Metastatic Melanoma
Conditions
Brief summary
This is a single arm, multicenter, open label, and non-randomized clinical study on adult participants with unresectable or metastatic melanoma. The study will be conducted in two phases. Pre-screening phase will assess the BRAF V600 mutation in a new mutation analysis triggered by a mutant plasma cfDNA test result. Treatment phase will assess the clinical outcome for the participants treated with vemurafenib plus cobimetinib. The length of the study will be approximately 38 months.
Interventions
DRUGCobimetinib
Participants will receive cobimetinib 60 mg tablets (three 20 mg tablet) orally OD for 21 consecutive days (Days 1 to 21), followed by a 7 day break (Days 22 to 28); in each 28-day cycle of treatment phase until disease progression, consent withdrawal, or the development of unacceptable toxicity.
DRUGVemurafenib
Participants will receive vemurafenib 960 mg tablets (four 240 mg tablet) orally BID from Day 1 to Day 28 of each 28-day cycle of the treatment phase until disease progression, consent withdrawal, or the development of unacceptable toxicity.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pre-screening phase: * Participants with histologically confirmed cutaneous melanoma, either unresectable Stage IIIc or Stage IV metastatic melanoma, as defined by American Joint Committee on Cancer 7th edition * Documentation of BRAF V600 test result mutation-positive status on melanoma tumor tissue using a validated tissue test Treatment Phase: * Eastern Cooperative Oncology Group performance status of 0-2 * Adequate hematologic and end organ function obtained within 14 days prior to first dose of study drug treatment * Negative serum pregnancy test prior to commencement of dosing in women of childbearing potential * Absence of any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol and treatment regimen and follow-up after treatment discontinuation schedule * Female participants of childbearing potential and male participants with partners of childbearing potential must agree to always use two effective forms of contraception during the course of this study and for at least 6 months after completion of study therapy * Participants should be able to swallow tablets * Documentation of BRAF mutation positive status in melanoma tissue
Exclusion criteria
Treatment Phase: * History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment * Use of prior chemotherapy or immunotherapy (including treatment with an anti-programmed death 1, or anti- programmed death ligand 1 or anti-cytotoxic T-lymphocyte-associated protein 4 monoclonal antibody) within 4 weeks before first study drug administration * Palliative radiotherapy within 14 days prior to the first dose of study treatment * Evidence of retinal pathology on ophthalmologic examination * Systemic risk factors for retinal vein occlusion * History of clinically significant cardiac dysfunction * Current severe, uncontrolled systemic disease * Pregnancy, lactating or breast feeding * Intake of St. John's wort or hyperforin (a potent cytochrome P450 3A4 \[CYP3A4 enzyme inducer\] and grapefruit juice (a potent CYP3A4 enzyme inhibitor) at least 7 days prior to initiation of and during the study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with BRAF V600 Mutation as Assessed Using the Idylla^TM Diagnostic Platform | Days -56 to -1 (Pre-screening period) |
| Concentration of BRAF V600 Mutation as Determined on Plasma cfDNA | Days -56 to -1 (Pre-screening period) |
| Number of Participants by BRAF Mutation Status | Days -56 to -1 (Pre-screening period) |
| Number of Participants with BRAF V600 Mutation as Assessed Using the Idylla^TM Diagnostic Platform in Participants With BRAF Wild-Type Based on a Prior Tissue Test Result | Days -56 to -1 (Pre-screening period) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants with Objective Response as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Baseline up to disease progression or death whichever occurs first (up to 38 months) |
| Overall Survival | Baseline up to death (up to 38 months) |
| Progression-Free Survival (PFS) | Baseline up to disease progression or death whichever occurs first (up to 38 months) |
| Duration of Response as Assessed by Investigator According to RECIST v1.1 | Baseline up to disease progression or death whichever occurs first (Up to 38 months) |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 Cycle 1 up to 4 weeks after end of treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to 38 months) |
Countries
Belgium, Poland
Outcome results
None listed