| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10027156 |
| E.1.2 | Term | Skin melanomas (excl ocular) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to determine the 6-month PFS rate following treatment with BMS-663513 in each arm |
|
| E.2.2 | Secondary objectives of the trial |
| 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) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 treated with 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 |
|
| E.4 | Principal exclusion criteria |
| - 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 - Women who are pregnant or breastfeeding - Women with a positive pregnancy test on enrollment or prior to investigational product administration - Sexually active fertile men not using effective birth control if their partners are WOCBP (eg, males unwilling to use a barrier method of contraception) -Ocular melanoma - Complete surgical resection of all identifiable sites of disease c) Clinical and/or radiographic evidence of cerebral or subdural metastases and/or progression of central nervous system (CNS) metastases within the past 4 weeks. Subjects who have a history of CNS metastasis but have no radiographic (eg, brain MRI or contrast CT) or clinical evidence of residual tumor (eg, following complete surgical resection) are excluded from participation in this study based on the following: – Required the use of corticosteroid therapy or DCVax®-Brain for this indication – Discontinue treatment for < 4 weeks before randomization in this study - 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 - 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 - 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. - 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. - 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) -History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization f) Prior treatment with radiation therapy within 4 weeks involving more than 25% of the hematopoietically active bone marrow - Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations. - Bodyweight of less then 85 lbs (38.5 Kg) - History of allergy to BMS-663513 or related compounds - Received more than one line of prior systemic therapies including cytotoxic chemotherapy; non-cytoxic small molecular drugs, biologics or radiation therapy for metastatic disease (note: adjuvant and/or neoadjuvant therapy is allowed and will not be counted as one line of prior therapy) - Initiation of growth factor treatment such as granulocyte-colony stimulating factor (G-CSF), or granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 28 days prior to randomization. - Prior treatment with high-dose chemotherapy, defined as chemotherapy requiring the use of peripheral blood or bone marrow stem cell support for hematopoietic reconstitution or with organ allografts requiring immunosuppression |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
