Histologically Confirmed Stage III (unresectable) or Stage IV Melanoma MedDRA version: 17.0 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0 Level: PT Classification code 10025670 Term: Malignant melanoma stag
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care. b) Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study. 2. Target Population a) Subjects with histologically confirmed malignant melanoma b) Eastern Cooperative Oncology Group (ECOG) Performance Status: i) PS 0 to 1 (Cohort 1) ii) PS 2 (Cohort 2; maximum of 300; clinical risk benefit ratio of Cohort 2 will be monitored by the Scientific Steering Committee and evaluated after treatment of n = 50 for at least 2 months) c) Previously treated unresectable stage III or stage IV melanoma as per the American Joint Committee on Cancer 2010 Guidelines 30 regardless of BRAF mutation status d) Subjects must have experienced evaluable RECIST 1.1-defined evaluable disease progression e) Prior treatment with chemotherapy, interferon (adjuvant setting), IL-2, BRAF/MEK inhibitors for subjects with known BRAF mutations, MEK inhibitors for NRAS mutations, and cKIT inhibitor subjects with known cKIT mutations are allowed f) Subjects are eligible if CNS metastases are treated and subjected are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids or on a stable or decreasing dose of or equal 2000/microL ii) Neutrophils > or equal 1500/microL iii) Platelets> or equal 100 x 10³/microL iv) Hemoglobin > or equal 9.0 g/dL v) Serum creatinine of 40 mL/minute (using Cockcroft/Gault formula) (1) Female CrCl= [(140- age in years) x weight in kg x 0.85) ÷(72 x serum creatinine in mg/ dL)] (2) Male CrCl= [(140- age in years) x weight in kg x 1.00) ÷(72 x serum creatinine in mg/ dL)] vi) AST < or equal 3 X ULN vii)ALT < or equal 3 X ULN viii) Total bilirubin < or equal 1.5
Exclusion criteria
Exclusion criteria: 1. Target Disease Exceptions a) Leptomeningeal metastases are excluded b) Subjects with untreated, active CNS metastases are excluded 2. Medical History and Concurrent Diseases a) Subjects with active, known, or suspected autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. b) Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease. c) Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder cancer, gastric or colon cancers, cervical cancers/dysplasia or breast carcinoma in situ) are excluded unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required or anticipated to be required during the study period d) Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy e) Any treatment in a nivolumab trial or treatment in an ipilimumab trial f) Known drug or alcohol abuse 3. Physical and Laboratory Test Findings a) Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection b) Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) 4. Allergies and Adverse Drug Reaction a) History of severe hypersensitivity reactions to other monoclonal antibodies b) History of allergy or intolerance (unacceptable adverse event) to study drug components or Polysorbate-80-containing infusions. c) Subjects with a known history of the following anti-CTLA-4 therapy related adverse reactions based on the CTCAE v4.0 criteria: i. Grade > or equal 3 anti-CTLA-4 therapy-related adverse reaction except resolved nausea, fatigue, or endocrinopathies where clinical symptoms were able to be controlled with appropriate hormone replacement therapy ii. Any > or equal Grade 2 eye pain or reduction of visual acuity that did not respond to topical therapy and did not improve to ? Grade 1 severity within 2 weeks of starting topical therapy or required systemic treatment iii. Any > or equal Grade 3 sensory neurologic toxicity iv. Any Grade 4 laboratory abnormalities, except AST, ALT, or T. bilirubin: a) AST or ALT > 10 x ULN b) T. bilirubin > 5 x ULN v. Subjects who required infliximab or other immune suppressants including mycophenolic acid for management of drug-related toxicities vi. Any other anti-CTLA-4 therapy-related adverse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial are: - To determine the rate and frequency of high-grade (CTCAE v4.0 Grade 3 or higher), treatment-related, select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-CTLA-4 monoclonal antibody, treated with nivolumab (BMS-936558) at a dose of 3 mg/kg every two weeks for a maximum of 24 months. ; Secondary Objective: The secondary objectives: - To characterize the outcome (duration of treatment and grade of resolution) of high-grade (CTCAE v4.0 Grade 3 or higher), select adverse events in subjects with histologically confirmed stage III (unresectable) or stage IV melanoma and progression post prior treatment containing an anti-CTLA-4 monoclonal antibody, treated with nivolumab (BMS-936558) at a dose of 3 mg/kg every 2 weeks for a maximum of 24 months. - To estimate overall survival (OS) in all treated subjects - To estimate Investigator-assessed best overall response (BOR) Exploratory objectives: Refer to study protocol ; Primary end point(s): The primary endpoints include: - Rate and frequency for high-grade (CTCAE v4.0 Grade 3 or higher) treatment-related, select adverse events - Rate and frequency of AEs regardless of causality - Rate and frequency of treatment-related AEs - Rate and frequency of any AEs of special interest (AEOSI), such as pulmonary, gastrointestinal, cutaneous, renal, hepatic, pancreatic, endocrine, infusion related, or hypersensitivity ;Timepoint(s) of evaluation of this end point: up to 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints include: - Outcome (grade of resolution; duration of AE-specific treatment) of all high-grade (CTCAE v4.0 Grade 3 or higher) treatment-related adverse events - Time to OS and survival at Years 1 and 2 after treatment and beyond. - Investigator-assessed BOR The exploratory endpoints include: - Safety, tolerability, OS, and Investigator-assessed BOR in subjects with BRAF-mutated melanoma - Safety, tolerability, OS, and Investigator-assessed BOR in subjects with inactive brain metastasis - Safety, tolerability, OS, and Investigator-assessed BOR in subjects with Performance Status (0-1 or 2) - Safety, tolerability, OS, and Investigator-assessed BOR in patients with uveal/ocular and mucosal melanoma - Quality of Life as mean and change from baseline in domain scores and health status index based on EORTC-QLQ-C30 and EQ-5D of the full safety analysis set ;Timepoint(s) of evaluation of this end point: up to 24 months | — |
Countries
Austria, Belgium, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Malta, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed