Previously treated unresectable Stage III or IV Melanoma
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Willing and able to give written informed consent; 2) Histologically confirmed malignant melanoma; 3) Measurable melanoma, as per modified WHO criteria; 4) Stage III (unresectable) or Stage IV melanoma; 5) Patient must have demonstrated one of the following in response to treatment with at least one prior regimen (non-experimental or experimental) with the exception of a CD137 agonist or CTLA-4 inhibitor or agonist: 1) relapse following an objective response of PR or CR; or 2) failed to demonstrate an objective response of PR or CR based on an assessment period of at least 12 weeks from prior regimen start; or 3) inability to tolerate treatment due to toxicity; 6) Have a complete set of baseline (i.e., Screening) digital images of lesions and radiographic images, including, but not limited to: brain, bone, chest, abdomen and pelvis. All images must be of adequate quality as detailed in Section 3.3 of the protocol; 7) Required values for initial laboratory tests: • WBC = 2500/uL • ANC = 1000/uL • Platelets = 75 x 103/uL • Hemoglobin = 9 g/dL • Creatinine = 2.5 x ULN • AST = 3 x ULN for patients without liver metastasis = 5 x ULN for patients with liver metastasis • Bilirubin = 3 x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3 mg/mL); 8) ECOG performance status of 0 or 1; 9) Life expectancy of = 16 weeks; 10) Accessible for treatment and follow-up; 11) Negative screening tests for HIV, HepB, and HepC. If positive results are not indicative of true active or chronic infection, the patient can enter the study after discussion and agreement between the Investigator and the Medical Monitor; 12) Male and female patients = 16 years of age (or minimum age of consent required per given regulatory authority); Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. 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: 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study. 2) Women who are pregnant or breastfeeding 3) Women with a positive pregnancy test on enrollment or prior to study drug administration. 4) Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control; 5) Evidence of brain metastases on brain imaging (i.e., MRI or contrast CT); 6) Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix; 7) Primary ocular or mucosal melanoma; 8) Autoimmune disease: Patients with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]); 9) Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study medication hazardous to the patient, obscure the interpretation of adverse events (such as a condition associated with frequent diarrhea) or may render the patient incapable of complying with the requirements of the study; 10) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of study drug); surgery or radiotherapy (except as described in Sections 6.2.8.3 and 6.2.8.4); other investigational anti-cancer therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses); 11) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; 12) Previous treatment in another ipilimumab clinical trial or prior treatment with a CD137 agonist, CTLA-4 inhibitor or agonist; 13) Inability to provide adequate informed consent; 14) Prisoners or subjects who are compulsorily detained.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate best overall response rate (BORR) (as per modified WHO criteria) in patients with previously treated, therapy-refractory or -intolerant, Stage III (unresectable) or Stage IV melanoma receiving ipilimumab doses of 0.3, 3, and 10 mg/kg.;Secondary Objective: 1) To evaluate the dose-response relationship based on BORR; 2) To estimate the difference in BORR in patients receiving 3 vs. 0.3 mg/kg, 10 vs. 0.3 mg/kg and 10 vs. 3 mg/kg; 3) To estimate progression free survival (PFS) rate at the Week 12 assessment; 4) To estimate disease control rate (proportion with best response of CR + PR + SD); 5) To estimate PFS; 6) To estimate overall survival (OS); 7) To estimate survival rate at one year; 8) To estimate duration of BOR and define the proportion of patients with duration of response lasting = 24 weeks; 9) To estimate time to BOR; 10) To evaluate the safety profile of ipilimumab during the Induction and Maintenance Phase at each dosage level of ipilimumab; 11) To evaluate HRQoL; 12) To obtain PK samples for population PK analysis;;Primary end point(s): Efficacy Analyses The efficacy analyses will be performed when the last randomized patient has been followed to Week 24. Efficacy analyses in all randomized patients will be performed as randomized. The BORR will be estimated in each randomized arm, and the corresponding exact two-sided 95% confidence interval will be computed using the method of Clopper and Pearson. Two sided 95% confidence intervals for all pairwise differences in BORR (3 vs. 0.3 mg/kg, 10 vs. 0.3 mg/kg, and 10 vs. 3 mg/kg) will be computed using the method of DerSimonian and Laird. A one-sided exact Cochran-Armitage trend test with a 0.05 significance level will be used to evaluate whether a positive dose-response relationship based on the BORRs in the randomized arms. BORR subgroup analyses will be performed by the following baseline variables: age (65), race (White, Black, Asian, Other), gender (male, female), M stage (M0, | — |
Countries
Belgium, Czech Republic, Germany, United Kingdom
Outcome results
None listed