MELANOMA MedDRA version: 9.1 Level: LLT Classification code 10025670 Term: Malignant melanoma stage III MedDRA version: 9.1 Level: LLT Classification code 10025671 Term: Malignant melanoma stage IV
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Voluntary signed and dated IRB/IEC approved informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before performing protocol-related procedures that are not part of standard subject care. 2) Target Population a) Able to comply with visits/procedures required by the protocol. b) Life expectancy of at least 3 months from enrollment c) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Protocol Appendix 2) d) Histologically or cytologically confirmed cutaneous, mucosal or acral lentiginous melanoma that is radiographically assessable or clinically evaluable; however, measurable disease is not required for participation in this study e) Surgically incurable Stage III melanoma, and in-transit or satellite lesions or Stage IV disease, metastatic to one of the following sites: skin, subcutaneous tissues, or distant lymph nodes; lung or other visceral sites f) Subjects must have been previously treated with one line of systemic anti-cancer therapy (non-experimental or experimental) for metastatic disease, and relapsed, failed to respond (CR, PR or SD) or did not tolerate that regimen. If the treatment has been administered as an adjuvant and/or neoadjuvant therapy, the subject must have documented disease progression from the last treatment and also received one additional line of systemic therapy for metastatic disease g) Resolution of all prior therapy-related toxicities to = Grade 1 or to baseline level h) Recovered from the reversible effects of prior antineoplastic therapy with at least 4 weeks elapsed since the last exposure to cytotoxic chemotherapy, or to radiotherapy and at least 6 weeks elapsed since exposure to nitrosoureas or mitomycin C. Subjects treated with fully human anti-CTLA-4 monoclonal antibodies as immunotherapy regimens (eg, ipilimumab and tremelimumab) must not have received treatment with such antibodies for at least 8 weeks, and those treated with chimeric or other fully human monoclonal antibodies must not have received treatment with such antibodies for at least 4 weeks prior to randomization. Subjects previously treated with cytokines (eg interferons or IL-2) or noncytotoxic small molecule drugs (eg, tyrosine kinase inhibitors) must not have received treatment with these drugs at the time of enrollment and at least 2 weeks prior to randomization. i) Suitable venous access for the conduct of blood sampling for candidate biomarker study j) Adequate organ function, as evidence by the following laboratory values: • Absolute neutrophil count (ANC) = 1500/µL • Platelet count = 100 x 103/µL • Hemoglobin = 9 g/dL • Calculated creatinine clearance = 40 mL/min based on Cockcroft-Gault or other available formula. • AST and ALT = 2.5 x ULN • Total bilirubin = 1.5 x ULN 3) Age and Sex a) Men and women, who are at least 18 years of age. b) Male subjects must be willing to use an appropriate method of barrier contraception (eg, condoms) and inform any sexual partners that they must also use a reliable method of contraception (eg, birth control pills) during the study and for 60 days after the last dose of study treatment. c) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 60 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized. WOCBP include any female who h
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study and for up to 60 days after the last dose of investigational product. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration d) Sexually active fertile men not using effective birth control if their partners are WOCBP (eg, males unwilling to use a barrier method of contraception) 2) Target Disease Exceptions a) Ocular melanoma b) Complete surgical resection of all identifiable sites of disease c) Symptomatic brain metastasis. Subjects 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). Subjects with stable brain metastasis and those who were previously treated with radiotherapy or surgery must have no current evidence of symptomatic brain metastasis and are off steroid therapy for at least 4 weeks prior to randomization. d) Any other malignancy for which the subject has been disease-free for less than 5 years, with the exception of adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix, breast or prostate 3) Medical History and Concurrent Diseases a) Histories of autoimmune diseases including Inflammatory Bowel Disease, Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease are excluded from this study. Note that not all autoimmune diseases are to be excluded, and subjects with a history of well-controlled and/or clinically manageable autoimmune disease (eg, vitiligo, well-controlled thyroid disease, or mild psoriasis) may be considered for inclusion in consultation with the Medical Monitor b) Known or suspected human immunodeficiency virus (HIV) infection or known or suspected active or chronic hepatitis B or hepatitis C infection. If false positive results are obtained, the subject can enter the study after discussion and agreement between the Investigator and the Medical Monitor. c) Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug. d) Clinically significant abnormalities or serious cardiac arrhythmias on 12-lead electrocardiogram (ECG). Significant cardiovascular impairment (eg, history of congestive heart failure), New York Heart Association (NYHA) (Appendix 3) Class III and IV or history of myocardial infarction or unstable angina within the past six months or significant vascular disease (eg, aortic aneurysm or aortic dissection) e) History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization f) Prior treatment with radiation therapy within 4 weeks involving > 25% of the hematopoietically active bone marrow 4) 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) Bodyweight of less then 85 lbs (38.5 Kg) 5) Allergies and Adverse Drug Reactions a) History of allergy to BMS-663513 or related compounds 6) Prohibited Treatments and/or Therapies a) Received more than one line of prior systemic therapies including cytotoxic chemotherapy; non-cytoxic sma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the 6-month PFS rate following treatment with BMS-663513 in each arm.;Primary end point(s): The primary endpoint in this study is PFS rate at 6 months. Kaplan-Meier methods, which account for censoring, will be used for analyses of the 6-month PFS rate. ;Secondary Objective: The secondary objectives of this study include the following: • To estimate the PFS distribution and median PFS time in each arm • To estimate the tumor response rate in each arm • To estimate the disease control rate in each arm, ie, the proportion of subjects with a complete response (CR), a partial response (PR), or with stable disease (SD) that lasts for at least 24 weeks • To collect exploratory response data beyond disease progression • To estimate the overall survival distribution and 1-year survival rate in each arm • To estimate time to and duration of response for each arm • To evaluate the safety profile for each arm • To assess a population PK of BMS-663513 for each arm • To evaluate the exploratory pharmacodynamic and predictive biomarkers in serum, peripheral blood mononuclear cells (PBMCs), whole blood, or tumor tissue (if applicable) • To assess the immunogenicity of BMS-663513 on inducing serum Human Anti Human Antibodies (HAHA). | — |
Countries
Denmark, France, Germany, Italy
Outcome results
None listed