Clinical trial NCT02768207: A Study to Detect V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) V600 Mutation on Cell-Free Deoxyribonucleic Acid (cfDNA) From Plasma in Participants With Advanced Melanoma
Official title: A Single Arm, Open Label, Phase II, Multicenter Study to Assess The Detection of The BRAF V600 Mutation on cfDNA From Plasma in Patients With Advanced Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-05-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with BRAF V600 Mutation as Assessed Using the Idylla^TM Diagnostic Platform
timeFrame: Days -56 to -1 (Pre-screening period)
measure: Concentration of BRAF V600 Mutation as Determined on Plasma cfDNA
timeFrame: Days -56 to -1 (Pre-screening period)
measure: Number of Participants by BRAF Mutation Status
timeFrame: Days -56 to -1 (Pre-screening period)
measure: 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
timeFrame: Days -56 to -1 (Pre-screening period)
Secondary outcomes:
measure: 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)
timeFrame: Baseline up to disease progression or death whichever occurs first (up to 38 months)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to disease progression or death whichever occurs first (up to 38 months)
measure: Duration of Response as Assessed by Investigator According to RECIST v1.1
timeFrame: Baseline up to disease progression or death whichever occurs first (Up to 38 months)
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Overall Survival
timeFrame: Baseline up to death (up to 38 months)
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Bruxelles
country: Belgium
facility: CHIREC Edith Cavell
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Wilgenstraat)
city: Sint Niklaas
country: Belgium
facility: AZ Nikolaas (Sint Niklaas)
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Krakow
country: Poland
facility: Klinika Onkologii Klinicznej CO-I Kraków
city: Poznań
country: Poland
facility: Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
city: Warszawa
country: Poland
facility: Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: