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

NCT ID: NCT02768207

Last Updated: 2019-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-23
• Study Completion Date: 2019-06-27

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.

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

Treatment Phase: Vemurafenib+Cobimetinib

Participants with BRAF V600 mutation will receive vemurafenib 960 milligrams (mg) tablets orally twice daily (BID) on Days 1 to 28 along with cobimetinib 60 mg tablets orally once daily (OD) for 21 consecutive days (Days 1 to 21) of each 28-day cycle until disease progression, consent withdrawal, or the development of unacceptable toxicity.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

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.

Vemurafenib

Intervention Type: DRUG

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.

Interventions

Cobimetinib

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.

Intervention Type: DRUG

Vemurafenib

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.

Intervention Type: DRUG

Other Intervention Names

GDC-0973, RO5514041, XL518; RO5185426

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Institut Jules Bordet

Brussels, , Belgium

UZ Brussel

Brussels, , Belgium

CHIREC Edith Cavell

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZ Gent

Ghent, , Belgium

Jessa Zkh (Campus Virga Jesse)

Hasselt, , Belgium

AZ Groeninge

Kortrijk, , Belgium

Clinique Ste-Elisabeth

Namur, , Belgium

AZ Delta (Campus Wilgenstraat)

Roeselare, , Belgium

AZ Nikolaas (Sint Niklaas)

Sint-Niklaas, , Belgium

Sint Augustinus Wilrijk

Wilrijk, , Belgium

Klinika Onkologii Klinicznej CO-I Kraków

Krakow, , Poland

Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.

Poznan, , Poland

Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie

Warsaw, , Poland

Countries

Belgium; Poland

Other Identifiers

2015-001731-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ML29741

Identifier Type: -

Identifier Source: org_study_id