Melanoma skin cancer
Conditions
Interventions
Melanoma
Immunotherapy
Patients will be randomized 1:1 to receive either 6 weeks vemurafenib 960 mg
bid 28 day + cobimetinib 60 mg QD 21-day on, 7-day off (21/7) schedule,
directly followed by 4 courses of ipilimumab 3mg/
COWBOY
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: In order to participate in this study, a subject must meet all of the following criteria:;• Adults 18 years and older ;• World Health Organization (WHO) Performance Status 0-2;• Histologically or cytologically confirmed Stage IV, or unresectable stage III, BRAF V600E/K mutated melanoma;• Measurable disease according to RECIST 1.1;• Signed and dated informed consent form;• No prior immunotherapy targeting CTLA-4, PD-1 or PD-L1;• No prior BRAFi and/ or MEKi therapy;• No immunosuppressive medications;• Screening laboratory values must meet the following criteria and should be obtained within 10 days prior to randomization:;o WBC >= 2.0x109/L, Neutrophils >= 1.0x109/L, Platelets >= 100 x109/L, Hemoglobin >= 5.0mmol/L;o Creatinine ULN, =10mg prednisone or equivalent, or immunosuppressive medications. (Subjects with vitiligo or resolved childhood asthma/atopy are excluded from this rule (and will not be excluded from this study). Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen*s syndrome will not be excluded from the study.);• No evidence of interstitial lung disease or active, non-infectious pneumonitis;• No active infection requiring therapy;• No known additional malignancy that is progressing or requires active treatment;• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days + the time required for nivolumab to undergo five half-lives) after the last dose of study medication;• WOBCP must have a negative serum or urine pregnancy test within 96 hours prior to the start of study treatment and must not be breast feeding;• Men must agree to the use of male contraception during the study treatment period and for at least 31 weeks after the last dose of study drug.;• Currently not participating in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.;• No underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events
Exclusion criteria
Exclusion criteria: Not applicable
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| • Compare the best overall response rate (BORR) according to RECIST 1.1 of both arms at week 18 from start of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Progression-free survival (PFS) according to RECIST 1.1 • Overall survival (OS) • Percentage of grade 3/4 toxicities according to CTCv4.03 • Percentage of ongoing response, percentage of patients requiring re-induction, response percentage upon re-induction • Changes in tumor-specific T cell responses | — |
Countries
The Netherlands
Outcome results
None listed