Patients with Metastatic or Locally Advanced Solid Malignancies MedDRA version: 9.1 Level: LLT Classification code 10025650 Term: Malignant melanoma MedDRA version: 9.1 Level: LLT Classification code 10038395 Term: Renal carcinoma MedDRA version: 9.1 Level: LLT Classification code 10033131 Term: Ovarian carcinoma
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Signed written informed consent - Target population a) Able to comply with visits/procedures required by the protocol b) Life expectancy of at least 3 months c) ECOG performance status score 0 - 1 (Protocol Appendix 4). d) Patients with histologic or cytologic diagnosis of an advanced solid malignancy who have failed, refused or are unable to receive standard treatment. NOTE: Patients enrolled after Amendment 7 is IRB approved are limited to: • Melanoma (must be anti-CTLA-4 naive), • Renal (clear cell) carcinoma, or • Epithelial carcinoma arising from the ovary, fallopian tube or peritoneum. e) At least 1 site of measurable disease (excluding epithelial carcinoma who must have at least 1 site of “evaluable” disease) f) A tumor paraffin embedded tissue block or 5 - 15 unstained slides from the tumor tissue block (from the primary or a metastatic tumor) must be provided for biomarker and predictive marker analyses. Note: If the tumor tissue block or unstained slides are not available or insufficient, additional fresh tumor tissue could be collected during the optional pretreatment biopsy to satisfy this criteria g) At least 4 weeks must have elapsed since the last chemotherapy, immunotherapy, hormonal therapy, radiotherapy or major surgery, & the 1st day of BMS-663513 therapy. At least 6 weeks for nitrosoureas, mitomycin C & liposomal doxorubicin h) Toxicities related to prior therapy must either have returned to = Grade 1, baseline or deemed irreversible -Age and Sex a) Men and women, who are at least 18 years of age. - Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche & who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 IU/mL. Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (eg, vasectomy), should be considered to be of child bearing potential. - WOCBP must have a negative pregnancy test [minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadatrophin (ßHCG)] within 72-hours prior to the start of study medication. - Physical and laboratory test findings: a) Adequate bone marrow function defined as: Absolute neutrophil count (ANC) >= 1,500 cells/mm³ Platelet count >= 100,000 cells/mm³ Hemoglobin >= 9.0 g/dl b) Adequate hepatic function defined as: Total bilirubin == 60 mL/min/1.73m² 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: - Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study. b) WOCBP using a prohibited contraceptive method. c) Women who are pregnant or breastfeeding. d) Women with a positive pregnancy test on enrollment or prior to study drug administration. e) Sexually active fertile men, whose partners are WOCBP, who are unwilling or unable to use an acceptable method of birth control from the time of enrollment and for 12 weeks after participation in the study. - Medical History and Concurrent Diseases a) Active infection or uncontrolled significant acute or chronic medical illness other than current cancer that would prohibit safe administration of BMS-663513. b) Any concurrent malignancy other than adequately treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for >= 5 years will be allowed to enter the trial. c) History of autoimmune diseases including rheumatoid arthritis, lupus erythermatosus, uveitis and autoimmune inflammatory eye disease, psoriasis, multiple sclerosis, inflammatory bowel diseases, etc. Type I diabetes mellitus is allowed. d) Known or suspected human immunodeficiency virus (HIV) positive. e) Any current condition requiring the continued use of systemic or topical steroids or the use of immunosuppressive agents (eg, cyclosporine and its analog, or chemotherapy agents). All corticosteroid use must have been discontinued >= 4 weeks prior to Day 1 of treatment. f) Active/symptomatic brain metastasis. Patients with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by computerized axial tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastasis and those who were previously treated with radiotherapy or surgery must have no current evidence of active/symptomatic brain metastasis and are off steroid therapy for at least 4 weeks prior to Day 1 of treatment. g) Uncontrolled or significant cardiovascular disease including myocardial infarction within 6 months, uncontrolled angina, Class III-IV New York Heart Association (NYHA) congestive heart failure (Appendix 5) and clinically significant ventricular arrhythmias. h) Any other sound medical, psychiatric and/or social reason, which in the opinion of the principal investigator, would prohibit the understanding of the informed consent and/or make the administration of study drug hazardous or obscure the interpretation of adverse events. i) History of hepatitis B or C, or alcohol induced liver disease. - Physical and Laboratory Test Findings a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations. b) Positive blood screen for hepatitis B surface antigen, or hepatitis C antibody. - Allergies and Adverse Drug Reactions a) History of allergy to BMS-663513 or related compounds. - Prohibited Therapies and/or Medications a) Exposure to any investigational products within 4 weeks prior to Day 1 of treatment. b) Use of any immunosuppressing treatments including corticosteroids, cyclosporine, mycophenolate mofetil (CellCept®), chemotherapy, radiation, etc, within 4 weeks prior to Day 1 of treatment. -Other Exclusion Criteria a) Prisoners or patients w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of BMS-663513 in the range of 0.3 mg/kg to 15 mg/kg administered once every 3 weeks to patients with metastatic or locally advanced solid malignancies in the dose escalation portion of the study. To estimate the reversible Grade 3-4 toxicity rate in the expanded dose cohorts of melanoma, ovarian and renal carcinoma patients at each of the 3 selected doses (1, 3 and 10 mg/kg).;Secondary Objective: •Assess the PK of BMS-663513 •Assess BMS-663513 dose & biologic effect relationships using: -Flow cytometry to quantitate subsets of immune cells (CD3, CD4, CD8, CD19, & CD16/56) -Flow cytometry to measure subsets of T cells (activated, memory) -QRT-PCR to measure changes in RNA expression in peripheral blood -ELISA to measure changes in levels of cytokines &/or other biomolecules •Screen for anti-tumor activity of single agent BMS-663513 •Assess the effect of BMS-663513 on immune response to non-cancer vaccines (influenza, tetanus, pneumoccocal) •Assess the immunogenic potential of BMS-663513 •Assess the effect of BMS-663513 on intratumoral immune response pre and post treatment using immunohistochemistry •Obtain fresh & paraffin embedded tumor samples, & blood, to identify potential predictive markers of biological response utilizing ribonucleic acid (RNA) profiling, protein profiling, single nucleotide polymorphism (SNP) analysis, & other techniques;Primary end point(s): • Primary Safety Outcome Measures: Safety assessments will be based on medical review of adverse event (AE) reports and the results of vital sign measurements, EKG/ECG, physical examinations, and clinical laboratory tests. AEs will be recorded using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 and the incidence will be tabulated and reviewed for potential significance and clinical importance. • Pharmacokinetic Measures: PK parameters (Cmax, Cmin, Tmax, AUC(INF), AUC(TAU), T1/2, CLT, Vss, and ?x) may be derived from se | — |
Countries
France
Outcome results
None listed