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) Histologic diagnosis of malignant melanoma; 3) Measurable melanoma, as per modified WHO criteria; 4) Stage III (unresectable) or Stage IV melanoma; 5) Patient must have progressed during or after at least one prior therapeutic regimen containing at least one of the following: IL-2, dacarbazine, paclitaxel, carboplatin, fotemustine, or temozolamide. 6) Have a full set of baseline (i.e., Screening) digital images of cutaneous 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 3.3.1 of the protocol. 7) Life expectancy = 16 weeks; 8) ECOG performance status of 0 or 1 (see Protocol Appendix 4); 9) 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 3.0 mg/mL); 10) 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 CRO Medical Monitor. 11) Male and female patients = 16 years of age (or minimum age of consent required per given regulatory authority); Are the trial subjects under 18? yes 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 1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire period of the study and for up to 8 weeks after the study; 2) Women who are pregnant or breastfeeding; 3) Women with a positive pregnancy test at enrollment or prior to study drug administration; 4) Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control; Target Disease Exceptions 5) Any 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, carcinoma in situ of the cervix; 6) Primary ocular or mucosal melanoma; Medical History and Concurrent Disease 7) Evidence of brain metastases on brain MRI or contrast CT; 8) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Chrohn’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 condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea; Prohibited Therapies and/or Medications 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 enrollment in another clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist; Other Exclusion Criteria 13) Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the Best Overall Response Rate (BORR), (as per modified WHO criteria) in patients with previously treated Stage III (unresectable) or Stage IV melanoma receiving ipilimumab.;Secondary Objective: 1) To estimate disease control rate (proportion of patients with best response of complete response [CR] + partial response [PR] + stable disease [SD]); 2) To estimate progression free survival (PFS) rate at Week 12; 3) To estimate PFS; 4) To estimate overall survival (OS); 5) To estimate survival rate at one year; 6) To estimate duration of best overall response (BOR) and to evaluate the proportion of patients whose duration of response is = 24 weeks; 7) To estimate time to BOR; 8) To evaluate the safety profile of ipilimumab during the Induction and Maintenance Phases; 9) To evaluate health-related quality of life (HRQoL); 10) To obtain pharmacokinetic (PK) samples for population PK analysis. ;Primary end point(s): Efficacy Measures: Investigator and Independent Review Committee (IRC) tumor evaluations will be based on modified WHO criteria. Throughout the study each respective Investigator will determine disease status of patients at the defined timepoints and as clinically indicated. For the purpose of final analysis of study results, an IRC will review all images from all timepoints for all patients and assess response parameters as specified. Pharmacokinetics: Blood draws to assess the serum PK of ipilimumab will be drawn at the time points listed in Table 7.3.5.1. Ipilimumab serum concentration data will be used in conjunction with samples from other studies as part of the population PK assessment. Serum Human Anti-Human Antibodies (HAHA) will be evaluated as described in Table 7.3.5.1. Safety Measures: Safety will be evaluated for all treated patients using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Safety assessments will be based on medical review of adverse event (AE) reports an | — |
Countries
Austria, Finland, Italy, Norway, Spain, Sweden
Outcome results
None listed