Back to resultsA 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
Primary Purpose
Metastatic Melanoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cobimetinib
Vemurafenib
Sponsored by
About this trial
This is an interventional screening trial for Metastatic Melanoma
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
Sites / Locations
- UZ Brussel
- Institut Jules Bordet
- CHIREC Edith Cavell
- UZ Antwerpen
- UZ Gent
- Jessa Zkh (Campus Virga Jesse)
- AZ Groeninge
- Clinique Ste-Elisabeth
- AZ Delta (Campus Wilgenstraat)
- AZ Nikolaas (Sint Niklaas)
- Sint Augustinus Wilrijk
- Klinika Onkologii Klinicznej CO-I Kraków
- Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
- Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Phase: Vemurafenib+Cobimetinib
Arm Description
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.
Outcomes
Primary Outcome Measures
Number of Participants with BRAF V600 Mutation as Assessed Using the Idylla^TM Diagnostic Platform
Concentration of BRAF V600 Mutation as Determined on Plasma cfDNA
Number of Participants by BRAF Mutation Status
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
Secondary Outcome Measures
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)
Progression-Free Survival (PFS)
Duration of Response as Assessed by Investigator According to RECIST v1.1
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Overall Survival
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02768207
Brief Title
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
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
May 23, 2016 (Actual)
Primary Completion Date
December 20, 2017 (Actual)
Study Completion Date
June 27, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma
7. Study Design
Primary Purpose
Screening
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Phase: Vemurafenib+Cobimetinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cobimetinib
Other Intervention Name(s)
GDC-0973, RO5514041, XL518
Intervention Description
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
Intervention Name(s)
Vemurafenib
Other Intervention Name(s)
RO5185426
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants with BRAF V600 Mutation as Assessed Using the Idylla^TM Diagnostic Platform
Time Frame
Days -56 to -1 (Pre-screening period)
Title
Concentration of BRAF V600 Mutation as Determined on Plasma cfDNA
Time Frame
Days -56 to -1 (Pre-screening period)
Title
Number of Participants by BRAF Mutation Status
Time Frame
Days -56 to -1 (Pre-screening period)
Title
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
Time Frame
Days -56 to -1 (Pre-screening period)
Secondary Outcome Measure Information:
Title
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)
Time Frame
Baseline up to disease progression or death whichever occurs first (up to 38 months)
Title
Progression-Free Survival (PFS)
Time Frame
Baseline up to disease progression or death whichever occurs first (up to 38 months)
Title
Duration of Response as Assessed by Investigator According to RECIST v1.1
Time Frame
Baseline up to disease progression or death whichever occurs first (Up to 38 months)
Title
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
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)
Title
Overall Survival
Time Frame
Baseline up to death (up to 38 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
UZ Brussel
City
Brussel
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Institut Jules Bordet
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
CHIREC Edith Cavell
City
Bruxelles
ZIP/Postal Code
1180
Country
Belgium
Facility Name
UZ Antwerpen
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Jessa Zkh (Campus Virga Jesse)
City
Hasselt
ZIP/Postal Code
3500
Country
Belgium
Facility Name
AZ Groeninge
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Clinique Ste-Elisabeth
City
Namur
ZIP/Postal Code
5000
Country
Belgium
Facility Name
AZ Delta (Campus Wilgenstraat)
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Facility Name
AZ Nikolaas (Sint Niklaas)
City
Sint Niklaas
ZIP/Postal Code
9100
Country
Belgium
Facility Name
Sint Augustinus Wilrijk
City
Wilrijk
ZIP/Postal Code
2610
Country
Belgium
Facility Name
Klinika Onkologii Klinicznej CO-I Kraków
City
Krakow
Country
Poland
Facility Name
Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
City
Poznań
ZIP/Postal Code
60-780
Country
Poland
Facility Name
Centrum Onkologii- Instytut; im. M.Skłodowskiej-Curie
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs