Phase 2 Study testing the COmbination of Vemurafenib With Cobimetinib in BRAF V600 mutated Melanoma Patients to Normalize LDH and Optimize immunotherapY with Nivolumab and Ipilimumab (COWBOY)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 200

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 * 2x ULN
o AST, ALT * 2.5 x ULN (*5 x ULN for patients with liver
metastases)
o Bilirubin *2 X ULN
o LDH > ULN, < 3xULN
* No symptomatic brain metastases (asysmptomatic brain metastases, accidentally
found during screening can be included)
* No leptomeningeal metastases
* No active autoimmune disease requiring systemic treatment in the past 3
months or a documented history of autoimmune disease, or history of syndrome
that required systemic steroids, at daily dose of *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

Not applicable

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Compare the best overall response rate (BORR) according to RECIST 1.1 of both<br /><br>arms at week 18 from start of treatment.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Progression-free survival (PFS) according to RECIST 1.1<br /><br>- Overall survival (OS)<br /><br>- Percentage of grade 3/4 toxicities according to CTCv4.03<br /><br>- Percentage of ongoing response, percentage of patients requiring<br /><br>re-induction, response percentage upon reinduction<br /><br>- Changes in tumor-specific T cell responses</p><br>

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