorily detained for legal reasons or treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this study. | |
| 32 | NCT00904423 | terminated | low accrual | 0 | phase 1/phase 2 | ['breast cancer', 'bone diseases'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['M83.4', 'H05.321', 'H05.322', 'H05.323', 'H05.329']"] | ['vitamin d'] | ['CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])\\C(CCC[C@]12C)=C\\C=C1\\C[C@@H](O)CCC1=C'] | Inclusion Criteria: 3.1.1 All postmenopausal women with histology-confirmed invasive primary breast cancer, who have completed primary surgical or radiotherapy (XRT) with or without adjuvant chemotherapy and are candidates to receive adjuvant therapy with aromatase inhibitors will be screened for eligibility. Postmenopausal is defined as satisfying one or more of the following criteria: having had bilateral oophorectomy; aged more than 60 years; or aged 55-59 years with an intact uterus and amenorrheic for at least 12 months; or if amenorrheic for less than 12 months (after receiving hysterectomy, hormone therapy or chemotherapy). 3.1.2 At the time of study enrollment, participants will have completed primary surgical or XRT with or without adjuvant chemotherapy. Chemotherapy will be completed at least 28 days prior to enrollment. 3.1.4 Participants will be women between 18-85 years of age. Women and minorities will be actively recruited. Though breast cancer extremely rarely occurs in children and men, this study will only recruit adult females. 3.1.5 Participants will have a life expectancy of at least 5 years. 3.1.6 Participants will have Eastern Clinical Oncology Group (ECOG) performance status 0-2. 3.1.7 Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: 3.2.1 Medications affecting bone metabolism (bisphosphonates, anticonvulsants, chronic heparin therapy, chronic glucocorticoid use > 5 mg/day prednisone or equivalent, teriparatide). 3.2.2 Use of any investigational drug within past 90 days. 3.2.3 Metastatic breast cancer. High risk for osteoporosis/fractures (BMD < -2.0, history of non-traumatic fracture). Hyperparathyroidism Hypercalcemia Hypercalciuria (fasting spot urine calcium/creatinine ratio >0.20) History of renal stones Renal failure with creatinine over 2.0 3.2.4 Considering that vitamin D3 is produced by the human body, allergy to vitamin D3 is not expected to develop. Subjects with known history of allergic reaction to compounds used to manufacture capsules (rice powder) will be excluded form this study. 3.2.5 Recent history of excessive alcohol or drug use. 3.2.6 As this study will recruit post-menopausal patients, thus pregnant or nursing patients are not part of this investigation. 3.2.8 This study is designed to study women after completing primary therapy for breast cancer. Survivors of previous cancers and HIV-positive subjects will not be excluded. |
| 33 | NCT00716456 | completed | 0 | phase 1/phase 2 | ['lung adenocarcinoma'] | ["['D02.20', 'D02.21', 'D02.22']"] | ['erlotinib with cetuximab'] | ['COCCOC1=CC2=C(C=C1OCCOC)C(NC1=CC(=CC=C1)C#C)=NC=N2'] | Inclusion Criteria: - Pathologic evidence of lung adenocarcinoma confirmed at MSKCC - Measurable (RECIST) indicator lesions not previously irradiated - Radiographic progression by RECIST during treatment with erlotinib - Received treatment with erlotinib throughout the one month prior to enrollment - Received treatment with erlotinib for >3 months - At least one of the following: - Previously received treatment with erlotinib, gefitinib, or an investigational EGFR TK inhibitor (patients may have received other treatments subsequently including radiation or chemotherapy) and had a radiographic partial or complete response to treatment as defined by RECIST criteria - A documented mutation in EGFR exons 19 or 21. - Karnofsky performance status ≥ or = to 70% - Total bilirubin: within normal institutional limits. AST/(SGOT)/ALT(SGPT)< or = to 2.5 X institutional upper limit of normal (ULN) - Signed informed consent - Effective contraception * - Age > 18 years old *Sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. All WOCBP MUST have a negative pregnancy test within two weeks prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study. Exclusion Criteria: - CNS lesions which are symptomatic and/or requiring escalating doses of corticosteroids. - 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. - Prior cetuximab or panitumumab. Prior severe infusion reaction to a monoclonal antibody. - Current grade 2 or greater skin toxicity on erlotinib therapy - Radiotherapy ≤ or = to 14 days prior to enrollment - Any investigational agent or therapy ≤ or = to 30 days before enrollment - Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (except erlotinib) ≤ or = to 30 days before enrollment - Women who are pregnant or lactating. - Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection - Major surgery within 28 days or minor surgery within 14 days of study enrollment - Men or women of child-bearing potential (women who are post-menopausal < 52 weeks, not surgically sterilized, or not abstinent) not consenting to use adequate contraception (per institutional standard of care) during the course of the study and after the last investigational product(s) administration (24 weeks for women, 4 weeks for men) | |
| 34 | NCT00402415 | terminated | 0 | phase 1 | ['tumors'] | ["['E88.3', 'R97.8', 'C49.A0', 'C49.A1', 'C49.A2', 'C49.A5', 'C49.A3']"] | ['sunitinib malate', 'rapamycin'] | ['CCN(CC)CCNC(=O)C1=C(C)NC(\\C=C2/C(=O)NC3=C2C=C(F)C=C3)=C1C', '[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](O)[C@@H](C1)OC'] | Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective. Patients with previously untreated metastatic renal cell carcinoma are eligible. - Patients must have measurable disease by RECIST criteria. - Patients must have at least 1 lesion located in the neck, lung, solid organ (including liver) or soft tissue in abdomen or pelvis, or soft tissue in lower extremities that is 3 cm and ideally <7 cm in the transaxial plane. Larger lesions may be considered if they meet all other criteria. Index lesions must be well demarcated. - ECOG performance status of 0-1. - Must be ≥18 years of age. - Expected survival of at least 3 months. - Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device), and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Nursing patients are excluded. Sexually active men must also use acceptable contraceptive methods. Pregnant and nursing patients are excluded because the effects of the combination of SU11248 (Sutent®) and sirolimus on a fetus or nursing child are unknown. - Must be able and willing to give written informed consent. - Patients must have the following clinical laboratory values: ANC count ≥1500/mm3; Platelets ≥100,000/mm3; Serum creatinine ≤2x upper limit of normal. If serum creatinine is above the upper limit of normal (but less than 2x normal), patients must have a measured 24 hour urine creatinine clearance ≥ 50 ml/min to be eligible; Total bilirubin < 1.5x upper limit of normal; Serum calcium < 12.0 mg/dl; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3x the upper limit of normal; Prothrombin Time (PT), activated partial thromboplastin time (aPTT) and INR in the normal range;. Hemoglobin ≥9 gm/dl (may be corrected by transfusion). - Normal cardiac ejection fraction Exclusion Criteria: - Diagnosis or history of central nervous system (CNS) disease (i.e. primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis). - Any active uncontrolled bleeding and any patient with a bleeding diathesis (for example, active peptic ulcer disease). Any grade 3 hemorrhage within 4 weeks prior to starting treatment. - Any ongoing coagulopathies or receiving anticoagulants. - Hypertension that cannot be controlled by medications (>150/100 mm Hg despite optimal medical therapy). - QTc interval > 500 msec on baseline EKG. - Cardiac ejection fraction below institutional lower limit of normal. - Measured 24-hour urine creatinine clearance < 50 ml/min. - Active infection of any kind. - Unwilling or unable to follow protocol requirements or to give informed consent. - Dyspnea at rest or with minimal exertion. - No treatment with cytotoxic or biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 4 weeks must have elapsed from any prior surgery, radiation, hormonal or other drug therapy for their cancer. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible. - Any of the following within 6 months prior to first dose of treatment: myocardial infarction, symptomatic coronary artery disease (severe or unstable angina), artery bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolus. - Known HIV infection. Patients with HIV infection are excluded because there may be unknown or dangerous drug interactions between sirolimus/SU11248 (Sutent®) and the anti-retroviral agents used to treat HIV infections. - Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication. - Diagnosis of second malignancy (except malignancies treated with no evidence of recurrence for at least 5 years, and curatively treated basal cell or squamous cell carcinomas of the skin, or in situ cervical cancer, or any stage I malignancy > 2 years from treatment). - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study. - Patients taking concurrent medications of any kind which are strong inducers or inhibitors of CYP3A4. Patients receiving any of the following will be excluded: ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, St. John's Wort. | |
| 35 | NCT00598091 | terminated | low accrual, unable to meet endpoint in timely manner | 0 | phase 1 | ['refractory solid tumors', 'pancreatic adenocarcinoma'] | ["['D46.4', 'D46.1', 'D46.A', 'D46.0', 'D46.20', 'D46.21', 'D46.22']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['gemcitabine', 'dasatinib', 'gemcitabine', 'dasatinib'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1'] | Inclusion Criteria: Eligibility Criteria Specific for Dose Escalation Phase - Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard therapy would include gemcitabine or for which standard curative or palliative measures do not exist or are no longer effective. - Patients must not have had radiation therapy, hormonal therapy, biologic therapy or chemotherapy for cancer within the 28 days prior to study day 1. Eligibly Criteria Specific for Expansion Phase at Recommended Phase II Dose - Histologically or cytologically documented adenocarcinoma of the pancreas. - Metastatic pancreatic cancer as documented by radiologic study or surgical evidence of metastatic disease. - No prior chemotherapy for metastatic pancreatic disease. Patients may have received a radiosensiting dose of 5-fluorouracil or capecitabine or other agents used as radiosensitizers with concurrent radiation therapy. - Last dose of adjuvant chemotherapy must be at least 4 weeks prior to day 1 of the study drug treatment - Prior radiation therapy is allowed. prior to day 1 of the study drug treatment. At least 4 weeks must have elapsed to baseline or grade 1. - No prior treatment with gemcitabine or dasatinib in the adjuvant or metastatic setting. - Prior gemcitabine only allowed if the gemcitabine was administered in the adjuvant setting and > 6 months has elapsed between diagnosis of metastatic disease and last gemcitabine treatment. - No history for other carcinomas within the last five years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with a current PSA of <1.0 mg/dL on 2 successive evaluations, at least 3 months apart, with the most recent evaluation no more than 4 weeks prior to day 1 of the study drug treatment. . Eligibility Criteria for All Subjects - Age >18 years. - Karnofsky performance status >70%. - Life expectancy of at least 3 months. - Ability to understand and the willingness to sign a written informed consent document. - Must meet lab requirements as defined in the protocol - Patients should be capable of taking oral medications for prolonged compliance. - Sexually active women of childbearing potential must use an effective method of birth control. - All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. - Pregnant and/or lactating women will be excluded from this study. Exclusion Criteria: - Patients who have had radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for cancer within 28 days prior to day 1 of the study drug treatment. Patients receiving hormonal therapy for metastatic prostate or breast cancer may continue hormonal therapy. - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 1 of the study drug treatment - Core biopsy or other minor surgical procedure excluding study-related procedures or placement of a vascular access device within 7 days prior to expected start of treatment. - Patients who have received any other investigational agents within the 28 days prior to day 1 of the study drug treatment. - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption - History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to day 1 of the study drug treatment. - History of stroke or transient ischemic attack within 6 months prior to day of the study drug treatment. - Uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class II or greater - Known cardiomyopathy with decreased ejection fraction (less than institutional normal limits) - Diagnosed or congenital long QT syndrome - Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes) - Prolonged QTc interval on pre-study electrocardiogram (> 450 msec) - Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the previous 6 months of day 1 of the study drug treatment - Evidence of bleeding diathesis or coagulopathy. Patients on therapeutic anticoagulation may be enrolled provided that they have been clinically stable on anti-coagulation for at least 2 weeks prior to day 1 of the study drug treatment - History of significant bleeding disorder unrelated to cancer - Medications that inhibit platelet function - Fluid retention (i.e. pleural effusion, ascites, edema) grade > 2. - A known history of HIV seropositivity, hepatitis C virus, acute or chronic active hepatitis B infection, or other serious chronic infection requiring ongoing treatment. - Patients currently taking drugs that are generally accepted to have a risk of causing Torsades de Pointes - Patients actively taking inhibitors or inducers of CYP3A4 - Patients actively taking proton pump inhibitors or H2 antagonists - Other concurrent severe and/or poorly controlled medical condition that could compromise safety of treatment - Any psychiatric illness/social situations that would limit safety or compliance with study requirements or may interfere with the interpretation of the results. - Patients unwilling to or unable to comply with the protocol. |
| 36 | NCT00513214 | completed | 1 | phase 1/phase 2 | ['type 2 diabetes'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['xoma 052', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - American Diabetes Association (ADA) diagnostic criteria for T2D - Fasting blood glucose concentration ≥ 126 mg/dL (≥ 7.0 mmol/L) (must be measured within 35 days prior to Day 0) OR Symptoms of hyperglycemia (e.g., thirst, polyuria, weight loss, visual blurring) AND a casual/random plasma glucose value of ≥ 200 mg/dL (≥ 11.1 mmol/L) (must be measured within 35 days prior to Day 0) - HbA1c ≥ 7.5% and ≤ 12% (DCCT standard) - Current T2D of duration > 6 months at Screening - T2D and other diseases must be stable. Stable disease is defined as disease that is judged stable by the investigator and which did not require a change in medications or dosing level on 4 or more consecutive days or 7 days in total within 35 days prior to Day 0. - Age ≥ 18 and ≤ 70 at Screening - Weight ≥ 80 lbs (36.3 kg) and ≤ 325 lbs (147.4 kg) - BMI ≥ 23 and ≤ 40 kg/m2 - For female subjects of child-bearing age, a negative serum pregnancy test. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study. - Agree not to change diet and exercise regimen during the trial Exclusion Criteria: - Use of the following medications - Anti-inflammatory therapy other than aspirin ≤ 100 mg/day; Immunosuppressive treatment; Beta 2 and non-selective adrenergic blockers (Note: selective beta 1 blockers are permitted); Thiazolidinediones; Glucagon-like peptide (GLP) agonists including DPP4 inhibitors - Change in medication for diabetes within 35 days prior to Day 0, defined as a change in dosing level on 4 or more consecutive days or 7 days in total - Fasting C-peptide < 400 pM (< 1.20 μg/L) - Hemoglobin < 8.0 g/dL, WBC < 3.0 X 103/mm3, platelet count < 125 X 103/mm3, creatinine > 1.5 mg/dL, AST/ALT > 2 X ULN, alkaline phosphatase > 2 X ULN - Positive for GAD65 or IA-2 auto-antibodies - Known HIV antibody, hepatitis B surface antigen, and/or hepatitis C antibody - History of malignancy within 5 years prior to study entry other than carcinoma in situ of the cervix, or adequately treated, non-metastatic squamous or basal cell carcinoma of the skin - History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies - History of tuberculosis, positive PPD test, active atopic disease requiring medication, or asthma - Infectious disease - CRP > 30 mg/L, fever, or infection requiring treatment with antibiotics within 3 weeks prior to Screening; History of recurrent infection or predisposition to infection; Active leg or foot ulcer - Immunodeficiency - Female subjects who are pregnant, planning to become pregnant during the course of the study, or breast-feeding - History or symptoms of a demyelinating disease - Clinically significant diabetic macular edema and/or proliferative diabetic retinopathy by history or fundoscopy - Receipt of a live (attenuated) vaccine within 3 months prior to Screening - Major surgery within 35 days prior to Day 0 - Participation in an investigational drug or device trial within 30 days prior to Screening - Use of a therapeutic monoclonal antibody within 90 days prior to Screening - Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to the study drug | |
| 37 | NCT00121290 | completed | 1 | phase 1 | ['unspecified adult solid tumor, protocol specific'] | ["['H01.009', 'H02.209', 'H02.009', 'H02.109', 'H04.209', 'H05.409', 'H10.509']"] | ['sjg-136'] | ['COC1=CC2=C(C=C1OCCCOC1=CC3=C(C=C1OC)C(=O)N1CC(=C)C[C@H]1C=N3)N=C[C@@H]1CC(=C)CN1C2=O'] | Inclusion Criteria: - Patients must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective - Prior chemotherapy or immunotherapy allowed - Time interval must be at least 4 weeks since prior chemotherapy or immunotherapy, 6 weeks if the last regimen included BCNU or mitomycin C - Radiation therapy to < 25% of hematopoietic bone marrow is allowed - ECOG performance status =<2 (Karnofsky >= 60%) - Life expectancy of greater than three months - Recovered from prior therapy - Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation - Ability to understand and the willingness to sign a written informed consent document - WBC >= 3,000/mm^3 - Absolute neutrophil count >= 1,500/mm^3 - Platelet count >= 100,000/mm^3 - Bilirubin normal - AST and ALT =< 2.5 times upper limit of normal - Creatinine =< 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min - No unstable angina pectoris Exclusion Criteria: - Patients receiving any other investigational agents - 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 - Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SJG-136, breastfeeding should be discontinued if the mother is treated with SJG-136 - History of allergic reactions attributed to compounds of similar chemical or biologic composition to SJG-136 - HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with SJG-136 - With the exception of alopecia (and other situations in which the organ dysfunction or symptoms are considered clinically insignificant or irrelevant to this study), patients may not have baseline organ dysfunction or symptoms that qualify as Grade 2 or greater by CTC AE v. 3.0 - No other chemotherapy, immunotherapy, radiation therapy, surgery for cancer (including resection of any metastases), specific antitumor therapy, or experimental medications will be permitted while the patients are participating in this study - Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier - Palliative radiation therapy is not allowed | |
| 38 | NCT00512668 | terminated | 0 | phase 1 | ['adenocarcinoma of the prostate', 'recurrent prostate cancer'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['leuprolide acetate', 'goserelin acetate', 'bicalutamide', 'nilutamide', 'flutamide', 'temsirolimus'] | ['CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O', 'CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O', '[H][C@]12SCC(C)=C(N1C(=O)[C@H]2NC(=O)[C@H](N)C1=CC=C(O)C=C1)C(O)=O', 'CC1(C)NC(=O)N(C1=O)C1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F', 'CC(C)C(=O)NC1=CC(=C(C=C1)[N+]([O-])=O)C(F)(F)F', 'CN1N=NC2=C(N=CN2C1=O)C(N)=O'] | Inclusion Criteria: - All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must also have signed an authorization for the release of their protected health information - Patients must have histologically confirmed adenocarcinoma of the prostate recurring after local therapy (radical prostatectomy and/or radiation therapy) as evidenced by rising serum PSA - Prostate-Specific Antigen (PSA) Doubling Time (PSADT) =< 12 months after local therapy (prostatectomy and/or definitive radiation) as determined by linear regression of all available PSA values within 6 months of initiation of androgen ablation (for patients who underwent prostatectomy, at least one PSA measurement of >= 1.0 ng/mL; for patients who underwent radiation, at least one PSA measurement of >= 3.0 ng/mL and >= 150% postradiation nadir) - No evidence of metastasis as determined by bone scan or computed tomography (CT) scan - Initiation of Androgen Ablation of less than 8 weeks' duration prior to study entry is permitted - Leukocytes ≥ 3,000/mcl - Absolute neutrophil count ≥ 1,000/mcl - Hemoglobin ≥ 8.0g/dl - Eligibility level for hemoglobin may be reached by transfusion - Platelet count >= 100,000/μL - Total bilirubin ≤1.5 X laboratory ULN - AST and/or ALT ≤ 3 X laboratory ULN - Creatinine ≤ 1.5 X laboratory ULN OR calculated creatinine clearance ≥ 60 ml/min/1.73 m^2 for patients w/creatinine levels above the laboratory ULN - Serum cholesterol level < 350 mg/dl - Triglyceride level < 300mg/dl - ECOG performance status 0, 1 or 2 - The effects of Temsirolimus on the developing human fetus are unknown; for this reason men must agree to use contraception from the time of study enrollment continuing for the duration of study participation - Patients must be registered in the MDACC institutional database prior to treatment with study drug - PSA < 40 ng/ml Exclusion Criteria: - Patients with histologic variants other than adenocarcinoma in the primary tumor - Patients may not be receiving any other investigational agents - Patients may not be receiving concomitant immunotherapy or immunosuppressive therapy - Patients may not have received prior systemic treatment for prostate cancer (other than no more than 3 months of prior treatment with androgen ablation in neoadjuvant and/or adjuvant setting and at least a year must have elapsed since last administration) unless initiation of Androgen Ablation of less than 8 weeks' duration prior to study entry is permitted - Patient with uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring parenteral therapy on day 1 of protocol treatment, symptomatic congestive heart failure resulting in a resting O2 saturation of < 92% on room air, unstable angina pectoris, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, known pulmonary hypertension or pneumonitis - Patients in a severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV) due to possible pharmacokinetic interactions with HAART therapy - Patients diagnosed with acute or chronic hepatitis B or C - Patients using immunosuppressive agents, including intravenous corticosteroids, within 3 weeks of study entry - Patients must not have a history of any other cancer (except nonmelanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years | |
| 39 | NCT01133912 | completed | 1 | phase 1 | ['breast cancer'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']"] | ['paclitaxel, gemcitabine, lapatinib'] | ['NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F'] | Inclusion Criteria: - Histologically confirmed and newly diagnosed operable breast cancer - Documented HER2 positive disease : 3+ overexpression by IHC or HER2 gene amplification by FISH - ECOG performance status 0-2 - Age ≥ 18 years - Clinical stage II or III operable breast cancer - Axillary node positivity determined by cytology - No prior hormonal, chemotherapy, or radiotherapy is allowed - No breast operation other than biopsy to make diagnosis is allowed - Negative urine pregnancy test within 7 days prior to registration in premenopausal patients - Adequate hematopoietic function: Absolute granulocyte count ≥1,500/mm3, platelet ≥100,000/mm3, hemoglobin ≥10g/mm3 - Adequate hepatic function: total bilirubin ≤1.5mg/dL, AST/ALT ≤2 x UNL, alkaline phosphatase ≤2 x UNL - Adequate renal function: Serum creatinine ≤1.5mg/dL - Adequate cardiac function: 1. Normal or nonspecific EKG taken within 1 month of enrollment 2. LVEF ≥50% by MUGA or echocardiogram taken within 4 weeks of enrollment - Ability to understand and comply with protocol during study period - Patients should sign a written informed consent before study entry Exclusion Criteria: - Pregnant or lactating women - Patients who received hormonal, chemotherapy or radiotherapy for breast cancer - Patients with bilateral breast cancer - Patients who underwent surgery for breast cancer - Patients with node-negative stage IIA (T2N0) breast cancer - Patients who have history of cancer other than in situ uterine cervix cancer or nonmelanotic skin cancer - Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis) | |
| 40 | NCT01555268 | completed | 1 | phase 1 | ['adult acute megakaryoblastic leukemia (m7)', 'adult acute minimally differentiated myeloid leukemia (m0)', 'adult acute monoblastic leukemia (m5a)', 'adult acute monocytic leukemia (m5b)', 'adult acute myeloblastic leukemia with maturation (m2)', 'adult acute myeloblastic leukemia without maturation (m1)', 'adult acute myeloid leukemia with 11q23 (mll) abnormalities', 'adult acute myeloid leukemia with del(5q)', 'adult acute myeloid leukemia with inv(16)(p13;q22)', 'adult acute myeloid leukemia with t(16;16)(p13;q22)', 'adult acute myeloid leukemia with t(8;21)(q22;q22)', 'adult acute myelomonocytic leukemia (m4)', 'adult erythroleukemia (m6a)', 'adult pure erythroid leukemia (m6b)', 'recurrent adult acute myeloid leukemia', 'untreated adult acute myeloid leukemia'] | ["['C94.21', 'C94.22', 'C94.20']", "['C7A.1']", "['C93.01', 'C93.02', 'C93.00']", "['C93.Z1', 'C93.Z2', 'C93.91', 'C93.92', 'C93.01', 'C93.02', 'C93.Z0']", "['C92.01', 'C92.02', 'C92.00']", "['C92.01', 'C92.02', 'C92.00']", "['R19.5', 'H35.09', 'M26.50', 'M26.59', 'Q99.8', 'R06.89', 'R06.9']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C95.91', 'C95.92', 'Z80.6', 'Z85.6', 'C90.11', 'C90.12', 'C91.01']", "['C92.51', 'C92.52', 'C93.11', 'C93.12', 'C93.31', 'C93.32', 'C92.50']", "['C94.01', 'C94.02', 'C94.00']", "['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']"] | ['cytarabine'] | ['ClCCN(CCCl)P1(=O)NCCCO1'] | Inclusion Criteria: - Diagnosis of AML as defined by the World Health Organization (excluding acute promyelocytic leukemia and chronic myeloid leukemia- blast/accelerated phase) in an adult patient - Patients with newly diagnosed untreated AML for whom the treatment of choice is low-intensity therapy by investigator assessment or who has declined intensive induction therapy recommended by the investigator OR - Patients with refractory or relapsed AML following at least one prior treatment course who are not currently considered eligible for stem cell transplantation at the time of screening due to non-optimal AML disease control, lack of suitable transplantation donor, failure to meet other transplantation criteria, or refusal to undergo transplantation - Eastern Cooperative Oncology Group (ECOG) status 0-2 (ECOG 3 is excluded) - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN) - Creatinine clearance > 40ml/min per 24 hour urine collection or calculated according to the Cockcroft-Gault formula - Urinary protein quantitative value of less than 30mg/dL in urine analysis or less than 1+ on dipstick, unless quantitative protein is < 1000mg in a 24 hour urine sample - Partial thromboplastin time (PTT) or activated (aPTT) =< 1.5 x ULN per institution laboratory range and international normalized ratio (INR) =< 1.5 - Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure - Individuals of childbearing potential must agree to use acceptable contraceptive methods (e.g., double barrier) during treatment Exclusion Criteria: - History of central nervous system involvement with leukemia - History of venous or arterial thromboembolism within 12 months prior to enrollment - History of clinically significant bleeding within 6 months of enrollment - Unresolved toxicities from prior systemic therapies that are Common Terminology Criteria for Adverse Events (CTCAE) version 4 >= Grade 2 in severity except alopecia excluding hematological toxicities attributable to underlying disease - Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor - Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine or tacrolimus - Has not yet completed a 14 day washout period for any previous anti-cancer systemic therapies (30 days for prior bevacizumab) with the exception of hydroxyurea or leukapheresis for uncontrolled leukocytosis - Enrolled in or has not yet completed at least 14 days since ending other investigational device or drug trials, or currently receiving other investigational treatments - Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication or placement of percutaneous transluminal coronary angioplasty/stent - Major surgery within 28 days prior to enrollment or still recovering from prior surgery - Minor surgical procedures, placement of tunneled central venous access device within 3 days prior to enrollment - Uncontrolled hypertension as defined as diastolic > 90mmHg OR systolic > 140mmHg; the use of anti-hypertensive medication to control hypertension is permitted - Non-healing wound, ulcer (including gastrointestinal) or fracture - Active uncontrolled infection, including human immunodeficiency virus (HIV) and active hepatitis infection - Subject not consenting to the use of highly effective contraceptive, e.g., double barrier method (i.e., condom plus diaphragm) precautions during the course of the study and for 6 months after administration of the last study medication - Subject has known sensitivity to any of the products to be administered during dosing - History of allergic reactions to bacterially produced proteins - Subject has previously been enrolled onto this study - Subject will not be available for follow-up assessment - Pregnant or nursing female patients - Active second malignancy other than AML which is not in remission and/or for which the patient is currently receiving treatment - Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures - Any condition which in the investigator's opinion makes the patient an unsuitable candidate for study participation | |
| 41 | NCT01867866 | completed | 1 | phase 1 | ['advanced solid tumors'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']"] | ['tas-102', 'trifluridine'] | ['ClC1=C(CN2CCCC2=N)NC(=O)NC1=O', 'OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(C(=O)NC1=O)C(F)(F)F'] | Inclusion Criteria: 1. Has provided written informed consent 2. Has advanced solid tumors (excluding breast cancer) for which no standard therapy exists 3. ECOG performance status of 0 or 1 4. Is able to take medications orally 5. Has adequate organ function (bone marrow, kidney and liver) 6. Women of childbearing potential must have a negative pregnancy test and must agree to adequate birth control if conception is possible. Males must agree to adequate birth control. Exclusion Criteria: 1. Has had certain other recent treatment e.g. anticancer therapy, received investigational agent, within the specified time frames prior to study drug administration 2. Certain serious illnesses or medical condition(s) 3. Has had either partial or total gastrectomy 4. Has unresolved toxicity of greater than or equal to CTCAE Grade 2 attributed to any prior therapies 5. Known sensitivity to TAS-102 or its components 6. Is a pregnant or lactating female 7. Refuses to use an adequate means of contraception (including male patients) | |
| 42 | NCT00279240 | completed | 1 | phase 1 | ['diabetes'] | ["['E23.2', 'N25.1', 'P70.2', 'O24.92', 'Z83.3', 'Z86.32', 'E10.65']"] | ['metformin'] | ['CSCC[C@H](N)C(O)=O'] | Inclusion Criteria: - Both male and female. 35 - 55 years. No Known history of diabetes. Willing and available for a three years study. Exclusion Criteria: - Pregnant women. Subjects with major illness such as cancer, hepatic or cardiac diseases. Tranferable jobs. | |
| 43 | NCT00500747 | completed | 1 | phase 1 | ['hepatitis c'] | ["['B18.2', 'B17.10', 'B17.11', 'B19.20', 'B19.21', 'B15.0', 'B15.9']"] | ['placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Healthy, hepatitis C virus (HCV) negative. - 18-45 year old healthy adults. Insufficient data are available in adults to judge risk in children. - In good general health as determined by medical history, physical examination and the following screening labs: - Complete Blood Count (CBC): Total WBC (White Blood Cell): 3.5-14 thousand/microliter (MCL); Hemoglobin (Hgb): Men: 12.2-18 g/dl and Women: 10.5-17 g/dl. - Creatinine: Men: less than or equal to 1.4 mg/dl; Women: less than or equal to 1.2 mg/dl. - Glucose: 50 mg/dl to less than or equal to 109 mg/dl. - Alanine Aminotransferase (ALT): Men 2-60 units/litre (U/I): Women: 3-40 U/I. - Aspartate Aminotransferase (AST): Men: 2-50 U/I, Women 2-35 U/I. - Total bilirubin: Men: less than or equal to 1.5 mg/dl: Women: less than or equal to 1.3 mg/dl. - Urinalysis: negative or trace protein, negative glucose, less than or equal to 3 Red Blood Cells (RBC)/High Power Field (HPF) and less than or equal to 5WBC/HPF (in nonmenstruating females). - Negative serum cryoglobulin - Hepatitis B: negative Hepatitis B Surface Antigen (HBsAg) (using standard Food and Drug Administration FDA approved tests, e.g. Abbott or Organon). - Hepatitis C: Anti-Hepatitis C Virus (HCV) negative and HCV Ribonucleic Acid (RNA) negative (using standard FDA approved tests, e.g. Abbott or Organon). - HIV ELISA negative (using standard FDA approved tests, e.g. Abbott or Organon) (Written informed consent for HIV antibody testing will be obtained before obtaining the HIV sample.) Note: HIV vaccine volunteers who test positive by HIV ELISA and HIV western blot testing due to receipt of HIV vaccine may participate if they test negative by HIV DNA Polymerase Chain Reaction (PCR). - Negative urine pregnancy test (females of child bearing potential) obtained at screening and at the day of each immunization. - The ability to understand and sign a written informed consent document. Available for 16 months after the first injection so that follow-up may be completed. Exclusion Criteria: - Diabetes. - Cancer other than squamous cell skin cancer which has been excised. - History of myocardial infarction or arrhythmia requiring hospitalization. - Syncope requiring hospitalization. - Unconsciousness other than a simple concussion. - Seizures other than febrile seizures as a child <5 years of age. - Current liver disease (not including Gilbert's disease). - Autoimmune disease (does not include thyroid disease or vitiligo). - Splenectomy. - Uncontrolled hypertension [blood pressure (BP) >150/90; anti-hypertensive medications are acceptable). - Subjects with identifiable high-risk behavior for HCV infection as characterized by the following: injection drug use (IVDU) or cocaine snorting within the last year. - Subject had a tattoo or body piercing within the past 6 months and/or is planning to acquire any tattoos or body piercing during the period of the study. - Subjects with tattoos at the bilateral sites of needle insertion. - Pregnant or lactating women. Women of child bearing potential must be using effective contraception for at least 30 days prior to initial immunization, unless for religious, social, or medical reasons they do not intend to have children and are practicing sexual abstinence. Subjects using birth control must agree to do so for the entire 64 week study period. Acceptable method of birth control is defined as hormonal contraceptives, intrauterine device (IUD), diaphragm with spermicide, condoms, a vasectomized partner or abstinence. - Concomitant drug exclusion: corticosteroids (other than intranasal sprays or topical creams) or other known immunosuppressive drugs (such as chemotherapy for cancer); any experimental agent; any anti-tuberculosis medication, e.g., isoniazid (INH). - Personnel engaged in the blinding of this study. - Subjects who for any reason cannot adhere to the schedule of this protocol should not be enrolled in the study. - Subjects who in the judgment of the investigator would not be good candidates due to medical, psychiatric, or social conditions which may interfere with or serve as a contradiction to adherence to the study protocol. - Subjects with sex partners with known active Hepatitis B virus (HBV), HCV, or HIV infection. - Currently abuses alcohol. Alcohol abuse is defined as requiring hospital admission for detoxification and therapy or alcohol use that has had a significant impact on personal relationships or ability to work productively. - Not accessible by telephone or pager. - Live attenuated immunization within 4 weeks of each vaccination. - Inactivated immunization within 2 weeks of each vaccination. - Febrile illness within 3 days of study entry based on verbal report by the subject. | |
| 44 | NCT00618527 | completed | 1 | early phase 1 | ['multiple sclerosis'] | ["['G35', 'C81.18']"] | ['mycophenolate mofetil (cellcept)', 'human interferon beta 1a (rebif)'] | ['COC1=C(C\\C=C(/C)CCC(=O)OCCN2CCOCC2)C(O)=C2C(=O)OCC2=C1C', '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: - diagnosed with relapsing remitting multiple sclerosis - eligible to initiate interferon therapy - between he ages of 18-65, inclusive Exclusion Criteria: - have received corticosteroids within 30 days prior to study start - have ever received cyclophosphamide or mitoxantrone - have received Imuran or methotrexate in the last 3 months - females that are pregnant or breastfeeding are excluded | |
| 45 | NCT00630786 | completed | 1 | phase 1/phase 2 | ['colon cancer', 'colorectal cancer', 'rectal cancer', 'metastatic colorectal cancer', 'oncology'] | ["['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['panitumumab', 'conatumumab'] | ['NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F'] | Inclusion Criteria: - Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum - Radiographically documented disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) during or following treatment with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for Metastatic Colorectal Cancer. Progressive disease must be documented during or ≤ 6 months after the last dose of the most recent chemotherapy regimen prior to enrollment. - At least 1 uni-dimensionally measurable lesion measuring ≥ 20 mm in one dimension per modified RECIST. Lesion must not be chosen from a previously irradiated field, unless there has been documented disease progression in that field after irradiation and prior to enrollment. All sites of disease must be evaluated. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Available archived paraffin-embedded tumor tissue from the primary tumor or metastasis for submission to the central laboratory - Man or woman ≥ 18 years of age at the time of enrollment - Hematologic function within the following limits: - Absolute neutrophil count (ANC) > 1.0 x 10^9 cells/L - Platelets ≥ 100 x 10^9/L - Renal function within the following limits: - Creatinine < 2.0 mg/dL - Hepatic function within the following limits: - Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases) - Alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases) - Bilirubin ≤ 2 x ULN - Metabolic function within the following limits: - Amylase ≤ 2 x ULN - Lipase ≤ 2 x ULN - Magnesium ≥ lower limit of normal - Negative pregnancy test ≤ 72 hours before enrollment (for woman of childbearing potential only) - Must have received 1, 2, or 3 prior chemotherapy regimens for Metastatic Colorectal Cancer - Competent to comprehend, sign, and date the independent ethics committee/institutional review board (IEC/IRB) approved written informed consent Exclusion Criteria: - History of other primary cancer, unless: - Curatively resected non-melanomatous skin cancer - Curatively treated cervical carcinoma in situ - Other primary solid tumor curatively treated with no known active disease present and no treatment administered for ≥ 5 years before enrollment - Prior treatment with anti-epidermal growth factor receptor (EGFr) inhibitors (eg, cetuximab, erlotinib, gefitinib), unless treatment was received in the adjuvant setting ≥ 6 months before enrollment - Use of systemic chemotherapy and radiotherapy ≤ 30 days before enrollment - Use of prior anti-tumor therapies with a short serum half-life (less than 1 week) including prior experimental agents or approved anti-tumor small molecules ≤ 30 days before enrollment - Use of anti-tumor therapies with a longer serum half-life (eg, bevacizumab) including prior experimental or approved protein/antibodies ≤ 42 days before enrollment - Any investigational agent or therapy ≤ 30 days before enrollment - Known allergy or hypersensitivity to any component of panitumumab and/or AMG 655 - History of or known presence of central nervous system (CNS) metastases - History of interstitial lung disease (eg, pneumonitis, pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest computerized tomography (CT) scan - Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) ≤ 1 year before enrollment - Active inflammatory bowel disease or other active bowel disease causing chronic diarrhea (defined as ≥ Common Terminology Criteria for Adverse Events [CTCAE] grade 2 [CTCAE version 3.0]) - Known positive test for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic hepatitis B infection - Any co-morbid disease or condition that could increase the risk of toxicity (eg, significant ascites, significant pleural effusion) - Any uncontrolled concurrent illness (eg, infection, bleeding) or history of any medical condition that may interfere with the interpretation of the study results - Major surgical procedure (requiring general anesthesia) ≤ 28 days or minor surgical procedure (excluding central venous catheter placement) ≤ 14 days before enrollment. Patients must have recovered from surgery related toxicities. - Other investigational procedures are excluded - Patient is currently pregnant or breast feeding - Man or woman of childbearing potential who is not willing to use adequate contraceptive precautions during treatment and for 6 months (for women) or 1 month (for men) after the last investigational product administration. Adequate contraceptive precautions includes double barrier contraceptive methods (eg, diaphragm and condom) or abstinence. - Previously enrolled into this study - Patient unwilling or unable to comply with study requirements | |
| 46 | NCT00389285 | completed | 1 | phase 1/phase 2 | ['carcinoma, renal cell'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['ril-21 only', 'ril-21 + 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: - Diagnosis of RCC of predominantly clear cell histology - Either no prior treatment or a maximum of 2 prior treatment regimens for metastatic RCC that included no more than 1 treatment regimen targeting the vascular endothelial growth factor (VEGF) pathway (Phase 1 only) - At least 1 but no more than 2 prior systemic therapies for metastatic RCC that included no more than 1 therapy targeting the VEGF pathway (Phase 2 only) - Disease measurable per the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase 2 only) Exclusion Criteria: - Presence of acute infection or other significant systemic illness - Central nervous system involvement by malignancy - History of other cancer within 5 years - Previously received rIL-21 or sorafenib | |
| 47 | NCT00715403 | completed | 1 | phase 1 | ['neoplasms'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['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: 1. Male or female patients with advanced solid tumours who have completed a previous study with BIBF 1120. The patients should not have progression of their underlying tumour disease unless there is evidence for significant clinical benefit (e.g. symptom improvement) from treatment with BIBF 1120. 2. Age 18 years or older 3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance score <= 2 4. Patients must have given written informed consent (which must be consistent with ICH-GCP and local legislation) Exclusion Criteria: 1. Time elapsed from last administration of BIBF 1120 in the previous trial to start of treatment in the present trial exceeds four weeks 2. Presence of drug related toxicity > grade 2 CTC from previous therapy with BIBF 1120 or presence of drug related continuous toxicity of grade 2 for seven or more consecutive days which would preclude ongoing chronic therapy with BIBF 1120 3. Active ulcers (gastro-intestinal tract, skin) 4. Major injuries and surgery within the past three weeks with incomplete wound healing 5. Hypersensitivity to BIBF 1120 or the excipients of the trial drug 6. Known secondary malignancy requiring therapy 7. Active infectious disease 8. Significant cardiovascular diseases (i.e. uncontrolled severe hypertension, unstable angina pectoris, history of myocardial infarction, congestive heart failure > NYHA II) 9. Gastrointestinal disorders anticipated to interfere with the resorption of the study drug 10. Brain metastases requiring therapy 11. Absolute neutrophil count less than 1,500/mm3 12. Platelet count less than 100,000/mm3 13. Bilirubin greater than 1.5 mg/dl (> 26 µmol/L) 14. Aspartate amino transferase (AST) and/or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal) 15. Serum creatinine greater than 2 mg/dl (> 176 µmol/L) 16. Concomitant non-oncological diseases which are considered relevant for the evaluation of the safety of the trial drug 17. Chemo-, radio-, or immunotherapy within the past four weeks prior to treatment with the trial drug 18. Patients who are sexually active and unwilling to use a medically acceptable method of contraception 19. Pregnancy or lactation 20. Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy (visit 2) or concomitantly with this trial (except for a previous study with BIBF 1120) 21. Patients unable to comply with the protocol 22. Active alcohol or drug abuse | |
| 48 | NCT00598923 | terminated | end of funding and low enrollment | 0 | early phase 1 | ['traumatic brain injury', 'epilepsy'] | ["['Z87.820', 'Z13.850', 'S06.2X0S', 'S06.2X0A', 'S06.2X0D', 'S06.300S', 'S06.300A']", "['G40.803', 'G40.804', 'G40.911', 'G40.919', 'G40.B11', 'G40.B19', 'G40.801']"] | ['topiramate', 'topiramate', 'phenytoin'] | ['[H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2', '[H][C@@]12CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@@]3([H])[C@]1([H])OC(C)(C)O2', 'OC(=O)C1=CC=CC=C1O'] | Inclusion Criteria: 1. Moderate to severe traumatic brain injury, defined as one or more of the following: penetrating head wound seizure within the first hour after injury intracerebral hematoma or cortical contusion subdural or epidural hematoma Glasgow Coma Score <= 12 or motor score 1-5 (if intubated). Patients who have been pharmacologically paralyzed will be evaluated after the paralytic has worn off or been pharmacologically reversed depressed skull fracture requirement for emergent neurosurgical procedure 2. Time since TBI less than 24 hours 3. Age greater than or equal to 18 years 4. Subject capable of giving informed consent or have an acceptable surrogate capable of giving consent on the subject's behalf. - Exclusion Criteria: 1. Known prior history of epilepsy or unprovoked seizures. Patients with a history of acute symptomatic seizures (e.g. febrile seizure, alcohol withdrawal seizure) will not be excluded 2. Administration of an antiepileptic drug before enrollment 3. History of allergy to topiramate or phenytoin 4. Pregnancy or breast-feeding. Women of childbearing potential must have a negative pregnancy test (urine pregnancy test or serum beta-HCG) before randomization 5. Compromised renal function with serum creatinine > 2 6. Severe concurrent illness with life expectancy <6 months 7. Treatment with another investigational agent for TBI 8. Unable to take medications orally and contraindication to placement of nasogastric tube. 9. Irreversibly fatal TBI 1. All four findings: Glasgow Coma Score = 3, no pupillary reaction, age > 45 years, and severe coagulopathy OR 2. Severe brainstem lesion on neuroimaging studies 10. Patients with a history of kidney stones or glaucoma. 11. Inability to maintain adequate fluid intake while taking topiramate. 12. Patients whose TBI is a result of self inflicted injury 13. Patient's who are currently using illicit drugs - |
| 49 | NCT01353534 | completed | 1 | phase 1/phase 2 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['vaccine enhancement patch'] | ['[O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O'] | Inclusion Criteria: - Healthy adult males or females 18-49 years of age (inclusive) - signed Informed Consent - Women who are not post-menopausal or surgically sterile must have a negative serum or urine pregnancy test at screening and at all in-clinic visits with understanding to not become pregnant over the duration of the study. Exclusion Criteria: - Clinically significant laboratory abnormalities at screening - abnormalities at physical examination - known allergies to any component of the A/H5N1 antigen - known egg protein allergy - known allergies to adhesives - known coagulation disorders - use of any anticoagulant medication within 30 days prior to vaccination or planned usage during the study period - participated in research involving investigational product within 30 days before planned date of vaccination or planned participation during study period - donated or received blood or blood products such as plasma within the three months before planned date of vaccination or planned donation or use during the study period - received or planned receipt of seasonal influenza vaccine during the study period - received any licensed vaccines within 2 weeks (inactivated vaccines) or 4 weeks (live vaccines) prior to planned date of vaccination - planned receipt of any licensed vaccine during the first 42 days on study - previous or planned vaccination with any vaccine containing an oil in water emulsion adjuvant - previous or planned vaccination with pandemic vaccine against A/H5N1 or previous proven contact with A/H5N1 wild type virus - ever received investigational enterotoxigenic E. coli LT, or LT (R192G) or NasalFlu, Berna Biotech, Ltd. Ever received cholera toxin or vaccine - Recent or regular use of oral, topical or injected steroid medications within 30 days prior to vaccination or planned use during the study period. - Use of immunosuppressive systemic steroid medications including inhaled steroids within three months prior to vaccination or planned use during the study period - Comorbid conditions or treatments that are immunosuppressive, including cancer, diabetes, and end-stage renal disease, as determined by the Investigator - positive serology for HIV-1, HIV-2, HBsAg, or HCV - history of severe atopy - medical history of acute or chronic skin disease at vaccination area - active skin allergy - signs of acute skin infection, sunburn or skin abnormalities at the vaccination area including fungal infections, severe acne, active contact dermatitis, or a history of keloid formation - hirsute at vaccination area - artificial tanning over the duration of the study including the screening period - visible tattoos or marks at the vaccination area that would prevent appropriate dermatologic monitoring of the vaccination site - fever greater than or equal to 38.0°C at the time of planned vaccination - suspicion of or recent history of alcohol or substance abuse - women who are pregnant or breastfeeding - acute illness at screening or at the time of planned vaccination - ever had a serious reaction to prior influenza vaccination - developed a neurological disorder following a previous influenza vaccination or have any acute and evolving neurological disorder - employee of the investigational site or sponsor - history of employment in bird or poultry industries or considerable exposure to birds | |
| 50 | NCT00256334 | completed | 0 | phase 1 | ['colon cancer', 'cancer'] | ["['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['resveratrol'] | ['OC1=CC=C(\\C=C\\C2=CC(O)=CC(O)=C2)C=C1'] | Inclusion Criteria: - Patients diagnosed with colon cancer by colonoscopic biopsy and tissue obtained under UCI04-05. - Patients with a plan for surgical resection at UCIMC within 2-4 weeks of enrollment. Exclusion Criteria: - Surgical resection to be performed at a facility other than UCIMC. - Patients under 18 years of age. | |
| 51 | NCT01154335 | completed | 1 | phase 1 | ['metastatic colorectal cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['osi-906', 'everolimus'] | ['C[C@@]1(O)C[C@@H](C1)C1=NC(=C2N1C=CN=C2N)C1=CC=C2C=CC(=NC2=C1)C1=CC=CC=C1', '[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: - Metastatic cancer of the colon or rectum that has progressed on or for which the patient is intolerant to or not a candidate for: fluoropyrimidines, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. - Testing for Kras mutation performed;Patients with mutated or wild type Kras are eligible. - ECOG PS of 0-1 - Life expectancy of ≥ 3 months - Adequate hematological function with ANC 1500, Platelets of 100,000, and hemoglobin of 9.0 - AST, ALT and Alk. Phos. ≤2.5 x ULN or ≤5 x ULN if known hepatic metastases and a total bilirubin ≤1.5 ULN - Serum creatinine of ≤1.5 x ULN - Fasting blood glucose <150 mg/dL - Measurable disease according to RECIST 1.1 - Able to swallow whole pills - INR ≤1.5 - Anticoagulation is allowed with LMW heparin - Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN;If these thresholds are exceeded, the patient can be included after initiation of lipid lowering medication Exclusion Criteria: - Patients who have received any cancer therapies <4 weeks or 5 half lives (whichever is shorter) of initiating study therapy - Treatment with any investigational drug ≤ 4 weeks, or 5 half-lives of the drug, whichever is shorter - Patients who require coumadin for anticoagulation - Patients who have had major surgery or significant traumatic injury ≤4 weeks of the of study treatment - Minor surgery (with the exception of port placement) must be completed ≤ 7days prior to study therapy - Previous treatment with an IGFR inhibitor or MTOR Inhibitor - Chronic, systemic treatment with corticosteroids or another immunosuppressive agent - Patients with QTc interval >450ms - Patients who require drugs that can prolong QTc. - Patients with congenital long QT syndrome, history of ventricular tachycardia, or ventricular fibrillation, or Torsades de Pointes with bradycardia. - Immunization with attenuated live vaccines within 1 week of beginning study therapy or during study period;Close contact to anyone that has received live virus vaccine should be avoided - Meningeal or brain metastasis - Other malignancies < 3 years, with the exception of adequately treated basal or squamous cell carcinomas of the skin, or carcinoma in situ of the cervix - Patients with known HIV - Patients with positive testing for hepatitis B or C - Patients with risk factors for hepatitis must be tested for hepatitis viral loadHepatitis risk factors include the following: Lived in Asia, Africa, Central and South America, Eastern Europe, Spain, Portugal, and Greece Any blood transfusions before 1990 Any IV drug use Any dialysis Household contact with a Hep B infected patient Mother had Hep B High-risk sexual activity Body piercing/tattoos - History suggestive of hepatitis B - Any severe or uncontrolled conditions that could affect their study participation such as:Severely impaired lung function;DCLO ≤ 50% of normal predicted value;O² Sat <88% at rest on room air - Congestive Heart Failure of NYHA Class III or IV - Unstable angina, symptomatic CHF, MI ≤ 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant heart disease - CVA, TIA, angioplasty, or cardiac stenting <12 months - Ventricular arrhythmia requiring medication - Known history of diabetes and/or patients who require ongoing use of insulin or oral anti-hyperglycemic therapy - Known liver disease - Impairment of GI function or gastrointestinal disease that in may significantly alter the absorption of study drugs - Concurrent treatment with drugs that are strong CYP3A4 inducers or moderate/strong CYP3A4 inhibitors - Concurrent treatment with drugs that are strong CYP1A2 inhibitors or inducers Women who are pregnant or breastfeeding. - Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements | |
| 52 | NCT01227239 | unknown status | 0 | phase 1/phase 2 | ['rectal carcinoma'] | ["['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['s-1', 'oxaliplatin'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: 1. Patients with confirmed locally advanced and non-metastatic rectal adenocarcinoma (clinical stage T3, anyN or T4, anyN) 2. Possible to R0 resection 3. Received no prior therapy 4. Performance status (ECOG) 0-1 5. Normal organ and marrow function. 6. Sufficient oral intake Exclusion Criteria: 1. History of serious allergic reaction 2. Patients without serious complications such as sensory neurotoxicity or serious diarrhea (with watery stool). 3. Female with pregnancy or lactation 4. Have another malignancy in the past 5 years except early stage other cancer that cure by local treatment | |
| 53 | NCT01623466 | completed | 0 | phase 1/phase 2 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['levonorgestrel'] | ['[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]'] | Inclusion Criteria: - Body mass index (BMI) greater than or equal to 18. - Willing to use a non-hormonal method of contraception if of childbearing potential, or have already undergone previous bilateral tubal ligation or hysterectomy - Willing to refrain from excessive use of alcohol from 48 hours prior to patch application through completion of the study. Exclusion Criteria: - Known or suspected pregnancy - Lactating women - Status post-partum or post-abortion within a period of 2 months prior to the start of study medication - A cervical cytology smear of Papanicolaou (Pap) class III or greater or a Bethesda System report of low grade squamous intraepithelial lesions (SIL) or greater - Smoking - Hypertension (blood pressure >140 mm Hg systolic and/or >90 mm Hg diastolic) - Valvular heart disease with complications - ECG (in women with BMI ≥35 kg/m2) with clinically significant findings - Diabetes Mellitus - History of headaches with focal neurological symptoms - Uncontrolled thyroid disorder - Sickle cell anemia - Current or history of clinically significant depression in the last year - Known disturbance of lipid metabolism - Acute or chronic hepatocellular disease with abnormal liver function - Hepatic adenoma or carcinoma - Cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use - Plans for major surgery - History of or existing venous and arterial thrombotic and thromboembolic disorder, vascular disease, cerebral vascular, or coronary artery disease - Undiagnosed abnormal genital bleeding - Known or suspected breast carcinoma, endometrial carcinoma, or estrogen-dependent neoplasia - History or presence of dermal hypersensitivity in response to topical applications (bandages, surgical tape, etc.) - Use of an injectable hormonal contraceptive within the past 10 months prior to the screening visit - Use of a contraceptive implant or hormone-medicated intrauterine device (IUD) within 1 month prior to the screening visit - Use of oral contraceptives or other sex steroid hormones within 2 months prior to the screening visit - Chronic use of any medication that might interfere with the efficacy of hormone contraceptives (including barbiturates, bosentan, carbamazepine, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, St. John's Wort, topiramate, and HIV protease inhibitors), OR use of these medications within the past 3 months prior to screening visit - A recent history (within prior 2 years ) of drug or alcohol abuse | |
| 54 | NCT00329004 | completed | 1 | phase 1 | ['cancer', 'tumor'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['E88.3', 'R97.8', 'C49.A0', 'C49.A1', 'C49.A2', 'C49.A5', 'C49.A3']"] | ['bms-690514'] | ['COC1=CC=CC(NC2=NC=NN3C=CC(CN4CC[C@@H](N)[C@H](O)C4)=C23)=C1'] | Inclusion Criteria: - Men and women 18 and older - Diagnosis of any solid tumor - ECOG performance status score 0-1 - Prior chemo-therapy, immunotherapy or radiotherapy with at least 4 weeks since the last treatment - Treatment with VEGFR2 or HER1 TKI allowed but not both (for instance Avastin or Tarceva, but not both) Exclusion Criteria: - Treatment with other TKIs within the past 4 weeks - Patients with brain metastasis - Patients with centrally located squamous cell carcinoma of the lung - Major gastrointestinal surgery which may affect absorption of the drug - Any surgery within last 4 weeks - History of thromboembolism - Severe unmanageable diarrhea - Subjects in Part B will have Non-Small Cell Lung Cancer (NSCLC) - Part B/Cohort I erlotinib-naive subjects - Part B/Cohort II subjects who have experienced disease progression while receiving erlotinib (erlotinib-resistant subjects) | |
| 55 | NCT01107899 | terminated | terminated due to enrollment futility | 0 | phase 1 | ['acute coronary syndromes'] | ["['I24.0']"] | ['clopidogrel', 'prasugrel'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'CC(=O)OC1=CC2=C(CCN(C2)C(C(=O)C2CC2)C2=CC=CC=C2F)S1'] | Inclusion Criteria: - Men or women ≥18 to <80 years of age who present with any one of the following: - symptoms of Acute Coronary Syndromes (ACS) - clinical symptoms of angina, or a positive stress test or who return for routine follow up angiography post stent placement in whom co-administration of aspirin and a thienopyridine (that is, clopidogrel, ticlopidine, or prasugrel) is not contraindicated Exclusion Criteria: - Those presenting with ST-elevation MI (STEMI) - histories of refractory ventricular arrhythmias - an implanted defibrillator device - congestive heart failure (NYHA Class III or above) within 6 months prior to screening - significant hypertension - subjects with a history or clinical suspicion of cerebral vascular malformations, transient ischaemic attack, or stroke - bleeding disorders - women known to be pregnant, who have given birth within the past 90 days, or who are breastfeeding |
| 56 | NCT01463982 | completed | 1 | phase 1 | ['solid tumor', 'advanced cancer'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']"] | ['oratecan and capecitabine'] | ['CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O'] | Inclusion Criteria: - Histologically or cytologically confirmed advanced solid tumor - Patients who have experienced progressive disease despite of conventional anticancer therapy. Patients who cannot expect effective treatment or prolonged survival with conventional anticancer therapy - Previous chemotherapy, radiotherapy and surgical operation are allowed if they are discontinued for at least 4 weeks prior to D0 and all adverse events are resolved - Aged ≥19 - Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2 - A life expectancy greater than 12 weeks - Adequate bone marrow, renal and liver function. - Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures Exclusion Criteria: - Patients with hematopoietic malignancies,uncontrolled infection, CNS metastasis. - Patients who have undergone hematopoietic stem cell transplantation (HSCT) or are candidates for planned HSCT - Patients who have GI malabsorption or difficulty taking oral medication - Patients who have psychiatric or congenital disorder Subjects who, in the investigator's opinion, cannot be treated per protocol due to functional impairments - Pregnant or breast-feeding patients; Women of childbearing potential without adequate contraception (Men must use adequate contraception.) | |
| 57 | NCT01296568 | completed | 0 | phase 1 | ['advanced cancer'] | ["['K74.02', 'G47.22', 'H35.3133', 'H35.3134', 'H35.3113', 'H35.3114', 'H35.3123']"] | ['ly2603618', 'pemetrexed', 'gemcitabine'] | ['CC1=NC=C(NC(=O)NC2=C(OC[C@@H]3CNCCO3)C=C(C)C(Br)=C2)N=C1', '[H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H]', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Have a histological or cytological diagnosis of cancer (solid tumor), with clinical or radiologic evidence of locally advanced and/or metastatic disease, for which no life-prolonging therapy exists (that is, refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists). Note: participants who have had progressive disease after receiving pemetrexed for metastatic disease are excluded from receiving the combination with pemetrexed during the safety extension study. Participants who have had progressive disease after receiving gemcitabine for metastatic disease are excluded from receiving the combination with gemcitabine during the safety extension study. - Have a body surface area greater than or equal to 1.37 meters squared (m^2) - Have given written informed consent prior to any study-specific procedures - Adequate hematologic, hepatic and renal function - Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale - Have discontinued all previous treatments for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy, or other investigational therapy for at least 30 days prior to study entry and recovered from the acute effects of therapy (at least 42 days for mitomycin-C or nitrosoureas, or 60 days for monoclonal antibodies) - Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedure - Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and following the last dose of study drug until, in the judgment of the investigator, it is safe for the participant to become pregnant or father a child - Females with childbearing potential: Have had a negative serum pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding - Have an estimated life expectancy that, in the judgment of the investigator, will permit the participant to complete 1 full cycle of treatment (beyond the initial [^14C]LY2603618 dose) - Prior radiation therapy for treatment of cancer other than pancreatic is allowed to <25% of the bone marrow and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry. Exclusion Criteria: - Have received treatment within 28 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication - Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other checkpoint kinase one (Chk1) inhibitor - Have a known allergy to gemcitabine, pemetrexed, LY2603618, or any ingredient of gemcitabine, pemetrexed, or LY2603618 (like Captisol) - Have serious preexisting medical conditions (left to the discretion of the investigator) other than advanced cancer - Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 90 days - Have current hematologic malignancies or either acute or chronic leukemia - Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required) - Have a QTc interval of >500 milliseconds (msec) on the screening electrocardiogram (ECG) - Have ECG abnormalities on the screening ECG such as significant conduction abnormalities, ischemic changes (such as prior Q-wave myocardial infarction and/or marked ischemic ST- and T-wave), arrhythmias (such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation), or other ECG abnormalities that would put the participant at unnecessary risk in the opinion of the investigator - Have participated in a ^14C study within the last 6 months prior to screening for this study. The total exposure from this study and the previous study must be less than 5 milliSieverts (mSv). | |
| 58 | NCT01028781 | terminated | difficulty finding eligible participants and lack of funding. | 0 | phase 1 | ['endometriosis'] | ["['N80.8', 'N80.9', 'N80.0', 'N80.1', 'N80.5', 'N80.2', 'N80.3']"] | ['thalidomide'] | ['CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2'] | Inclusion Criteria: 1. Age > 18 years 2. Histologically/laparoscopically confirmed endometriosis 3. Chronic pelvic pain defined as non-menstrual pain for at least two weeks in the previous month for at least 6 months 4. VAS of 6 or more at baseline 5. Failure, completion or intolerance of standard treatment modalities (oral contraceptive therapy, danazol, Depo-Provera, Depo-Lupron) 6. Patients must give written informed consent. 7. Patients must be willing and able to comply with the FDA-mandated S.T.E.P.S.® program. Exclusion Criteria: 1. Pregnant and/or lactating female 2. Users of other angiogenesis inhibitors 3. Current use of Rifampin, rifabutin, barbiturates, glucocorticoids, phenytoin, carbamazepine, chlorpromazine, reserpine, penicillin derivatives, or St. Johns Wart in user of oral contraceptive therapy 4. Use of aromatase inhibitors, Etanercept (Enbrel), GnRH agonists (Depo-Lupron), and Danazol within the past 3 months 5. Use of norethindrone acetate (Aygestin) in the prior month 6. Seizure disorder 7. Hepatitis, or any active infection (upper respiratory infection, PID, etc) 8. History of thromboembolic disease. 9. Baseline neutropenia (ANC < 1000/mm^3) 10. Any severe physical or metal illness that would interfere with the completion of the protocol 11. Illicit drug or alcohol abuse |
| 59 | NCT00062127 | completed | 0 | phase 1 | ['unspecified adult solid tumor, protocol specific'] | ["['H01.009', 'H02.209', 'H02.009', 'H02.109', 'H04.209', 'H05.409', 'H10.509']"] | ['irinotecan hydrochloride', 'thalidomide'] | ['CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=CC=C(OC(=O)N3CCC(CC3)N3CCCCC3)C=C12', 'CC(C)NCC(O)COC1=CC=CC2=C1C=CC=C2'] | Inclusion Criteria: - Histologically confirmed malignant solid tumor - Metastatic or unresectable - Standard curative or palliative therapy is no longer effective or does not exist - Measurable or assessable disease - No uncontrolled brain metastases - Patients with brain metastases are eligible provided the following are true: - Stable neurologic status - At least 4 weeks since prior steroids or anticonvulsants - No neurologic dysfunction that would confound evaluation - Performance status - Karnofsky 70-100% - More than 12 weeks - WBC at least 3,000/mm^3 - Absolute neutrophil count at least 1,500/mm^3 - Platelet count at least 100,000/mm^3 - Bilirubin normal - AST and ALT no greater than 2.5 times upper limit of normal - Creatinine normal - Creatinine clearance at least 60 mL/min - No symptomatic congestive heart failure - No unstable angina pectoris - No cardiac arrhythmia - No history of inflammatory bowel disease requiring therapy - No chronic diarrhea syndromes - No paralytic ileus - Not pregnant or nursing - Negative pregnancy test - Fertile female patients must use 2 forms of effective contraception, including 1 highly effective method, for at least 4 weeks before, during, and for 4 weeks after study participation - Male patients must use effective barrier contraception during and for 4 weeks after study participation - No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs - No uncontrolled seizure disorder - No other concurrent uncontrolled illness that would preclude study participation - No psychiatric illness or social situation that would preclude study compliance - No ongoing or active infection - No significant traumatic injury within the past 28 days - No serious, nonhealing wounds or ulcers - No bone fractures - No preexisting peripheral neuropathy grade 2 or greater - At least 4 weeks since prior biologic therapy - At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) - See Disease Characteristics - At least 4 weeks since prior radiotherapy - More than 28 days since prior major surgical procedure or open biopsy - At least 4 weeks since prior investigational therapy - No concurrent combination antiretroviral therapy for HIV-positive patients - No other concurrent investigational or commercial agents or therapies for the malignancy | |
| 60 | NCT01474161 | completed | 1 | phase 1 | ['type 2 diabetes', 'diabetes mellitus, type 2', 'metabolic diseases', 'cardiovascular diseases', 'obese', 'dyslipidemia'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']", "['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']", "['Z86.39', 'O99.280', 'O99.281', 'O99.282', 'O99.283', 'O99.284', 'O99.285']", "['A52.00', 'A52.09', 'A50.54', 'Z01.810', 'Q87.418', 'Z13.6', 'R94.30']"] | ['gft505 120mg - old formulation', 'gft505 120mg - new formulation', 'gft505 180mg - new formulation', 'gft505 240mg - new formulation', 'gft505 300mg - new formulation', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: Part I : - Male or female healthy volunteers 18 to 45 years of age (inclusive). - Subjects with a body mass index (BMI) ≥ 18 and ≤ 28 kg/m2 at screening. - For female subjects of childbearing potential, use of double contraception method. - Normal arterial blood pressure (BP) and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator. Part II and III : - Male healthy volunteers 18 to 55 years of age (inclusive). - Subjects with a BMI >28 and <35 kg/m2 at screening. - Normal arterial BP and pulse rate or, if abnormal, considered not clinically significant by the principal Investigator. Part IV : - Male or female Type 2 diabetic patients 18 to 60 years of age. - Females participating in the study must be either of non-child bearing potential or using an efficient double contraception. - Currently treated with any antidiabetic treatment (a maximum of two anti-diabetic drugs including metformin in all cases) with the exception of insulin or GLP analogs and agonists therapy. - Stable diabetes with glycosylated hemoglobin (HbA1c) < or =10% or less. - Normal renal function as defined by a creatine clearance >90 mL/min calculated with the Cockcroft-Gault formula. - Subjects with a BMI from 18 to 32 kg/m2 at screening. Exclusion Criteria: Part I : - Who previously received GFT505. - With any clinically significant abnormality following review of prestudy laboratory tests (Aspartate and Alanine aminotransferase must be within normal ranges), vital signs, full physical examination and Electrocardiogram. - Who have a positive laboratory test for Hepatitis B surface antigen (HbsAg), or anti-HIV 1/2 (Human immunodeficiency virus) or anti-HCV (Hepatitis C virus) antibodies. - Who are known or suspected alcohol or drug abusers (more than 14 units of alcohol per week, one unit = 8 g or about 10 mL of pure alcohol). - Who drink more than 8 cups daily of beverage containing caffeine. - Who have a positive laboratory test for urine drug screening (opiates, cocaine, amphetamine, cannabis, benzodiazepines). - Who have undergone surgery or have donated blood within 12 weeks prior to the start of the study. - Who have taken any prescribed or over the counter drug (including antacid drug), with the exception of paracetamol (up to 3 g per day) within 2 weeks prior to the first dose administration. Part II and III : specific additional exclusion criteria - Who have taken fibrates within 6 weeks prior to the first dose administration. Part IV : specific additional exclusion criteria - With unstable proliferative retinopathy, macular oedema (fundus examination performed in the previous year will be considered relevant on Investigator's judgement). - Who have taken fibrates within 6 weeks prior to the first dose administration. | |
| 61 | NCT00703807 | completed | 1 | phase 1 | ['endometrial cancer'] | ["['N85.00', 'N85.01', 'N85.02', 'N99.85']"] | ['topotecan', 'rad001'] | ['CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=C(C=CC(O)=C4CN(C)C)N=C13)C2=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](O)[C@@H](C1)OC'] | Inclusion Criteria: - Patients must have histologically-confirmed advanced or recurrent endometrial cancer - Patients must be refractory to standard therapy or for which no curative standard therapy exists, to be considered. Metastatic disease, if present, should not be progressing so as to require palliative treatment within 4 weeks of enrollment based on clinical assessment by the investigator. - Development of new lesions or an increase in preexisting lesions on bone scintigraphy, CT, MRI or by physical examination. Patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible. - Age ≥ 18 years - WHO performance status ≤ 2 - Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL - Adequate liver function as shown by: - serum bilirubin ≤ 1.5 x ULN - INR < 1.3 (or < 3 on anticoagulants) - ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases) - Adequate renal function: serum creatinine ≤ 1.5 x mg/dL - Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. - Signed informed consent Exclusion Criteria: - Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.) - Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study - Prior treatment with any investigational drug within the preceding 4 weeks - Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with RAD001. Topical or inhaled corticosteroids are allowed. - Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period - Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases - Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. - Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: - Symptomatic congestive heart failure of New York heart Association Class III or IV - unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease - severely impaired lung function - uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN - active (acute or chronic) or uncontrolled severe infections - liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis - A known history of HIV seropositivity - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) - Patients with an active, bleeding diathesis - Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001) - Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus). - Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients - History of noncompliance to medical regimens - Patients unwilling to or unable to comply with the protocol | |
| 62 | NCT00463697 | completed | 1 | phase 1 | ['pulmonary disease, chronic obstructive'] | ["['J44.9', 'J44.1', 'J44.0']"] | ['gw642444h (100mcg)', 'placebo', 'gw642444m (25, 100 & 400 mcg)'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'OCC1=C(O)C=CC(=C1)[C@@H](O)CNCCCCCCOCCOCC1=C(Cl)C=CC=C1Cl'] | Inclusion criteria: - male or female (of non-childbearing potential) between 18 - 70 years - History of stable mild to moderate asthma - non - smokers - currently taking daily doses of inhaled fluticasone propionate 200 - 500 mcg (or equivalent) - body weight >50 kg with BMI 19-29.9 kg/m2 - normal ECG assessment Exclusion criteria: - history of significant disease - history of life threatening asthma - recent respiratory tract infection - recent change of asthma medication - treatment with high dose inhaled corticosteroids or oral corticosteroids - recent participation in another trial - history of drug or alcohol abuse - known allergies (excluding asthma) - recent blood donation | |
| 63 | NCT00098514 | completed | 0 | phase 1 | ['unspecified adult solid tumor, protocol specific'] | ["['H01.009', 'H02.209', 'H02.009', 'H02.109', 'H04.209', 'H05.409', 'H10.509']"] | ['talotrexin ammonium'] | ['NC1=NC(N)=C2N=C(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCCNC(=O)C3=CC=CC=C3C(O)=O)C(O)=O)C=NC2=N1'] | DISEASE CHARACTERISTICS: - Diagnosis of malignant solid tumor - Metastatic or inoperable disease - No known curative or survival-prolonging palliative therapy exists OR failed these prior therapies - No leukemia - No primary CNS tumor - No third-space fluid collection (i.e., pleural effusion, ascites) - Clinically insignificant small pleural or peritoneal effusions identified by CT scan, MRI, or other diagnostic test allowed - No active* brain metastases, including the following: - Evidence of cerebral edema by CT scan or MRI - Progression since prior imaging study - Requirement for steroids - Clinical symptoms of/from brain metastases NOTE: *Treated and/or stable brain metastasis allowed provided patient is asymptomatic PATIENT CHARACTERISTICS: Age - 18 and over Performance status - ECOG 0-2 Life expectancy - At least 2 months Hematopoietic - Absolute neutrophil count ≥ 1,500/mm^3 - Platelet count ≥ 100,000/mm^3 - RBC folate ≥ lower limit of normal Hepatic - Bilirubin normal - SGOT and SGPT ≤ 2.5 times upper limit of normal Renal - Creatinine clearance ≥ 50 mL/min Other - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No other uncontrolled serious medical or psychiatric illness PRIOR CONCURRENT THERAPY: Biologic therapy - No prior bone marrow transplantation Chemotherapy - More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) Endocrine therapy - See Disease Characteristics Radiotherapy - More than 3 weeks since prior radiotherapy - No concurrent radiotherapy Surgery - At least 3 weeks since prior surgery Other - Recovered from prior therapy - More than 3 weeks since prior antifolate therapy | |
| 64 | NCT00147875 | completed | 1 | phase 1/phase 2 | ["hodgkin's disease"] | ["['C81.77', 'C81.97', 'C81.17', 'C81.27', 'C81.37', 'C81.47', 'C81.70']"] | ['prednisone', 'vinblastine', 'doxorubicin (adriamycin)', 'gemcitabine'] | ['[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', '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', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Hodgkin's lymphoma (histologically proven) - Clinical stage IIB (with risk factors bulky mediastinal mass and/or extranodal involvement), III, or IV - No prior antitumor therapy - Age 60 to 75 years - WHO performance status 0-2 - Normal pulmonary function - Written informed consent Exclusion Criteria: - The following histologies are excluded: lymphocyte predominant HD - Leukocytes < 2,500/microL - Platelets < 100,000/microL | |
| 65 | NCT01350258 | terminated | poor accrual | 0 | phase 1/phase 2 | ['hematologic malignancies', 'acute leukemia', 'myelodysplastic syndromes (mds) other than ra or rars subtypes', "hodgkin's lymphoma", "non-hodgkin's lymphoma", 'myeloma', 'chronic myelogenous (or myeloid) leukemia (cml) resistant to sti therapy'] | ["['E70.338', 'E70.339', 'P09.3', 'O28.0', 'P61.8', 'P61.9', 'T45.8X1A']", "['C91.01', 'C91.02', 'C92.01', 'C92.02', 'C92.41', 'C92.42', 'C92.51']", "['D46.Z', 'D46.9', 'C94.6', 'D46.C']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['S33.110S', 'S33.111S', 'S33.120S', 'S33.121S', 'S33.130S', 'S33.131S', 'S33.140S']", "['C90.01', 'C90.02', 'C90.00']", "['Z19.2', 'A41.02', 'A49.02', 'J15.212', 'Z86.14', 'Z22.322', 'B95.62']"] | ['fludarabine', 'thiotepa', 'melphalan'] | ['ClCCN(CCCl)P1(=O)NCCCO1', 'CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1', 'N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O'] | Inclusion Criteria: 1. Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as: - Acute leukemia in 3rd or greater CR or with persistent disease - Myelodysplastic syndrome (MDS) other than RA or RARS subtypes. - Hodgkin's or Non-Hodgkin's lymphoma in 3rd or greater remission or with persistent disease. - Myeloma in 3rd or greater remission or with less than PR to most recent therapy. - Chronic myelogenous (or myeloid) leukemia (CML) resistant to STI therapy 2. Patients must have a related donor who is at least a 4 antigen match at the HLA-A; B; C; DR loci. 3. Patients must adequate organ function: - LVEF of > or = 50% - DLCO > or = 50% of predicted corrected for hemoglobin - Adequate liver function as defined by a serum bilirubin < or = 1.8, AST or ALT < or = 2.5X upper limit of normal - GFR of > or = 60 mL/min/1.73m2 4. Performance status > or = 80% (TJU Karnofsky) for patients > or = 60 years old or > or = 70% for patients < 60. 5. HCT-CI Score < or = 4 points for patients > or = 60 years old or < or = 5 points for patients < 60. 6. Patients must be willing to use contraception if they have childbearing potential 7. Able to give informed consent Exclusion Criteria: 1. Performance status < 80% (TJU Karnofsky) for patients > or = 60 years old or < 70% for patients < 60. 2. HCT-CI Score > 4 points for patients > or = 60 years old or > 5 points for patients < 60. 3. HIV positive 4. Active involvement of the central nervous system with malignancy 5. Inability to obtain informed consent 6. Pregnancy 7. Patients with life expectancy of < 6 months for reasons other than their underlying hematologic/oncologic disorder 8. Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of > or = 2 ugm/ml 9. Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol Donor Selection All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences. Donor selection will be in compliance with 21 CFR 1271 and TJU BMT Program SOP CP: P009.03. |
| 66 | NCT01046630 | completed | 1 | phase 1 | ['depression'] | ["['F32.A', 'F53.0', 'P91.4', 'Z13.31', 'Z13.32']"] | ['azd6765', 'ketamine', 'placebo'] | ['N[C@@H](CC1=CC=CC=N1)C1=CC=CC=C1', 'CC1=CC(O)=CC(C)=C1Cl', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Documented clinical diagnosis meeting criteria from the DSM-IV by structured clinical interview,major depressive disorder, single episode or recurrent - Outpatient status at screening and at randomisation Exclusion Criteria: - A major depression disorder which has a major impact on the subjects current psychiatric status - Subjects not allowed to use mood stabilizers, antidepressants or other antipsychotic or psychoactive drugs - Subjects with lifetime history of schizophrenia, bi-polar, psychosis and psychotic depression | |
| 67 | NCT01003678 | terminated | drug provider withdrew support | 0 | phase 1 | ['myelodysplastic syndrome'] | ["['D46.9', 'D46.C', 'D46.Z']"] | ['clofarabine'] | ['[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: - Provide signed written informed consent. - Patients with MDS must have IPSS score that falls in the intermediate or high risk disease (intermediate 1 will have to be transfusion dependent). - Patients may have received up to two prior therapies for MDS including one hypomethylating agent and/or a biologic agent (biologic agents include GM-CSF or equivalent, danazol or equivalent, Sunitinib, Revlimid, ATG, or a vaccine). - Age ≥ 18 - Have adequate renal and hepatic functions as indicated by the following laboratory values: - Serum creatinine ≤ 1 mg/dL; if serum creatinine >l mg/dL, then the estimated glomerular filtration rate (GFR) must be >50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation. - Serum bilirubin ≤1.5 mg/dL x upper limit of normal (ULN) - Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x ULN - Alkaline phosphatase ≤2.5 x ULN - Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. - Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment. - Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. Exclusion Criteria: - Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment. - Active CNS disease - Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). - Pregnant or lactating patients. - Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. - Have had any prior treatment with clofarabine - Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy, with the following exceptions: - Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. - Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed. - Have prior positive test for the Human Immunodeficiency Virus (HN). - Have prior positive test for the Human Immunodeficiency Virus (HN). - Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine. - Patients taking proton pump inhibitors such as omeprazole (Prilosec®), lansoprazole (Prevacid®), or esomeprazole (Nexium®). Those who cannot stop taking these drugs should be switched to H2 blockers such as famotidine (Pepcid®)or ranitidine (Zantac®). - Patients taking alternative medicines (such as herbal or botanical) are not permitted. |
| 68 | NCT01405963 | completed | 1 | phase 1 | ['asthma'] | ["['J45.998', 'J82.83', 'J45.909', 'J45.991', 'J45.20', 'J45.30', 'J45.40']"] | ['amg 157 matching placebo', 'amg 157'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Male or female subjects with history of mild atopic asthma between 18 and 60 years-of-age - Body mass index (BMI) between 18 and 35 kg/m2 - Normal or clinically acceptable physical examination (PE), clinical laboratory values, and ECG; clinically acceptable PE includes history of mild atopic asthma - Used only inhaled short-acting β2-agonists infrequently to treat asthma - No current exposure to allergens to which subject experiences asthmatic responses - No other lung disease, exacerbations of asthma or lower respiratory tract infections for at least 6 weeks prior to screening - Positive skin prick test to common aeroallergens at screening - Additional inclusion criteria apply Exclusion Criteria: - History or evidence of a clinically significant disorder (including psychiatric), condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion; - History or current medical conditions that are contraindicated for methacholine challenge, such as myocardial infarction or stroke within previous 3 months, known cardiac disease, uncontrolled hypertension and aortic or cerebral aneurysm - Evidence of active or suspected bacterial, viral, fungal or parasitic infections within past 6 weeks - Subject has know type I/II diabetes - History of residential exposure to tuberculosis or has a positive PPD or QuantiFERON test within 4 weeks before randomization - Subject who has history of malignancy of any type within 5 years prior to enrollment - Subjects tested positive for drugs/alcohol or nicotine use at screening - Subjects tested positive for HIV, Hep B or Hep C - Additional exclusion criteria apply | |
| 69 | NCT00529100 | completed | 1 | phase 1/phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['pemetrexed phase 1', 'cisplatin phase 1', 'pemetrexed phase 2', 'cisplatin phase 2'] | ['[H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(CCC2=CNC3=C2C(O)=NC(=N)N3)C=C1)C(O)=O', '[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', '[H][C@@](CCC(O)=O)(NC(=O)C1=CC=C(CCC2=CNC3=C2C(O)=NC(=N)N3)C=C1)C(O)=O', '[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: Some of the requirements to be in this study are: - Patient must be at least 18 years old. - Patient must have been diagnosed with non-small cell lung cancer. - Patient must be able to visit the doctor's office once a week. - Patient must have adequate blood, liver, lungs and kidney function within the requirements of this study. - Female patients of child-bearing potential must test negative for pregnancy at the time of enrollment based on a serum pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 3 months following the last dose of study drug. Exclusion Criteria: Patients cannot participate in this study for any of the following reasons: - Patient has previously had chemotherapy. - Patient has previously had thoracic radiation therapy. - Patient has received treatment within the last 30 days with a drug that has not received approval by Health Canada for any indication at the time of study entry. - Female patient is pregnant or breast-feeding. - Patient is unsuitable to participate in the study in the opinion of the investigator. - Patient is unable or unwilling to take folic acid, vitamin B12 supplementation, or dexamethasone. | |
| 70 | NCT01704599 | terminated | side effect and poor clinical outcome | 0 | phase 1/phase 2 | ['psoriasis'] | ["['L40.0', 'L40.4', 'L40.8', 'L40.9', 'L40.1', 'L40.50']"] | ['humira then humira plus 3 b vitamins'] | ['NC1=NC(=O)C2=NC(CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CN=C2N1'] | Inclusion Criteria: - adults 18 or older - moderate to severe plaque psoriasis (>10% BSA) - Negative pregnancy test within 7 days before first dose of adalimumab in all women (except surgically sterile or 5 years postmenopausal) - subject must sign/date appropriate written informed consent&HIPAA authorization - Sexually active subjects of childbearing potential must agree to use medically acceptable contraception during screening and throughout the study - no evidence of active or latent tuberculosis based on a negative PPD skin test performed at screening, or within one year of starting this study. Patients with documentation of adequately treated TB may be enrolled - Patients PPD positive and CXR negative can be enrolled if they finish appropriate INH prophylaxis prior to enrollment - be willing and able to self-administer subcutaneous injections or to have a qualified person available to administer these injections - agrees to comply with protocol requirements, attend all regularly study visits and is considered to be a good study subject - meets concomitant medication washout requirements - willing to use only allowed psoriasis medications and treatments and agree not to start any topical, systemic, or phototherapy for psoriasis during the study period - adalimumab naïve Exclusion Criteria: - erythrodermic, pustular, or guttate psoriasis - skin conditions other than psoriasis that would interfere with study-related psoriasis evaluations - known sensitivity to any component of the study medications - Evidence of active infections such as fevers, chills, sweats, or history of untreated Lyme disease and active severe infections within 4 weeks before screening visit, or between the screening and Week 0 visits - history of listeriosis, untreated TB, persistent or active infections requiring hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or antifungals for purpose of treating infection, within 14 days of baseline - positive PPD and positive chest x-ray for latent or active tuberculosis - positive PPD and negative chest x-ray that have not completed appropriate INH prophylaxis - On immune compromising drug or history of immune compromising disorder or immunodeficiency - poorly controlled medical condition including, not limited to, unstable cardiovascular disease, poorly controlled diabetes, recent stroke, history of recurrent infections, or any condition for which, in the opinion of the investigators, participation in the study would place the subject at risk - hx. congestive heart failure - hx. demyelinating CNS disease - History of malignancy (other than previously treated localized carcinoma in situ of the cervix or previously treated nonmelanoma skin cancer) - history of or ongoing drug or alcohol abuse - past or present psychiatric morbidity which may compromise the study - Pregnant women, nursing mothers, or planning to become pregnant during study or within 150 days after last dose of study medication. Males planning pregnancy with spouse/partner while in study are to be excluded - plans to receive any live vaccines during study - history of liver disease - Current enrollment in another clinical study/treatment with other experimental drug or approved therapy for experimental use within 30 days prior to Week 0 - previous enrollment in this study - cannot commit to all assessments required by the protocol - disorder that compromises the subject to give written informed consent and/or comply with study procedures - considered by the investigators to be unsuitable candidate - cannot comply with the protocol washout requirements - on folic acid in doses over than the minimal daily requirements - on vitamins higher than minimal daily requirements (multivitamins are allowed) - colon polyps or cancer - prior adalimumab therapy - on screening plasma Vascular Endothelial Growth Factor level is 140 pg/ml or more |
| 71 | NCT01385657 | completed | 1 | phase 1 | ['atopic dermatitis'] | ["['L20.89', 'L20.9']"] | ['placebo', 'dupilumab'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'CCO'] | Inclusion Criteria: 1. Male or female, 18 years or older; 2. Chronic AD diagnosed by the Eichenfield revised criteria of Hannifin and Rajka that had been present for at least 3 years before the screening visit; 3. Eczema Area and Severity Index (EASI) score ≥ 12 at the screening and baseline visits; 4. Investigator's Global Assessment (IGA) score ≥ 3 at the screening and baseline visits; 5. ≥ 10% body surface area (BSA) of AD involvement at the screening and baseline visits; 6. History of inadequate response to a stable (≥ 1 month) regimen of topical corticosteroids or calcineurin inhibitors as treatment for AD within 3 months before the screening visit. Exclusion Criteria: 1. Positive Hepatitis B surface antigen, and/or positive Hepatitis C antibody at the screening visit; 2. Treatment with an investigational drug within 8 weeks or within 5 half-lives, if known, whichever is longer, before the baseline visit; 3. Treatment with leukotriene inhibitors within 4 weeks before the baseline visit; 4. Treatment with systemic corticosteroids within 4 weeks before the baseline visit; 5. Treatment with topical corticosteroids, tacrolimus, and/or pimecrolimus within 1 week before the baseline visit; 6. Systemic treatment for AD with an immunosuppressive/immunomodulating substance within 4 weeks before the baseline visit; 7. Chronic or acute infection requiring treatment with oral or IV antibiotics, antivirals, or antifungals within 4 weeks before the screening visit or superficial skin infections within 1 week before the screening visit; 8. Known history of human immunodeficiency virus (HIV) infection; 9. History of clinical parasite infection, other than treated trichomoniasis; 10. History of malignancy within 5 years before the baseline visit, with the following exceptions: participants with a history of completely treated carcinoma in-situ of cervix, and non-metastatic squamous or basal cell carcinoma of the skin were allowed; 11. Any medical or psychiatric condition which, in the opinion of the investigator or the sponsor's medical monitor, would place the participant at risk, interfere with participation in the study, or interfere with the interpretation of study results; 12. Pregnant or breast-feeding women; 13. Unwilling to use adequate birth control, if of reproductive potential and sexually active. | |
| 72 | NCT00588640 | completed | 1 | phase 1/phase 2 | ['pain', 'bladder cancer', 'breast cancer', 'cns cancer', 'colon cancer', 'esophageal cancer', 'pancreatic cancer', 'prostate cancer', 'uterine cancer', 'head and neck cancer', 'eye cancer', 'otorhinolaryngologic neoplasms'] | ["['N50.82', 'R07.2', 'R07.82', 'R10.13', 'R10.33', 'R14.1', 'R52']", "['D30.3', 'C67.5', 'C67.9', 'C79.11', 'C67.0', 'C67.1', 'D41.4']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['C18.2', 'C18.4', 'C18.6', 'C18.7', 'C18.9', 'D12.2', 'D12.3']", "['K22.2', 'K22.81', 'Q39.4', 'P78.83', 'I85.00', 'I85.01', 'I85.10']", "['C25.3']", "['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']", "['C57.4', 'D28.2']", "['C76.0', 'C47.0', 'C49.0', 'C77.0', 'D17.0', 'D21.0', 'D36.11']"] | ['d-methadone', 'd-methadone', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: Phase I and Phase II portions of the study: - 18 years of age or older - Chronic pain with average 24 hour intensity rated at least 3 on a verbal numerical scale from 0-10 during the 24 hours prior to study entry. - Give informed consent to participate in this study. - Karnofsky Performance Score (KPS) >= to 80 - Negative urine pregnancy test, verified by the study nurse, at study entry (for women of child-bearing potential). Patients must also use a medically approved contraceptive method during the study period. Phase I only: - Responsible companion living with patient during study. Phase II only: - Group 1 -- Patients must be taking chronic opioid therapy (long acting morphine, long acting oxycodone, transdermal fentanyl) at a stable dose for a minimum of four days. The dose of as needed short acting opioid does not need to be stable. - Group 2 -- Patients must not be receiving opioids and must have cancer related neuropathic pain secondary to post-chemotherapy peripheral neuropathy, post-radiation and/or post surgical plexopathy, radiculopathy or neuropathy, or post- herpetic neuralgia. Exclusion Criteria: Phase I and Phase II: - Known hypersensitivity to methadone - Patient taking methadone or with a history of methadone treatment within one month of study enrollment. - Patient that requires changes in the dose of one of the following medications within 2 weeks of study enrollment: - Abacavir, - Benzodiazepines, - Carbamazepine, - Efavirenz, - Fluconazole, - Fluvoxamine, - FOS amprenavir, - Fosphenytoin, - Naltrexone, - Nelfinavir, - Nevirapine, - Phenytoin, - Rifampin, - Rifapentine, - Risperidone, - Ritonavir, - St. John's Wort, - Zidovudine - Hepatic function tests (SGOT, alkaline phosphatase, bilirubin) greater than 2 times the upper limit of normal or creatinine greater than 1.4 within 30 days of study entry. - Neurologic or psychiatric disease sufficient, in the investigator's opinion, to compromise data collection. - Women who are pregnant or nursing. - Women of childbearing potential who do not agree to use a medically recognized method of contraception during the study period. | |
| 73 | NCT01702740 | completed | 0 | phase 1 | ['lupus erythematosus, cutaneous', 'lupus erythematosus, systemic'] | ["['M32.9', 'M32.0', 'M32.11', 'M32.12', 'M32.13', 'M32.14', 'M32.8']"] | ['1 mg/kg cnto 136', '4 mg/kg cnto 136', '10 mg/kg cnto 136', 'placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Diagnosis of cutaneous lupus erythematosus (CLE, including subacute cutaneous lupus erythematosus, discoid lupus erythematosus, or lupus erythematosus tumidus) or systemic lupus erythematosus (SLE) - Had a body weight less than or equal to 100 kg - Patients in Part A who were taking systemic medications for CLE had to be on a stable dose for 4 weeks before the first study agent infusion - Patients in Part B taking systemic medications for SLE had to be on a stable dose for at least 3 months before the first study agent infusion - Given informed consent and willing and able to adhere to the study visit schedule and other protocol requirements; agreed to avoid alcohol intake; and took adequate measures to prevent pregnancy Exclusion Criteria: - Significant history of or concurrent medical condition (other than lupus) - Use of specific previous or concurrent medications or investigational therapies - Known or suspected allergy to the study agent or it constituents, having recently donated blood, or having any significant laboratory test values requiring intervention - Patients with SLE in Part B could not have active central nervous system lupus | |
| 74 | NCT00170053 | completed | 0 | phase 1 | ['kidney diseases'] | ["['I12.9', 'N18.9', 'Q61.9', 'I12.0', 'D63.1', 'N18.1', 'N18.5']"] | ['sirolimus'] | ['CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2'] | Inclusion Criteria: 1. Primary deceased or living donor renal transplant recipients 2. Re-transplant recipients for which the first kidney transplant was lost for technical reasons with no sensitization (panel-reactive antibody [PRA] < 20%) or 1st lost due to recurrent disease, that is not steroid responsive. 3. Age > 18 4. Negative pregnancy test if female and of childbearing age. In addition, females of childbearing age must agree to use effective contraception for the duration of the study. 5. Patient must sign informed consent prior to transplant. | |
| 75 | NCT00985907 | terminated | low accrual | 0 | phase 1/phase 2 | ['multiple myeloma', 'patient participation'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['doxil, melphalan, bortezomib'] | ['N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O'] | Inclusion Criteria: Disease Characteristics: 1. Patient previously diagnosed with multiple myeloma; Durie-Salmon Stage I, II, or III based on standard criteria 2. Progressive disease. For non-secretory multiple myeloma, progressive disease is defined as bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of at least 10% over prior known level. Alternatively, development of new or worsening of existing lytic bone lesions or soft tissue plasmacytomas, or hypercalcemia (serum calcium >11.5 mg/dL), or relapse from complete response. Patient Characteristics: 1. 18 yrs or older 2. Patient has given voluntary written informed consent. 3. Unless post-menopausal or surgically sterilized, a female must be willing to use an acceptable method of birth control 4. Male patient must agree to use an acceptable method for contraception for the duration of the study. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. 6. Life expectancy is at least 3 months. 7. • Absolute Neutrophil Count (ANC) over 1,000/ul without the use of colony stimulating factors - Platelets over 50,000/ul without transfusion support 7 days - Bilirubin 2.0 mg/dl or less - aspartate aminotransferase (AST) 4 times or less upper limit normal Prior Therapy for Multiple Myeloma: Patients must have had at least 2 prior therapeutic regimens Exclusion Criteria: - Pregnant or breast feeding - History of allergic reaction to compounds containing boron or mannitol. - Active uncontrolled viral (including HIV), bacterial, or fungal infection. - Grade III or IV toxicity due to previous anti-neoplastic therapy - More than Grade 2 motor or sensory neuropathy - Myocardial infarction within 6 months of enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled arrhythmias, or electrocardiographic evidence of acute ischemia. - For any patients whose lifetime cumulative doxorubicin dose exceeds 400mg/m2, patients with left ventricular ejection fraction (LVEF) less than 35% by multigated acquisition (MUGA) . - Concurrent administration of liposomal doxorubicin, melphalan, and bortezomib (single or two drug combinations of these are permissible) - Less than 3 weeks since most recent chemotherapy or concurrent chemotherapy - Use of corticosteroids (mroe than 10 mg prednisone/day or equivalent) |
| 76 | NCT00255333 | terminated | development of this compound was discontinued. | 0 | phase 1 | ['tumors'] | ["['E88.3', 'R97.8', 'C49.A0', 'C49.A1', 'C49.A2', 'C49.A5', 'C49.A3']"] | ['inno-105'] | ['CSCC[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1)C(O)=O'] | Inclusion Criteria: 1. Have a histologically or cytologically confirmed diagnosis of a solid malignancy (patients may have either measurable or nonmeasurable disease). 2. Be ≥18 years old. 3. Not eligible for effective therapy likely to provide clinical benefit. 4. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2. 5. Acceptable pretreatment clinical laboratory results. 6. Life expectancy of greater than 12 weeks. Exclusion Criteria: 1. Have received previous treatment with INNO-105. 2. Have an active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment. 3. Are pregnant or lactating. 4. Have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up. 5. Have received any chemotherapy, immunotherapy, vaccines, monoclonal antibodies, major surgery, or irradiation, whether conventional or investigational, within 2 weeks of treatment in this study. 6. Have not recovered from acute toxicity of all previous therapy prior to enrollment. 7. Have symptomatic or untreated central nervous system (CNS) metastases. 8. Have a susceptibility to hypotension, bradycardia, and/or hypopnea, such as patients with known coronary heart disease, arrhythmias, cerebral vascular disease, and chronic obstructive airways disease (CO2-retaining). |
| 77 | NCT00073723 | completed | 1 | phase 1/phase 2 | ['non-small cell lung cancer'] | ["['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']"] | ['abi-007'] | ['[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'] | Patients must be: - Histologically or cytologically confirmed advanced stage IV NSCLC with evidence of inoperable local recurrence or metastasis - If female, non-pregnant and not lactating, with a negative serum pregnancy test, and either not of child-bearing potential or practicing an approved contraception method - Eighteen years of age or older - No other current active malignancy - Measurable disease (defined by RECIST criteria) documented radiographically - Patient must have received no prior chemotherapies for the treatment of metastatic disease. Radiation therapy to a major bone marrow-containing area must have been completed 3 or more weeks prior to study entry. Prior treatment with EGF-targeted therapies is permitted. - If, at baseline, patient has ANC greater than or equal to 1.5 x 109 cells/L; platelets greater than or equal to 100 x 109 cells/L and Hgb greater than or equal to 9 g/dL - If, at baseline, patient has AST and ALT of less than or equal to 2.5 x the upper limit of normal range; a total bilirubin NORMAL; creatinine levels less than or equal to 1.5 mg/dL and alkaline phosphatase levels less than or equal to 2.5 x the upper limit of normal range (unless alkaline phosphatase elevation is felt to be related to bone metastases and there is no radiologic evidence of hepatic metastasis) - Expected survival of greater than 12 weeks - ECOG performance status 0-1 (Karnofsky > 70) - Patient or his/her legally authorized representative or guardian has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent form prior to participation in any study-related activities. | |
| 78 | NCT00423852 | completed | 0 | phase 1/phase 2 | ['brain and central nervous system tumors', 'extragonadal germ cell tumor', 'ovarian cancer', 'teratoma', 'testicular germ cell tumor'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']", "['E29.0', 'E29.1', 'E29.8', 'E29.9', 'E89.5', 'N50.811', 'N50.812']"] | ['carboplatin', 'ifosfamide', 'paclitaxel'] | ['N[C@@H](CCCNC(N)=N)C(O)=O', 'N[C@@H](CCCNC(N)=N)C(O)=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'] | DISEASE CHARACTERISTICS: - Histologically confirmed germ cell tumor (GCT) - Primary CNS GCT allowed - Unidimensionally measurable disease OR elevated serum tumor markers (alpha-fetoprotein and/or human chorionic gonadotropin) - Advanced disease - Disease resistant to a cisplatin-based chemotherapy regimen (i.e., failed to achieve a durable complete response to cisplatin) - Known residual disease after post-chemotherapy surgery allowed PATIENT CHARACTERISTICS: - Platelet count ≥ 100,000/mm^3 - WBC ≥ 3,000/mm^3 - Creatinine clearance > 50 mL/min (unless due to tumor obstructing the ureters) - AST and ALT < 2 times upper limit of normal (ULN) - Bilirubin < 1.5 times ULN - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No active infection - Negative serology for HIV type I and II, human T-lymphotropic virus type I and II, hepatitis B or C virus, syphilis, and cytomegalovirus - Hepatitis C negative serology by RIBA or PCR - Adequate medical condition for general anesthesia PRIOR CONCURRENT THERAPY: - See Disease Characteristics - Recovered from recent surgery - At least 3 weeks since prior chemotherapy - No prior high-dose therapy with autologous bone marrow transplantation - No other concurrent chemotherapy - No other concurrent treatment (e.g., surgery or radiotherapy) | |
| 79 | NCT01314885 | completed | 1 | phase 1 | ['chronic obstructive pulmonary disease (copd)'] | ["['G91.1', 'I42.1', 'N11.1', 'J05.0', 'G47.33', 'J44.9', 'N13.8']"] | ['pf-03715455', 'ph-797804', 'placebo for pf-03715455', 'placebo for ph-797804'] | ['CC(C)(C)C1=NN(C(NC(O)=NCC2=CC=CC=C2SC2=CN3C(C=C2)=NN=C3C2=CC=CC=C2SCCO)=C1)C1=CC(Cl)=C(O)C=C1', 'CNC(=O)C1=CC=C(C)C(=C1)N1C(C)=CC(OCC2=C(F)C=C(F)C=C2)=C(Br)C1=O', '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: - Male or female (of non-child bearing potential) subjects, aged 18-50 years. - Subjects whose FEV1 and FVC at screening are both greater than or equal to 80% of their predicted value for age, race, sex and height. - Subjects who have normoresponsive airways. - Subjects who are able to successfully complete screening sputum inductions. Exclusion Criteria: - Subjects who have evidence, on review of pre-study laboratory data and full physical examination, or history of any clinically significant hematological, renal, endocrine, gastrointestinal, dermatological, hepatic, psychiatric, neurologic diseases. Specifically liver function tests and CRP must be within the reference range. - Subjects with a medical history of asthma symptomatology (ie, wheeze and/or dyspnea at rest). - Subjects who have experienced a respiratory tract infection within the previous 4 weeks or any other infection within 1 week of dosing | |
| 80 | NCT01247363 | completed | 1 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['ly2608204'] | ['O=C(NC1=NC=C(SCCN2CCCC2)S1)[C@@]1(C[C@H]1C1CCCCC1)C1=CC=C(C=C1)S(=O)(=O)C1CC1'] | Inclusion Criteria: - Patients diagnosed with Type 2 diabetes mellitus (T2DM) who are currently treated with diet/lifestyle measures alone or in combination with anti-diabetic agents, including insulins - Have fasting blood glucose (FBG) greater than or equal to 160 milligram/deciliter (mg/dL), with a subset of patients with FBG greater than or equal to 190 mg/dL in at least 2 measurements on separate days - Have a glycated haemoglobin (HbA1c) level of greater than or equal to 8% and less than or equal to 11% at screening - If female, are not of child-bearing potential due to surgical sterilisation (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause - Are males or females who are at least 18 years old (for sites outside of Singapore) or at least 21 years old (for sites within Singapore) but no more than 70 years old (for all sites) - Body mass index (BMI) greater than 18.5 kilogram/square meter (kg/m²) and less than 40.0 kg/m² - Have clinical laboratory test results within the normal range for the population or investigator site, or with abnormalities deemed clinically insignificant by the investigator - Have supine systolic blood pressure (SBP) greater than 160 millimeters of mercury (mmHg) and supine diastolic blood pressure (DBP) less than 100 mmHg - Have venous access sufficient to allow blood sampling as per the protocol - Are willing and able to comply with requirements for continuous glucose monitoring (CGM) - Are reliable and willing to make themselves available for the duration of the study and who will abide by the Clinical Research Unit (CRU) policy and procedure and study restrictions. This includes staying in-patient at the CRU for a total duration of up to 31 days - Have given written informed consent approved by Lilly and the ethical review board governing the site Exclusion Criteria: - Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or use of a drug or device other than the study drug used in this study, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study - Have significant history of past or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, metabolism or elimination of drugs or of constituting a risk when taking the study drug formulations or interfering with the interpretation of data - Have a history of a seizure disorder - A corrected QT interval greater than 450 milliseconds (msec) at screening or any personal history of ventricular tachycardia or unexplained syncope, or other abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study - Have family history of long QT syndrome or family history of sudden unexplained death - Use medications known to prolong the QT interval. - Have type 1 diabetes mellitus or a history of ketoacidosis or any other type of diabetes mellitus other than type 2 - Use of any known inducers or inhibitors of CYP3A within 14 days prior to the first dosing with study drug or intended use during the study - History of a hypoglycemic event with acute mental status alteration that was not preceded by prodromal symptoms recognizable to the patient - Fasting serum triglycerides greater than 500mg/dl - Serum creatinine greater than 1.3 mg/dL in women, greater than 1.5 mg/dL in men - Clinical evidence of active diabetic proliferative retinopathy - Known clinically significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis - Clinically significant coronary events or symptoms within 6 months prior to study entry - Clinically significant peripheral vascular disease - Have known allergies to LY2608204 or related compounds - Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies/antigen - Evidence of hepatitis B and/or positive hepatitis B surface antigen (HBsAg) - Donation or loss of blood equal to or exceeding 450 milliliter (mL) during the 3 months before the first administration of study drug - Patients who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) (1 unit equal to 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits) or patients unwilling to stop alcohol consumption 24 hours prior to admission until the completion of each in-patient study period - Patients who smoke more than 10 cigarettes or other tobacco products per day before study entry. Patients will not be allowed to smoke while in the study Unit - Have a history of drug or alcohol abuse - Intended use of over-the counter or prescription medications 7 and 14 days, respectively, prior to dosing. If this situation arises, inclusion of an otherwise suitable volunteer may be at the discretion of the investigator. Use of anti-diabetic medication [metformin, sulphonylureas, glinides, thiazolidinediones, acarbose, DPPIV inhibitors, Byetta (but not liraglutide)] by patients with type 2 diabetes mellitus is acceptable for this study - Have repeated alanine transaminase levels greater than 2.5 times the upper limit of the reference range at screening, as determined by the central laboratory - Have previously been enrolled in this clinical study or any other study of LY2608204. Exclusion Criteria for EU/UK/US Site(s) only -- - Evidence of hepatitis C and/or positive hepatitis C antibodies, at screening - Use of known drugs of abuse and/or positive findings on urinary drug screening, other than findings consistent with medication prescribed by the patient's physician or over-the-counter medications | |
| 81 | NCT01606397 | completed | 1 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['placebo', 'ly2409021'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'CC1=CC(O[C@@H](CCC(F)(F)F)C2=CC=C(C=C2)C(=O)NCCC(O)=O)=CC(C)=C1C1=CC=C(C=C1)C(C)(C)C'] | Inclusion Criteria: - Must be either a male, or a female who cannot become pregnant, who has type 2 diabetes and is either controlling diabetes through diet and exercise, or taking metformin - Have an hemoglobin A1c (HbA1c) value at screening of greater than or equal to 6.5% and less than or equal to 10.0% on a stable treatment regimen at the time of measurement - Have a screening body mass index (BMI) of 20 to 40 kg/m^2 inclusive - Have a blood pressure reading at screening of between 90 to 160 millimeters of mercury (mmHg) (systolic) and 40 to 95 mmHg (diastolic) Exclusion Criteria: - Have used insulin for diabetic control within 1 year of study entry - Have used thiazolidinediones within 3 months, or any other drugs for treatment of hyperglycemia (except metformin) within 1 month, prior to first planned dosing. Metformin is acceptable for this study. - Have clinically significant coronary artery disease - Have clinically significant peripheral vascular disease - Have clinical evidence of active diabetic proliferative retinopathy - Have known significant autonomic neuropathy as evidenced by urinary retention, orthostatic hypotension, diabetic diarrhea or gastroparesis - Impaired renal function (serum creatinine greater than 115 micromoles/liter [μmol/L] [1.3 mg/dL] in women, greater than 130 μmol/L [1.5 mg/dL] in men) - Have triglycerides greater than 4.5 millimoles per liter (mmol/L) [approximately 400 mg/dL] at screening - Were hospitalized for poor control of diabetes (keto-acidotic episode) in the last 6 months - Are allergic to LY2409021 or similar drugs - Have history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (other than diabetes), hematological, or neurological disorders capable of significantly altering the absorption, or metabolism or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data - Have used systemic glucocorticoids within 1 month prior to first dosing - Have donated 450 mL or more of blood in the last 3 months or have donated any blood within the last month - Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female), or are unwilling to stop alcohol as required by the study restrictions (1 unit = 360 mL of beer, or 150 mL of wine, or 45 mL of spirits) | |
| 82 | NCT00712790 | completed | 1 | phase 1/phase 2 | ['hepatocellular carcinoma'] | ["['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']"] | ['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: - Unresectable HCC with or without systemic metastases. - Willing, able and mentally competent to provide written informed consent prior to any testing under this study protocol, including screening tests and evaluations that are not considered to be part of the subject's routine care. - Aged 18 years or older of either gender and any race, religion or socioeconomic group. - Unequivocal diagnosis of primary HCC (as defined above) - HCC that is not amenable to surgical resection or immediate liver transplantation, or that is not optimally treatable with local ablative techniques such as radio-frequency ablation, consistent with the practice of the clinical trial centre. - Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan. - ECOG performance status 0 - 1. - Adequate haematological, renal and hepatic function as follows: - Leukocytes ≥ 2,500/μL - Absolute Neutrophil Count ≥ 1,500/μL - Platelets ≥ 50,000/μL - Haemoglobin > 9.5 g/dL - Total bilirubin ≤ 2.0 mg/dL (SIR-Spheres should not be administered as a whole liver treatment if the total bilirubin is > 2X the institutional upper limit of normal). - INR ≤ 2.0 - ALP ≤ 5 x institutional upper limit of normal - AST / ALT ≤ 5 x institutional upper limit of normal - Albumin ≥ 2.5 g/dL - Creatinine ≤ 2.0 mg/dL - The blood results must be less than 29 days old at the time of confirming patient eligibility to receive protocol treatment. - Life expectancy of at least 3 months without any active treatment. This is defined as a patient who has OKUDA I or II inoperable HCC. - Suitable for protocol treatment as determined by clinical assessment undertaken by the Investigator. - Female patients must be either postmenopausal or, if premenopausal, must have a negative pregnancy test and agree to use two forms of contraception if sexually active during their study participation. - Male patients must be surgically sterile, or if sexually active and having a pre-menopausal female partner then must be using an acceptable form of contraception. - Hepatic arterial anatomy suitable for implantation of SIR-Spheres, as assessed by hepatic angiogram. - Lung shunt fraction less than or equal to 20% as assessed by a Tc-99m macroaggregated albumin liver to lung breakthrough scan. Exclusion Criteria: - Had previous external beam radiation therapy to the liver. - Any ascites or other clinical signs of liver failure, on physical examination. - Abnormal synthetic and excretory liver function tests (LFTs) as determined by serum albumin (must be < 2.5 g/dL) and total bilirubin (must be > 2.0 mg/dL), respectively. - Tumours amenable to surgical resection for cure at presentation. - Greater than 20% lung shunting of the hepatic artery blood flow determined by Tc-99 MAA scan. - Pre-assessment angiogram and Tc-99 MAA scan that demonstrates significant and uncorrectable activity in the stomach, pancreas or bowel. - Been treated with Capecitabine within the previous 8 weeks, or who will be treated with Capecitabine within 8 weeks of treatment with SIR-Spheres, due to the possible risk of potentiating or causing liver dysfunction. - Complete main portal vein thrombosis. - Subjects who have had hepatic artery directed therapy. - Subjects who have had prior chemotherapy or other medical agents used to treat hepatocellular carcinoma. - Prior external hepatic radiation therapy for HCC, or any other concomitant therapy for HCC or any investigational agent planned while on this protocol. - Subjects with inferior vena cava (IVC) tumour thrombus or invasion - Currently receiving any other investigational agents for the treatment of their cancer. - Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least five years. - Presence of clinical signs of CNS metastases due to their poor prognosis and because progressive neurologic dysfunction would confound the evaluation of neurologic and other adverse events. - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Any of the following contraindications to angiography and selective visceral catheterization: - Bleeding diathesis, not correctable by the standard forms of therapy. - Severe peripheral vascular disease that would preclude arterial catheterization. - Portal hypertension with hepatofugal flow as documented on baseline spiral CT scan. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to SIR-Spheres. - Inability or unwillingness to understand or sign a written informed consent document (non English-speaking patients may use an interpreter). - Female subjects who are pregnant or currently breastfeeding. - For female subjects, unless postmenopausal or surgically sterile, unwillingness to practice effective contraception, as defined by the Investigator, during the study. The rhythm method is not to be used as the sole method of contraception. - For male subjects, unwillingness to practice effective contraception (as defined by the Investigator) while taking part in this study, because the effect of the SIR-Spheres treatment on sperm or upon the development of an unborn child are unknown. - Current enrolment in any other investigational drug or device study. | |
| 83 | NCT00647972 | terminated | during period 1 due to numerous orthostatic aes that occurred. subsequently, rld was reduced to 5 mg due to safety concerns. | 0 | phase 1 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['olanzapine tablets 20 mg', 'zyprexa® tablets 20 mg'] | ['CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2', 'CN1CCN(CC1)C1=NC2=CC=CC=C2NC2=C1C=C(C)S2'] | Inclusion Criteria: - healthy, adult subjects, 18 years and older - able to swallow medication Exclusion Criteria: - institutionalized subjects - history of any significant disease - use of any prescription or OTC medications within 14 days of start of study - received any investigational products within 30 days prior to start of study |
| 84 | NCT01176851 | completed | 1 | phase 1 | ['healthy'] | ["['Z76.3', 'Z76.2']"] | ['glycopyrrolate', 'glycopyrrolate', 'glycopyrrolate'] | ['C[N+]1(C)CCC(C1)OC(=O)C(O)(C1CCCC1)C1=CC=CC=C1', 'C[N+]1(C)CCC(C1)OC(=O)C(O)(C1CCCC1)C1=CC=CC=C1', 'C[N+]1(C)CCC(C1)OC(=O)C(O)(C1CCCC1)C1=CC=CC=C1'] | Inclusion Criteria: 1. Males and females healthy volunteers aged 18-65 years; 2. Written informed consent obtained before the first trial related activity. 3. Able to understand the study procedures, the risks involved and ability to be trained to use the devices correctly. 4. Body Mass Index (BMI) between 18.0 and 32.0 kg/m2; 5. Non- or ex-smokers who smoked < 5 pack years; 6. Good physical and mental status; 7. Normal blood pressure and heart rate; 8. Electrocardiogram (ECG)considered as normal; 9. Results of laboratory tests within the normal ranges. 10. Lung function measurements within the normal ranges. Exclusion Criteria: 1. Blood donation (equal or more than 450 ml) or blood loss less than 8 weeks before inhalation of the study medication; 2. Pregnant or lactating women or women of childbearing potential, UNLESS they are using one or more of the acceptable methods of contraception. Male subjects not willing to use an acceptable method of contraception. 3. Positive HIV1 or HIV2 serology; 4. Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C; 5. Unsuitable veins for repeated venipuncture; 6. History of substance abuse or drug abuse within 12 months prior to screening visit or with a positive urine drug screen at screening; 7. Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation; 8. Clinically significant and uncontrolled cardiac, hepatic, renal, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol; 9. Participation in another clinical trial less than 8 weeks prior to inhalation of the study medication; participation in another clinical trial using radioactive material within 1 calendar year; 10. History of hypersensitivity to M3 Antagonists or any of the excipients contained in any of the formulations used in the trial; 11. Any drug treatment, including prescribed or OTC medicines as well as vitamins, homeopathic remedies etc, taken in the 14 days (2 months for enzyme-inducing or enzyme-inhibiting drugs e.g., glucocorticoids, phenobarbital, isoniazid) preceding the first intake of the study drug, with the exception of occasional paracetamol (maximum 2 g per day with a maximum of 10 g per 14 days for mild non-excluding conditions). 12. Treatment within the previous 3 months with any drug known to have a well defined potential for hepatotoxicity (e.g. isoniazide, nimesulide, ketoconazole). 13. Subjects who refuse to abstain from alcohol or caffeine containing foods or beverages or grapefruit containing foods or beverages from 48 hour prior to the first intake of study medication and for the entire duration of the study. 14. Heavy caffeine drinker. | |
| 85 | NCT03070730 | terminated | recruitment was slow and subjects declined participation after signing the icf. | 0 | phase 1/phase 2 | ['postural orthostatic tachycardia syndrome', 'orthostatic intolerance'] | ["['I95.1', 'R80.2', 'R51.0']"] | ['droxidopa', 'atenolol', 'placebos'] | ['N[C@@H]([C@H](O)C1=CC(O)=C(O)C=C1)C(O)=O', 'CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1', 'COCCC1=CC=C(OCC(O)CNC(C)C)C=C1'] | Inclusion Criteria: - CDC criteria for chronic fatigue syndrome - Evidence of postural tachycardia syndrome with symptoms of orthostatic intolerance Exclusion Criteria: - Pregnant or lactating females. The administration of droxidopa is harmful to the fetus - Concomitant therapy with anticholinergic, alpha-, and beta-adrenergic antagonists or other medications that affect autonomic function - Clinically significant coronary artery, cerebrovascular or peripheral vascular disease - Cardiac arrhythmias - Systemic illness that might affect autonomic function such as congestive heart failure, hypertension, renal, pulmonary, and hepatic disease, anemia, malignancies, thyroid disease, and alcoholism - Severe depression, severe anxiety disorder (score of on the Beck Depression Inventory > 29 or score on the Beck Anxiety Inventory of ≥ 36) or psychosis - Antidepressant treatment by MAO inhibitors within 2 weeks before the study - Glaucoma - Liver disease - Subjects with a history of reaction to local anesthetic will be excluded from the study - Subjects who have a history of any bleeding disorders or significantly impaired wound healing will be excluded. Subjects who are using any medications such as Coumadin or Plavix will be also excluded - Subjects who are currently enrolled in any other studies using investigational products |
| 86 | NCT00426829 | terminated | low accural | 0 | phase 1 | ['liver cancer', 'hepatocellular carcinoma', 'cholangiocarcinoma'] | ["['D13.4', 'Z85.05', 'C22.8', 'C78.7', 'C22.9', 'D37.6']", "['C22.0', 'C4A.9', 'C7B.1', 'C4A.0', 'C4A.31', 'C4A.51', 'C4A.8']", "['C22.0', 'C22.1', 'C4A.9', 'C7B.1', 'D09.9', 'C4A.0', 'C4A.31']"] | ['bevacizumab'] | ['[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1'] | Inclusion Criteria: - Cytologic or histologic proof of primary liver cancer (hepatocellular carcinoma or cholangiocarcinoma). Patients with non-metastatic, unresectable disease are eligible. Patients with positive margins after surgical resection are eligible. Metastasis is defined as unequivocal evidence of extrahepatic disease based on CT imaging, excluding nodal disease. - Tumors must not be greater than 10cm (small satellite lesions around a larger lesion are allowed), all of which can be encompassed in a radiation treatment field (as assessed by the radiation oncologist). - Prior chemotherapy, transarterial chemoembolization and radiofrequency ablation are permitted. A minimum of four weeks must have elapsed between prior treatment and planned protocol therapy. - Prior liver resection is permitted as long as the interval between surgery and enrollment is at least 4 weeks. - Karnofsky performance status >/= 70 are eligible. - There is no age restriction. - Absolute granulocyte count >/= 1,500 cells/mm3, hemoglobin >/= 8 gm/dL and platelet count >/= 80,000 cells/mm3. - Serum creatinine </= 1.5 mg/dl. - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 3 times the upper limit of normal. Serum bilirubin </= 5mg/dL prior to the start of therapy. - A signed study-specific consent form, which is attached to this protocol. Exclusion Criteria: - Child-Pugh class C cirrhosis. - Gross ascites seen on CT that precludes accurate targeting of the tumor with radiation therapy - Proteinuria at screening as demonstrated by either Urine protein:creatinine (UPC) ratio > 1.0 at screening OR Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate < 1g of protein in 24 hours to be eligible). - Patients currently receiving anticoagulation treatment with coumadin, low molecular weight heparin or IV heparin. Evidence of bleeding diathesis or coagulopathy. Anticoagulation for line maintenance is permitted. - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0. - Serious, nonhealing wound, ulcer, or bone fracture. - Clinically significant cardiac disease (e.g., uncontrolled hypertension [blood pressure of >150/100 mmHg on medication], history of myocardial infarction within 6 months, unstable angina), New York Heart Association (NYHA) Class II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or Class II or greater peripheral vascular disease. - History of aneurysms, strokes, transient ischemic attacks, and arteriovenous malformations within 6 months. - Prior unanticipated severe reaction to bevacizumab. - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0 - Patients who have had an organ allograft. - Pregnant women are excluded from this study; women of childbearing potential must agree to practice adequate contraception (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) and to refrain from breast feeding, as specified in the informed consent. Women of child-bearing potential are defined as those women who have not had surgical sterilization or been menopausal for 12 consecutive months. - Male patients must agree not to father a child and must agree to use a condom. - Prior radiation therapy to an upper abdominal or lower thoracic field that could overlap with the proposed treatment field. - Serious concomitant medical or psychiatric disorders that place the patient at high risk for non-compliance with or morbidity due to protocol therapy. - Patients with a history of hypertension must be well-controlled (</= 140/90 mmHg on a stable regimen of antihypertensive therapy) |
| 87 | NCT01555008 | completed | 1 | phase 1 | ['type 2 diabetes mellitus', 'renal impairment'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']", "['M10.38', 'M10.30', 'M10.311', 'M10.312', 'M10.319', 'M10.321', 'M10.322']"] | ['lx4211', 'lx4211 placebo'] | ['CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Adults ≥18 to ≤80 years of age - History of T2DM for at least 6 months prior to screening - Moderate to severe renal impairment and not actively on dialysis - Willing and able to perform self-monitoring of blood glucose - Willing and able to provide written informed consent Exclusion Criteria: - History of type 1 diabetes mellitus, diabetic ketoacidosis (within the previous 6 months), or diabetes resulting from pancreatic disorder or secondary diabetes (from acromegaly and/or Cushing's disease) - Subjects who have received a renal allograft - Subjects expecting to require dialysis or to undergo kidney transplantation within 3 months of study dosing - Presence of active hepatic disease or clinically significant abnormal liver function tests at Screening or planned study Day -1 - Subjects with a history of heart attack, severe/unstable angina, or coronary revascularization procedure within 6 months prior to study Day -2 - History of clinically significant cardiac arrhythmias within 1 year prior to study Day -2 - Subjects with congestive heart failure - Subjects with uncontrolled Stage III hypertension - History of 2 or more emergency room visits, doctors' visits, or hospitalizations due to hypoglycemia within the 6 months prior to planned study Day -2 - History of alcohol or illicit drug abuse within 1 year prior to Screening - History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C - Major surgery within 6 months prior to planned study Day -2 - History of any malignancy within the last 5 years - Triglycerides >1000 mg/dL at Screening or planned study Day -1 - History of any serious adverse reaction or hypersensitivity to an SGLT inhibitor - Use of corticosteroids within 2 weeks prior to study Day 1 - Use of any investigational drug within 30 days prior to study Day 1, or investigational protein or antibodies within 60 days of Day 1 - Positive urine pregnancy test at Screening - Positive urine screen for illicit drug abuse at Screening - Prior exposure to LX4211 | |
| 88 | NCT01469065 | completed | 1 | phase 1 | ['diabetes mellitus, type 2'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['pf-04991532', 'pf-04991532', 'pf-04991532', 'pf-0499132', 'placebo'] | ['[H][C@@](CC1CCCC1)(N1C=NC(=C1)C(F)(F)F)C(O)=NC1=NC=C(C=C1)C(O)=O', '[H][C@@](CC1CCCC1)(N1C=NC(=C1)C(F)(F)F)C(O)=NC1=NC=C(C=C1)C(O)=O', '[H][C@@](CC1CCCC1)(N1C=NC(=C1)C(F)(F)F)C(O)=NC1=NC=C(C=C1)C(O)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Patients with type 2 diabetes mellitus who are taking either no medication for the treatment of diabetes (diet/exercise therapy only), or who are taking only a single oral anti-diabetic drug (OAD) that can be temporarily discontinued for approximately 8-10 weeks. For those taking a single OAD, treatment should be stable, where this is defined as no change in the treatment, including dose, over the past 3 months prior to Screening. OAD medications that are acceptable to be discontinued include: a sulfonylurea (SU), a meglitinide, a biguanide (eg, metformin), a dipeptidyl peptidase 4 inhibitor (DPP-4i), or an alpha glucosidase inhibitor. - Body Mass Index (BMI) of 18.5 to 45.0 kg/m2; and a total body weight >50 kg (110 lbs). - HbA1c >/=7% and </=10% if the patient is on diet/exercise therapy only and does not require any OAD discontinuation. HbA1c >/=6.5% and </=9% if the patient requires to be washed off an OAD. Exclusion Criteria: - Evidence or history of diabetic complications with significant end organ damage. - History of stroke or transient ischemic attack. - History of myocardial infarction. - History of coronary artery bypass graft or stent implantation. - Clinically significant peripheral vascular disease. - Any history or clinical evidence of congestive heart failure, NYHA Classes II IV. - Current history of angina/unstable angina. - One or more episodes of hypoglycemia within the last 3 months, or two or more episodes of hypoglycemia within the last 6 months. - A positive urine drug screen. - Use of tobacco or nicotine-containing products in excess of the equivalent of 10 cigarettes per day. - Blood pressure >/=160 mm Hg (systolic) or >/=100 mm Hg (diastolic), following at least 5 minutes of rest. - Pregnant or nursing females; females of childbearing potential. | |
| 89 | NCT01217411 | terminated | slow accrual coupled with discontinuation of study drug. | 0 | phase 1 | ['estrogen receptor-negative breast cancer', 'extensive stage small cell lung cancer', 'her2-negative breast cancer', 'her2-positive breast cancer', 'male breast cancer', 'recurrent breast cancer', 'recurrent melanoma', 'recurrent non-small cell lung cancer', 'recurrent small cell lung cancer', 'stage iv breast cancer', 'stage iv melanoma', 'stage iv non-small cell lung cancer', 'tumors metastatic to brain', 'unspecified adult solid tumor, protocol specific'] | ["['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C50.021', 'C50.022', 'C50.029', 'C50.121', 'C50.122', 'C50.129', 'C50.621']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['G47.13', 'J01.41', 'K11.22', 'K12.0', 'N96', 'F33.8', 'G03.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['C79.81', 'D24.1', 'D24.2', 'D24.9', 'D49.3', 'C44.501', 'D48.60']", "['C43.0', 'C43.31', 'D03.9', 'C43.51', 'C43.9', 'D03.0', 'C43.4']", "['C78.00', 'C78.01', 'C78.02', 'D14.30', 'D14.31', 'D14.32', 'C34.2']", "['H01.009', 'H02.209', 'H02.009', 'H02.109', 'H04.209', 'H05.409', 'H10.509']"] | ['gamma-secretase/notch signalling pathway inhibitor ro4929097'] | ['CC(C)(C(=O)NCC(F)(F)C(F)(F)F)C(=O)N[C@H]1C2=CC=CC=C2C2=CC=CC=C2NC1=O'] | Inclusion Criteria: - Patients who have histologically or cytologically confirmed breast cancer or other cancers (such as lung cancer, melanoma, etc) with newly diagnosed metastatic disease to the brain will be eligible for the Phase 1 study only, however, those patients who have available systemic therapeutic options with a demonstrated survival benefit will not be eligible; for Phase 2, patients must have histologically or cytologically confirmed estrogen receptor negative breast cancer with newly diagnosed metastatic disease to the brain - Patients must have measurable disease in the brain, defined as at least one lesion that can be accurately measured in at least two dimensions (longest diameter and its longest perpendicular diameter to be recorded) - There is no limit on type or number of prior therapies, except that prior therapy with notch inhibitors is not allowed, and patients should not have received prior cranial radiation; therapy naïve patients are eligible; at least 14 days (2 weeks) must have elapsed from any prior experimental therapy, chemotherapy or radiotherapy; toxicities from prior chemotherapy or radiotherapy should have resolved to < grade 2; patients with newly diagnosed brain metastases who have received therapeutic regimens with well-characterized, delayed toxicity (e.g. hematologic toxicity observed following carmustine [BCNU] or mitomycin C) will not receive experimental therapy until the patient has adequately recovered from all drug related toxicities - Karnofsky performance status (KPS) >= 70%; Recursive Partitioning Analysis (RPA) class I or II; a small feasibility cohort of 10 RPA class III (KPS < 70%) patients may be enrolled, however these patients, if enrolled will not be included in the efficacy analysis - Hemoglobin >= 9g/dL - Absolute neutrophil count >= 1,000/mcL - Platelets >= 100,000/mcL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal - Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limits of normal - Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal - Tumor HER2/neu status may be positive or negative - Women of childbearing potential and men must use two forms of contraception (i.e., barrier contraception and one other method of contraception) for the duration of study participation, and for at least 12 months post-treatment; should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately; prior to dispensing RO4929097, the investigator must confirm and document the patient's agreement to the use of two contraceptive methods, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of RO4929097 - Ability to understand and the willingness to sign a written informed consent document - A tumor site (outside the central nervous system) for needle biopsy for research purposes is preferable - Ability to swallow pills Exclusion Criteria: - At least 14 days (2 weeks) must have elapsed from any prior experimental therapy, chemotherapy or radiotherapy; toxicities from prior chemotherapy or radiotherapy should have resolved to < grade 2 - Patients may not be receiving any other investigational agents - Patients with leptomeningeal metastases should be excluded from this clinical trial - History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 - Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible - Patients taking medications that are generally accepted by the QTdrugs.org Advisory Board to carry a risk of torsades de pointes, including antiemetics, are ineligible - Preclinical studies indicate that RO4929097 is a substrate of CYP450 family 3, subfamily A, polypeptide 4 (CYP3A4) and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; if such patients cannot be switched to alternative medications, they will be ineligible to participate in this study - Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow tablets - Patients who are known to be serologically positive for hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible - Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study - Uncontrolled electrolyte abnormalities including hypocalcemia, hypomagnesemia, and hypokalemia; uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, a history of torsades de pointes or other significant cardiac arrhythmias, stable atrial fibrillation, or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with RO4929097 - Cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) - Patients who have not recovered to < Common Terminology Criteria for Adverse Events (CTCAE) grade 2 toxicities related to prior therapy are not eligible to participate in this study - A requirement for antiarrhythmics or other medications known to prolong QTc |
| 90 | NCT01431898 | completed | 1 | phase 1 | ['hepatitis c'] | ["['B18.2', 'B17.10', 'B17.11', 'B19.20', 'B19.21', 'B15.0', 'B15.9']"] | ['gs-9669 tablets', 'placebo to match gs-9669 tablet'] | ['CC1=CC[C@@H](CC1)C(=O)N([C@H]1CC[C@](O)(CO[C@H]2CCOC2)CC1)C1=C(SC(=C1)C#CC(C)(C)C)C(O)=O', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Adult subjects 18-65 years of old, inclusive - Documented chronic HCV infection to be of at least 6 months duration and plasma HCV RNA ≥ 5 log10 IU/mL at screening. - HCV treatment naïve or PEG-IFN, IFN, and/or RBV experienced (treatment must have ceased at least 3 months prior to screening). Treatment experienced subjects should not exceed 40% of the subjects enrolled in each cohort - Mono-infection with HCV genotype 1a for Cohorts 1, 2, 3, 4, and 5 and mono-infection with HCV genotype 1b for Cohort 6 and 7. - Estimated creatinine clearance ≥ 70 mL/min, - QTcF interval ≤ 450 msec for males and ≤ 470 msec for females, QRS duration < 120 msec, PR interval < 220 msec, - Body mass index (BMI) of 19.0 to 34.0 kg/m^2, inclusive. Exclusion Criteria: - Urine drug screen positive for illicit/illegal drugs - ALT and AST levels > 5 times the upper limit of the normal range (ULN) - Direct bilirubin > ULN, clinical or other laboratory evidence of hepatic decompensation (i.e., platelets < 90,000/mm^3, prothrombin time ≥ 1.5 × ULN and albumin < 3.5 g/dL) are not eligible for study participation. - Subjects with an absolute neutrophil count (ANC) < 1,000 cells/mm^3 (< 750 cells/mm^3 for black or African-American subjects), hemoglobin (Hb) < 11 g/dL, - Coinfected with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or another HCV genotype other than genotype 1a/b are not eligible for study participation. - Evidence of hepatocellular carcinoma (e.g., a-fetoprotein > 50 ng/mL or as indicated by recent ultrasound or other standard of care measure) - History of significant cardiac disease. The following ECG abnormalities at screening are exclusionary: QTcF (QT corrected using Fridericia's formula=QT/RR^0.333) > 450 msec for males and > 470 for females; QRS > 120 msec (left or right hemiblock is not exclusionary); PR interval > 220 msec; bradycardia (< 45 beats per minute); second or third degree heart block. - History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol - History of a primary gastrointestinal disorder that could interfere with the absorption of the study drug or that could interfere with normal gastrointestinal anatomy or motility | |
| 91 | NCT01640834 | completed | 1 | phase 1 | ['diabetes mellitus, type 1'] | ["['E10.65', 'E10.9', 'E10.21', 'E10.36', 'E10.41', 'E10.42', 'E10.44']"] | ['ly2409021', 'placebo', 'glucagon'] | ['CC1=CC(O[C@@H](CCC(F)(F)F)C2=CC=C(C=C2)C(=O)NCCC(O)=O)=CC(C)=C1C1=CC=C(C=C1)C(C)(C)C', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O', 'N[C@@H](CCCNC(N)=N)C(O)=O'] | Inclusion Criteria: - Have had type 1 diabetes mellitus (T1DM) based on the World Health Organization classification for at least 1 year and have a daily insulin dose ≤1.5 international units (IU) per kilogram (kg) of body weight - Have a glycated hemoglobin A1c (HbA1c) of no greater than 9.0% as measured at screening - Have a body mass index (BMI) ≥19.0 and ≤35.0 kilograms per meter squared (kg/m^2) - Have given written informed consent approved by Lilly Exclusion Criteria: - Received any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 3 months prior to screening - Have had more than 1 episode of severe hypoglycemia within 3 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness - Are pregnant or intend to become pregnant during the course of the study - Women who are breastfeeding - Have a history of stroke, myocardial infarction, heart failure, unstable angina, or a coronary revascularization procedure within 6 months of screening - Have fasting triglycerides >500 milligrams per deciliter (mg/dL) (5.65 millimoles per liter [mmol/L]) - Have obvious clinical signs, symptoms, or laboratory evidence of liver disease (alanine transaminase [ALT] or aspartate transaminase [AST] greater than 2 times the upper limit of normal at screening) - Have a history of renal transplantation or are currently receiving renal dialysis or have a screening creatinine >2.0 mg/dL (177 micromoles per liter [μmol/L]) - Have had any other disease, illness, or condition (including known diabetic autonomic neuropathy, drug or alcohol abuse, or psychiatric disorder) within the 6 months prior to screening that precludes the participant from following and completing the study or could increase their risk for hypoglycemia, according to the investigator's judgment - Are currently enrolled in, have completed, or have discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study | |
| 92 | NCT00254293 | completed | 1 | phase 1/phase 2 | ['rheumatoid arthritis'] | ["['M06.9', 'M05.9', 'M06.08', 'M06.00', 'M06.011', 'M06.012', 'M06.019']"] | ['abatacept or placebo (both as iv & sc solution)', 'abatacept or placebo (both as iv & sc solution)', 'abatacept or placebo (both as iv & sc solution)', 'abatacept or placebo (both as iv & sc solution)', 'abatacept or placebo (both as iv & sc solution)', 'abatacept'] | ['[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O', '[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O', '[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O', '[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O', '[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O', '[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)[C@@]4([H])C3)O[C@@]21O'] | Inclusion Criteria: - Meet ARA criteria for diagnosis of RA with active disease. - RA diagnosis for at least 1 year. - > = 6 swollen joints. - > = 8 tender joints. - Taking methotrexate (MTX) or MTX plus not more than 1 added oral DMARD for > = 3 months and stable for 28 days prior to dosing. Exclusion Criteria: - Serious acute or bacterial infection in last 3 months. - Chronic or recurrent bacterial infections. - History of TB within previous 3 years or old TB not adequately treated. - Specific lab test abnormalities - History of cancer within 5 years. - Exposure to CTLA4Ig (Cytotoxic T-lymphocyte (T-cell)-associated antigen 4Ig), belatacept, rituximab, efalizumab, alefacept, or other investigational drug or biologic. - Treatment with hydroxychloroquine, azathioprine, leflunomide, immunoadsorption columns, mycophenolate mofetil, cyclosporine, D-Penicillamine or calcineurin inhibitors. - Exposure to live vaccines. | |
| 93 | NCT00369226 | completed | 1 | phase 1/phase 2 | ['hematologic malignancies'] | ["['E70.338', 'E70.339', 'P09.3', 'O28.0', 'P61.8', 'P61.9', 'T45.8X1A']"] | ['bortezomib (velcade)', 'tacrolimus', 'methotrexate'] | ['CC(C)C[C@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C1=CN=CC=N1)B(O)O', 'COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O', 'CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O'] | Inclusion Criteria: - Patients with hematologic malignancies including myelodysplastic syndrome (MDS), who are at a high risk of complications after myeloablative transplantation - Patients have a donor (both related and unrelated) who are mismatched according to protocol criteria - 18 years of age or older - Performance status 0-2 - Life expectancy of > 100 days - Female subject is either post-menopausal or sterilized or willing to use an acceptable form of birth control - Male subject agrees to use an acceptable form of birth control Exclusion Criteria: - Evidence of HIV infection - Total bilirubin > 2.0mg/dl that is due to hepatocellular dysfunction - Aspartate aminotransferase (AST) > 90 - Known active hepatitis B or C - Serum creatinine > 2.0 - Greater than or equal to Grade 2 peripheral neuropathy within 21 days of enrollment - Prior allogeneic stem cell transplant - Patients with myeloproliferative disease (e.g. myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia) - Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities - Hypersensitivity to Velcade, boron or mannitol - Pregnant or breast feeding - Patient has received other investigational drugs 14 days before enrollment - Serious medical or psychiatric illness - Another active solid tumor malignancy at the time of study entry | |
| 94 | NCT00649207 | completed | 1 | phase 1 | ['brain diseases', 'brain neoplasms', 'central nervous system diseases', 'neoplasm metastasis', 'nervous system neoplasms'] | ["['G46.8', 'G94']", "['C71.7', 'C71.9', 'C79.31', 'D33.0', 'D33.1', 'D33.2', 'D49.6']", "['G37.9', 'G37.3', 'G13.1', 'G09', 'G13.8', 'G37.8']", "['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['abt-888'] | ['C[C@@]1(CCCN1)C1=NC2=CC=CC(C(N)=O)=C2N1'] | Inclusion Criteria: - Age is greater than or equal to 18 years. - Histologically or cytologically confirmed non-CNS primary solid malignancy. - Pathologically or radiographically confirmed metastatic disease in the brain. Subjects with non-measurable lesions, including leptomeningeal carcinomatosis, are eligible. - WBRT is clinically indicated, with the exception of prophylactic treatment. - Karnofsky Performance Status (KPS) greater than or equal to a score of 70. - Adequate hematology, renal and hepatic function. - Both men and women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 2 months following completion of protocol therapy. - Total abstinence from sexual intercourse (minimum one complete menstrual cycle) - A vasectomized partner * Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration - Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream) - Subject is capable of understanding and complying with parameters as outlined in the protocol. - Subject or the subject's legally acceptable representative has voluntarily signed and dated the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. Exclusion Criteria: - Brain metastases secondary to germ cell tumor or lymphoma malignancy. - Primary central nervous system (CNS) neoplasm. - Prior or concurrent administration of the following therapies or treatments: - Prior treatment with WBRT - SRS performed less than 14 days prior to WBRT D1, or is scheduled to occur within 30 days of the last WBRT session - Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy was less than 14 days prior to WBRT D1. Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction - Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment. - Known seizure disorder (status epileptics) that is uncontrolled, or seizures occurring greater than or equal to 3 times a week over the past month. - If female, subject is pregnant or breast-feeding. - Clinically significant and uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder, including but not limited to: - Active uncontrolled infection - Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia - Any other illness condition(s) that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit compliance with study requirements - Unable to swallow and retain oral medications. - Known contraindication to enhanced MRI and CT, including but not limited to: - Presence of metal objects within the body such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel - History of immediate or delayed hypersensitivity reaction or other contraindication to contrast agents including but not limited to gadolinium and iodine - Previous enrollment in this study or another study involving the investigation of ABT-888, with the exception of receiving a single dose of study drug. - Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-888 and/or WBRT. | |
| 95 | NCT01464112 | completed | 1 | phase 1 | ['multiple myeloma'] | ["['C90.01', 'C90.02', 'C90.00']"] | ['jnj-2641585 / velcade / 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: - Eastern Cooperative Oncology Group (ECOG) Performance status score 0-2 - Measurable or secretory multiple myeloma - Relapse or progression of myeloma following prior systemic antineoplastic therapy - Pretreatment clinical laboratory values meeting protocol-specified criteria - Left ventricular ejection fraction rate within normal limits Exclusion Criteria: - Peripheral neuropathy or neuralgia >=2, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 - Diagnosis of primary amyloidosis, plasma cell leukemia, or other similar conditions - Diagnosis of Waldenstrom macroglobulinemia with protocol-specified immunoglobulin levels - Prior histone-deacetylase inhibitor therapy - More than 3 prior lines of therapy - Cardiac risk factors: unstable angina or myocardial infarction within the preceding 12 months, congestive heart failure (New York Heart Association Class II-IV), known presence of dilated, hypertrophic, or restrictive cardiomyopathy - Any other cardiac abnormality that, in the opinion of the investigator, medical monitor, or consultant cardiologist, may place the patient at an unacceptably increased risk with study drug - History of any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, atrial fibrillation, cardiac arrest, Mobitz II second degree heart block, or third degree heart block - QTc at Screening > 450 ms in males / > 470 ms in females - Family history of short QT syndrome, long QT syndrome - Obligate use of a cardiac pacemaker - Use of medications that may cause Torsades de Pointes | |
| 96 | NCT01373450 | completed | 1 | phase 1 | ['type 2 diabetes mellitus'] | ["['E11.65', 'E11.9', 'E11.21', 'E11.36', 'E11.41', 'E11.42', 'E11.44']"] | ['oxyntomodulin', 'liraglutide 0.6 mg', 'liraglutide 1.2 mg', 'placebo for oxyntomodulin', 'placebo for liraglutide'] | ['CN(C)C(=N)NC(N)=N', 'CN(C)C(=N)NC(N)=N', '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: - Have a body mass index (BMI) of ≤38.0 kg/m^2 - Have a clinical diagnosis of Type 2 diabetes mellitus - Have a glycated hemoglobin (HbA1C) at screening ≤9.0%; fasting plasma glucose should not exceed 300 mg/dL (16.8 mmol/L) - Judged to be in good health Exclusion Criteria: - Have a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study - Have a history of stroke, chronic seizures, major neurological disorder, clinically significant endocrine, cardiovascular, hematological, hepatic, renal, respiratory, or genitourinary abnormalities or diseases - Have untreated hypertension with blood pressure of >160/95 mmHg - Have a history of neoplastic disease within the past 5 years - Have a history of hypersensitivity to OXM, liraglutide, insulin or Haemaccel® - Unable or unwilling to comply with restrictions around concomitant medications - Consume excessive amounts of alcohol, coffee, tea, cola, or other caffeinated beverages daily - Have had major surgery, donated or lost 1 unit of blood (approximately 500 mL) or participated in another investigational study within 4 weeks - Have a history of significant multiple and/or severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food - Currently a regular user (including use of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months - Are unwilling or unable to consume the standardized meals during the study and/or is on a carbohydrate restricted diet (i.e., a diet <100 grams per day of carbohydrate) | |
| 97 | NCT00314782 | completed | 1 | phase 1 | ['prostate cancer'] | ["['C61', 'D29.1', 'D40.0', 'Z15.03', 'Z80.42', 'Z85.46', 'Z12.5']"] | ['zd4054 (zibotentan)', 'docetaxel', 'placebo'] | ['COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=C1)C1=NN=CO1', '[H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1', 'CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O'] | Inclusion Criteria: - Provision of informed consent - Histological or cytological confirmation of prostate cancer - Evidence of metastatic disease on CT scan, MRI, or bone scan - Surgically or continuously medically castrated with LHRH analogue - Progressive disease after most recent therapy - Disease progression by CT/MRI - Bone scan progression: appearance of 1 or more new lesions since last bone scan - Rising PSA - World health organization (WHO) performance status 0 to 2 - Life expectancy of 12 weeks or longer Exclusion Criteria: - Use of anti-hormonal therapies (including ketoconazole, aminoglutethimide, finasteride and anti-androgen therapies) within 4 weeks of starting study treatment, except for bicalutamide and nilutamide which are excluded within 6 weeks of starting study treatment. Estramustine or estrogens, if taken, have to be stopped at least 4 weeks before starting treatment. - Definite or suspected personal history or family history of adverse drug reactions, or hypersensitivity to drugs that are endothelin antagonist; history of severe hypersensitivity reactions to drugs formulated with polysorbate 80. - Prior cytotoxic chemotherapy for metastatic prostate cancer - Radiotherapy within 4 weeks before the start of study therapy - Systemic radionuclide therapy (ie strontium chloride Sr89, 186Re-labeled HEDP, or 153Sm-EDTMP pentasodium) within 12 weeks before entering study - Use of potent CYP450 inhibitors (such as itraconazole, ritonavir, indinavir, erythromycin, troleandomycin, clarithromycin, diltiazem, verapamil) within 2 weeks before study entry. - Use of potent CYP450 inducers (such as phenytoin, rifampicin, carbamazepine and phenobarbitone, St. John's Wort) within 2 weeks before study entry. NOTE: Dexamethasone is a known inducer of CYP2D6 and CYP3A4 but is not considered exclusionary for purposes of this study. - New neurologic symptoms or signs consistent with acute or evolving spinal cord compression confirmed by magnetic resonance imaging (MRI) (except for those previously treated and have stable symptoms). - History of past or current epilepsy, epilepsy syndrome, or other seizure disorder - History of Migraine or chronic headache - Symptomatic central nervous system (CNS) metastases - Absolute Neutrophil Count (ANC) <1.5 x 109/L (1,5000/mm3) - Platelet count < 100 x 109/L (100,000/mm3) - Serum bilirubin greater than the upper limit of normal (ULN) - Alanine amino transferase (ALT) or aspartate amino transferase (AST) greater than 1.5 times the upper limit of normal (ULN) - Creatinine clearance <50 mL/min - QT interval corrected for heart rate by the Barrett Formula (QTc) > 470 msec at screening - New York Heart Association (NYHA) class II-IV Heart Disease - Myocardial infarction (heart attack) within past 3 months - CTCAE grade ≥2 Peripheral Neuropathy - Treatment with a non-approved or investigational drug within 30 days before study entry - Evidence of any other significant clinical symptoms, abnormal laboratory findings or recent surgery that patients has not recovered from that make it undesirable for the patient to participate in the study in the opinion of the investigator(s) - Involvement in the planning and conduct of the study - Previous treatment in the present study | |
| 98 | NCT00209612 | withdrawn | due to strong side effect | 0 | phase 1/phase 2 | ['gastric cancer'] | ["['C05.2', 'C10.0', 'C16.0', 'C16.4', 'C17.0', 'C17.1', 'C17.2']"] | ['taxol', 'campt, topotesin'] | ['[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', 'CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=CC=C(OC(=O)N3CCC(CC3)N3CCCCC3)C=C12'] | Inclusion Criteria: - Histologically confirmed metastatic or recurrent gastric cancer with prior treatment for advanced disease. - Patients who have received 1cycle cancer therapy (radiotherapy, chemotherapy or chemoradiotherapy) given > 4 weeks prior to the beginning of study therapy - At least one measurable lesion according to the RECIST criteria. Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques(Except for Phase I setting). - Patients aged between 20 and 75 years, inclusive, at the time of acquisition of informed consent - Patients with performance status(ECOG) 0 to 2 - Abnormal hematologic values (WBC ≥ 3.5 x 109/L, Hemoglobin ≥ 9.0g/dl, platelet count ≥ 100 x 109/L) - Serum cleatinine ≤ 1.5mg/dl - Serum bilirubin ≤ 1.5mg/dl. ALT, AST ≤ 2.0 x upper normal limit (or ≤ 3 x upper normal limit in the case of liver metastases) - Normal ECG - Life expectancy ≥ 3 months - Patients who have given written informed consent to participate in this study Exclusion Criteria: - Patients with active multiple cancers; or even if the multiple cancers are metachronous, have a disease-free period of less than 5 years (but excluding cancer in situ and skin cancer) (Except for Phase I setting) - Serious, uncontrolled, concurrent infection(s) or illness(es) - Patients with no serious concurrent complications (such as heart disease, Intestinal pneumonia) - Patients with Liver cirrhosis - Patients with fresh hemorrhage from the gastrointestinal tract - Patients with poorly controlled diabetes or are treated by continuous use of insulin - Patients with concurrent psychiatric disease or psychotic symptoms, and judged to have difficulties participating in the study - Patients with retention of body fluid(pleural effusion, ascites, pericardial effusion) necessitating treatment - Patients with diarrhea (watery stool) - Patients with infection, intestinal palsy or intestinal occlusion - Patients with brain metastasis - Patients with Gilbert syndrome - Patients who have experienced serious drug allergy in the past - Patients who are pregnant and lactating or hope to become pregnant during the study period - Patients with prior Taxan (Paclitaxel, Docetaxel) or CPT-11 treatment - Patients with neuropathy ≥ grade 2 - Others, patients judged by the investigator or subinvestigator to be inappropriate as subject |
| 99 | NCT01078376 | terminated | business decision (see below) | 0 | phase 1 | ['hypertension'] | ["['I15.0', 'I97.3', 'K76.6', 'P29.2', 'G93.2', 'H40.053', 'I10']"] | ['azilsartan medoxomil (tak-491)', 'azilsartan medoxomil (tak-491)', 'azilsartan medoxomil (tak-491)', 'azilsartan medoxomil (tak-491)'] | ['CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1', 'CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1', 'CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1', 'CCOC1=NC2=C(N1CC1=CC=C(C=C1)C1=CC=CC=C1C1=NOC(=O)N1)C(=CC=C2)C(=O)OCC1=C(C)OC(=O)O1'] | Inclusion Criteria: For Pediatric Participants: Must have a diagnosis of hypertension (SBP and/or DBP ≥95th percentile for age/gender/height). - For Cohorts 1 and 2 only, is within the weight range of 20 kg (44 pounds) to 100 kg (220 pounds), inclusive, at Screening. - For Cohort 3 only, weighs at least 8.0 kg (17.6 pounds) at Screening. - Participants greater than or equal to 6 years of age must have the ability to swallow a tablet of the size 6.0 millimeter diameter and 3.5 millimeter thickness. - Has no known history of hepatitis B, hepatitis C, and human immunodeficiency virus. - For Cohort 3 only, may be renal transplant patient if all other inclusion and none of the exclusion criteria are met, along with additional criteria. - Must have been at a constant weight, or expected weight gain for that particular age, for 30 days with no change to the dose of their diuretic drugs. For Healthy Adult Participants: - Weighs at least 50 kilograms (110 pounds) and has a screening body mass index between 18 and 32 kilograms/m2, inclusive. - Is in good health as determined by the physician - Has a negative test result for hepatitis B surface antigen and antibody to hepatitis C virus, and has no known history of human immunodeficiency virus. - Must have a negative urine test result for selected substances of abuse . - Has a diastolic blood pressure between 60 and 90 mm Hg, inclusive, and a systolic blood pressure between 100 and 140 mm Hg, inclusive. For All Participants: - Females of child bearing potential who are sexually active, as well as sexually active male participants, agree to routinely use adequate contraception from Screening until 30 days after receiving the last dose of study medication. - Has clinical laboratory results within the reference range for the testing laboratory unless the results are deemed not clinically significant by the investigator. Exclusion Criteria: For Pediatric Participants: - Is currently treated with more than 2 antihypertensive agents. - Has sitting trough clinic systolic blood pressure greater than 15 mm Hg or diastolic blood pressure greater than 10 mm Hg above the 99th percentile for age, gender, and height at Check-in . - Has renovascular disease affecting both kidneys or a solitary kidney, dialysis treatment, severe nephrotic syndrome and not in remission. - For Cohort 1 and 2 only, a previous renal transplant. - Has a creatinine clearance less than 30 mL/min/1.73 m2. For all participants: - Has previously received azilsartan or azilsartan medoxomil. - Has a known hypersensitivity or allergy to any angiotensin type II receptor blockers or to any of the excipients in the azilsartan medoxomil formulation to be taken. - Has a history or clinical manifestations of severe cardiovascular disease, psychiatric disease, and any conditions that would interfere with gastrointestinal absorption. - Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease, cardiomyopathy, or uncorrected coarctation of the aorta. - Has been diagnosed with malignant or accelerated hypertension. - Has severe hepatic impairment. - Has a serum albumin less than 2.5 g/dL. - Has a glycosylated hemoglobin value greater than 8.5%. - Has alanine aminotransferase, aspartate aminotransferase greater than 2 times the upper limit of normal, or total bilirubin greater than 1.5 times the upper limit of normal, active liver disease, or jaundice. - Has hyperkalemia as defined by the laboratory normal reference range or any pertinent electrolyte disorders. - Is participating in another investigational study or has taken an investigational drug within 30 days prior to Check-in . - Has a history of drug abuse or a history of alcohol abuse within 1 year prior to study Check-in. - Has a history of abdominal surgery or thoracic or nonperipheral vascular surgery within 6 months prior to study Check-in. - Has a history of cancer, other than basal cell carcinoma or stage I squamous cell carcinoma of the skin that has not been in remission for at least 5 years prior to study Check-in. - Has taken any cytotoxic drugs within 12 months prior to study Check-in . - Has a history or presence of a clinically significant abnormal 12-lead electrocardiogram as determined by the investigator or sponsor/designee. - Has poor peripheral venous access. - Has any other condition or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study. - Has taken or requires the use of any medications, supplements, or food products within the stated time periods, including: - Pediatric participants taking angiotensin-converting enzyme inhibitors and other angiotensin II receptor blockers will be required to withhold these medications from the morning of Day -1 until the 24 hour pharmacokinetic sample is completed on Day 2. - Only pediatric participants will be allowed to take medications for primary renal or urologic conditions or hypertension as long as they have been on a stable dose of their medication for at least 30 days prior to Check-in (Day -1) and those medications are not potent cytochrome P-450 inhibitors or inducers. - Nutraceuticals including herbal or dietary preparations such as ginseng, kava kava, and ginkgo biloba. - Over-the-counter medications. - Vitamin supplements except for pediatric participants only. - Alcohol-containing products. - Products that contain caffeine or xanthine-related compounds. - Foods or beverages containing grapefruit juice or Seville-type oranges. |
| 100 | NCT00290719 | terminated | low enrollment | 0 | phase 1 | ['esophageal cancer'] | ["['K22.2', 'K22.81', 'Q39.4', 'P78.83', 'I85.00', 'I85.01', 'I85.10']"] | ['cisplatin', 'gefitinib', 'irinotecan hydrochloride'] | ['[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', 'COC1=C(OCCCN2CCOCC2)C=C2C(NC3=CC(Cl)=C(F)C=C3)=NC=NC2=C1', 'CCC1=C2CN3C(=CC4=C(COC(=O)[C@]4(O)CC)C3=O)C2=NC2=CC=C(OC(=O)N3CCC(CC3)N3CCCCC3)C=C12'] | DISEASE CHARACTERISTICS: - Histologically confirmed adenocarcinoma (AC) or squamous cell carcinoma of the esophagus - AC of the gastroesophageal junction allowed - Tumor must be considered surgically resectable (T1-3, NX) - No early-stage cancer (T1, N0) - The following lymph node (LN) criteria are considered acceptable: - Regional thoracic LN metastases (N1) - LN metastases levels 15 to 20 measured as ≤ 1.5 cm by CT scan - Supraclavicular LN not palpable on clinical examination measured as ≤ 1.5 cm by CT scan - No distant metastases (M0) PATIENT CHARACTERISTICS: - Platelet count ≥ 100,000/mm^3 - Absolute neutrophil count ≥ 1,500/mm^3 - Hemoglobin ≥ 9.0 g/dL - Creatinine clearance ≥ 50 mL/min - Creatinine serum level ≤ CTC grade 2 - Bilirubin ≤ 2 times upper limit of normal (ULN) - AST < 3 times ULN - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 3 months after completion of study treatment - No known severe hypersensitivity to gefitinib or any of its excipients - No evidence (except asymptomatic chronic stable radiographic changes) of clinically active interstitial lung disease - No pulmonary fibrosis, Gilbert's disease, uncontrolled diabetes mellitus, or unstable angina - No New York Heart Association class III or IV heart disease - No other concurrent malignancies or malignancies diagnosed within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix - No serious active or uncontrolled infection, systemic disease, psychiatric illness, or other medical condition that would preclude study participation - No evidence of any significant clinical disorder or laboratory finding that would preclude study participation PRIOR CONCURRENT THERAPY: - No prior chemotherapy or radiotherapy for esophageal cancer - No prior radiotherapy that would overlap the study treatment fields - Recovered from prior major surgery - No nonapproved or investigational drugs within the past 30 days - No concurrent phenytoin, carbamazepine, barbiturates, rifampin, phenobarbital, or Hypericum perforatum (St. John's wort) |