Advanced Cancer MedDRA version: 9.1 Level: LLT Classification code 10048683 Term: Advanced cancer
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1 1) Signed Written Informed Consent 2) Target population a) Histologically or cytologically confirmed diagnosis of solid tumor malignancy which has progressed on standard therapy or for whom no standard therapy is known; i) Minimum availability of 10 archived tumor tissue slides, or subject’s willingness and ability to undergo tumor biopsy collection for IHC analysis; either available within 28 days or greater from Cycle 1 Day 1; b) Measurable or non-measurable disease as defined by RECIST criteria; c) Adequate recovery from recent surgery and radiation therapy. At least one week must have elapsed from the time of a minor surgery and at least 3 weeks for major surgery and radiation therapy; d) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Protocol Appendix 3); e) Available for treatment and follow-up. Subjects enrolled in this trial must be treated at the participating center; f) At least four weeks must have elapsed from the last dose of carboplatin, immunotherapy or chemotherapy, (6 weeks for nitrosoureas, or mitomycin C), prior to beginning protocol therapy. Hormonal anti-cancer agents and nontraditional cytotoxic agents, such as trastuzumab, gefitinib, erlotinib, cetuximab, bevacizumab, etc., are not considered chemotherapy regimens when administered alone, and at least 4 weeks must have elapsed from the last dose of this class of agents before study drug administration. Subjects must have recovered to baseline or Grade 1 from the toxicities resulting from previous therapies. 3) Age and Sex a) Men and women, ages 18 and greater; Women of childbearing potential (WOCBP) must be using an adequate method of contraception as per the Investigator’s discretion to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized. Phase 2 includes the above inclusion criteria and the following: • Subjects with measurable, confirmed, advanced ovarian (including primary peritoneal), renal cell or breast cancer or non-measurable, confirmed, advanced ovarian (including primary peritoneal) cancer with CA125 = 2x ULN, which has progressed on standard therapy or for whom no standard therapy is known, in place of: - Histologically or cytologically confirmed diagnosis of solid tumor malignancy which has progressed on standard therapy or for whom no standard therapy is known. • IHC will be utilized to select subjects prospectively for assignment to the FR+ and FR- groups. • For subjects with renal cell cancer, up to 3 prior treatment regimens are permitted, and for subjects with ovarian or breast cancer, up to 4 prior treatment regimens are permitted. - If a treatment is stopped and restarted after a disease recurrence, that will be counted as 2 regimens. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Phase 1 1) Sex and Reproductive Status a)WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period as per Investigator’s discretion to avoid pregnancy throughout study & for up to 4 weeks after study in such a manner that risk of pregnancy is minimized b)WOCBP using a contraceptive method deemed inappropriate by Investigator c)pregnant or breastfeeding Women d)Women with positive pregnancy test on enrollment or prior to investigational product administration e)Sexually active fertile men not using effective birth control if their partners are WOCBP 2) Medical History and Concurrent Diseases a)Inability to be venipunctured &/or tolerate venous access b)Subjects with known symptomatic brain metastasis. Subjects with controlled brain metastasis will be allowed & steroid therapy may be continued. Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastasis are ruled out by CT or MRI c)CTCAE Grade 2 or greater neuropathy currently or prior history of Grade 3 or greater neuropathy d)Psychiatric disorders or other conditions rendering subject incapable of complying with requirements of protocol e)Serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by complications of this therapy f)Uncontrolled or significant cardiovascular disease, including: i)myocardial infarction within 6 months ii)uncontrolled angina within 3 months iii)congestive heart failure within 3 months iv)diagnosed or suspected congenital LQT syndrome v)any history of significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) vi) prolonged QTcF on screening or Cycle 1 Day 1 pre-dose mean (QTcF =450msec) vii)subjects with pacemaker viii)2nd degree AV block or any form of BBB ix)troponin (T or I)> institutional upper limits of normal x)LVEFClass I; g)Known MTHFR mutations or known impaired regulation of homocysteine levels; h)Uncontrolled thyroid disorder, including hypothyroidism, hyperthyroidism, Grave’s disease or Hashimoto’s disease. Subjects with hypothyroidism who are on thyroid replacement therapy & whose symptoms of thyroiditis are resolved to =Grade 1 before enrollment are eligible i)Any other sound medical, psychiatric &/or social reason as determined by Investigator 3) Physical and Laboratory Test Findings a)Inadequate hematologic function with absolute neutrophils <1,500/mm³, platelets <100,000/mm³ or hemoglobin <10g/dL b)Inadequate hepatic function with serum bilirubin=1.5 x upper institutional limits of normal, ALT = 2.5 x upper institutional limits of normal, AST =2.5 x upper institutional limits of normal c)Inadequate renal function defined as calculated creatinine clearance of <60mL/min according to Cockcroft-Gault formula: i)In men: [eGFRCG(mL/min)]=(140 - age) x weight (kg)/(72 x serum creatinine concentration in mg/dL) ii)In women, multiply this result by 0.85 d)Inadequate thyroid function with free T4 &/or TSH outside of institutional limits of normal 4) History of any significant drug allergy which in Investigator’s discretion would inhibit subject’s participation 5) Prohibited Treatments &/or Therapies a)Exposure to any investigational drug or placebo within 4 weeks of study drug administration b)Use of multi-vita
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Primary Phase 1 Objective: To determine the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended Phase 2 dose of BMS-753493 administered as a 3 to 5 minute bolus i.v. infusion on Days 1, 4, 8 and 11 of a 21-day cycle in subjects with confirmed solid tumor malignancy. • Primary Phase 2 Objective: To assess efficacy of BMS-753493 in subjects with advanced ovarian, renal or breast cancer as measured by the tumor response rate according to RECIST criteria or CA125 levels.;Secondary Objective: Secondary Phase 1 Objectives: • To describe the overall safety profile of BMS-753493 administered as a 3 to 5 minute bolus i.v. infusion on Days 1, 4, 8 and 11 of a 21-day cycle; • To assess the plasma pharmacokinetics (PK) of BMS-753493 and BMS-748285; • To evaluate the impact of BMS-753493 and BMS-748285 on QTcF; • To describe any preliminary evidence of anti-tumor activity of BMS-753493 for all treated subjects. Secondary Phase 2 Objectives: • To describe any association between anti-tumor activity and FR status as assessed by IHC; • To further characterize safety and tolerability of BMS-753493 in subjects with advanced ovarian, renal or breast cancer; • To assess the response duration and progression-free survival (PFS); • To evaluate the impact of BMS-753493 and BMS-748285 on QTcF; • To assess the PK of BMS-753493 and BMS-748285.;Primary end point(s): • Safety Outcome Measures: All subjects who receive BMS-753493 will be evaluated for safety. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, clinical laboratory tests, electrocardiograms, pulmonary function tests, and multigated radionuclide angiography (MUGA) scans or echocardiograms. Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. ECG assessments will be collected at screening (single ECG) pre-dose (trip | — |
Countries
Netherlands
Outcome results
None listed