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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01689519




Registration number
NCT01689519
Ethics application status
Date submitted
18/09/2012
Date registered
21/09/2012
Date last updated
11/05/2020

Titles & IDs
Public title
A Study Comparing Vemurafenib Versus Vemurafenib Plus Cobimetinib in Participants With Metastatic Melanoma
Scientific title
A Phase III, Double-Blind, Placebo-Controlled Study of Vemurafenib Versus Vemurafenib Plus GDC-0973 in Previously Untreated BRAF^600-Mutation Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma
Secondary ID [1] 0 0
2012-003008-11
Secondary ID [2] 0 0
GO28141
Universal Trial Number (UTN)
Trial acronym
coBRIM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Vemurafenib
Treatment: Drugs - Cobimetinib

Active Comparator: Placebo + Vemurafenib - Participants will receive placebo orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 milligrams (mg) orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.

Experimental: Cobimetinib + Vemurafenib - Participants will receive cobimetinib 60 mg orally once daily on Days 1-21 of each 28-day cycle plus vemurafenib 960 mg orally twice a day on Days 1-28 of each 28-day cycle until disease progression, death, unacceptable toxicity, or withdrawal of consent, whichever occurs earliest.


Treatment: Drugs: Placebo
Placebo supplied as tablets

Treatment: Drugs: Vemurafenib
Vemurafenib supplied as tablets

Treatment: Drugs: Cobimetinib
Cobimetinib supplied as tablets

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival - Progression-free survival was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator using Response Evaluation Criteria in Solid Tumors v1.1, or death from any cause, whichever came first. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Timepoint [1] 0 0
Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Secondary outcome [1] 0 0
Overall Survival - Overall survival was defined as the time from randomization until the date of death from any cause.
Timepoint [1] 0 0
Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Secondary outcome [2] 0 0
Percentage of Participants With an Objective Response - An objective response was defined as a complete response or a partial response determined on two consecutive occasions = 4 weeks apart. Responses were determined by Response Evaluation Criteria in Solid Tumors v1.1. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
Timepoint [2] 0 0
Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Secondary outcome [3] 0 0
Duration of Response - Duration of response was defined as the time from first occurrence of a documented confirmed objective response until the time of disease progression, as determined by investigator review of tumor assessments using Response Evaluation Criteria in Solid Tumors v1.1 or death from any cause during the study. Disease progression was defined as: (1) at least a 20% increase in the sum (the increase in the sum must be at least 5 mm) of diameters of target lesions, taking as reference the smallest sum during the study; (2) unequivocal progression of existing non-target lesions; or (3) the appearance of 1 or more new lesions.
Timepoint [3] 0 0
Baseline to the 09 May 2014 data cut-off (up to 1 year, 4 months)
Secondary outcome [4] 0 0
Overall Survival (Final Analysis) - Overall survival was defined as the time from randomization until the date of death from any cause.
Timepoint [4] 0 0
Baseline to the 28 August 2015 Overall Survival data cut-off (up to 2 years, 8 months)

Eligibility
Key inclusion criteria
- Participants with histologically confirmed melanoma, either unresectable stage IIIc or
stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th
edition. Unresectability of stage IIIc disease must have confirmation from a surgical
oncologist

- Participants must be naïve to treatment for locally advanced unresectable or
metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease;
stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed

- Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival
or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test

- Measurable disease per RECIST v1.1

- Eastern Clinical Oncology Group performance status of 0 or 1

- Consent to provide archival for biomarker analyses

- Consent to undergo tumor biopsies for biomarker analyses

- Life expectancy greater than or equal to (=) 12 weeks

- Adequate hematologic and end organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase
pathway inhibitor treatment

- Palliative radiotherapy within 14 days prior to the first dose of study treatment

- Major surgery or traumatic injury within 14 days prior to first dose of study
treatment

- Active malignancy other than melanoma that could potentially interfere with the
interpretation of efficacy measures. Participants with a previous malignancy within
the past 3 years are excluded except for participants with resected basal cell
carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ
of the cervix, and carcinoma in-situ of the breast

- History of or evidence of retinal pathology on ophthalmological examination that is
considered a risk factor for neurosensory retinal detachment, retinal vein occlusion,
or neovascular macular degeneration

- Uncontrolled glaucoma with intraocular pressure

- Serum cholesterol = Grade 2

- Hypertriglyceridemia = Grade 2

- Hyperglycemia (fasting) = Grade 2

- History of clinically significant cardiac dysfunction

- Participants with active central nervous system (CNS) lesions (including carcinomatous
meningitis) are excluded. However, participants are eligible if:

1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND

2. There has been no evidence of clinical and radiographic disease progression in
the CNS for = 3 weeks after radiotherapy or surgery

- Current severe, uncontrolled systemic disease

- History of malabsorption or other condition that would interfere with absorption of
study drugs

- Pregnant, lactating, or breast feeding women

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Lake Macquarie Private Hospital - Gateshead
Recruitment hospital [3] 0 0
Lismore Base Hospital; Cancer Care & Haematology Unit - Lismore
Recruitment hospital [4] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [5] 0 0
Royal Darwin Hospital - Casuarina
Recruitment hospital [6] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [7] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 0 0
Royal Adelaide Hospital; Hepatology - Adelaide
Recruitment hospital [10] 0 0
Ashford Cancer Centre - Ashford SA
Recruitment hospital [11] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [12] 0 0
Launceston General Hospital; Gastroenterology Research - Launceston
Recruitment hospital [13] 0 0
Peninsula and South Eastern Haematology and Oncology Group - Frankston
Recruitment hospital [14] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [15] 0 0
Peter MacCallum Cancer Centre-East Melbourne - Melbourne
Recruitment hospital [16] 0 0
The Alfred Hospital - Prahan
Recruitment hospital [17] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2290 - Gateshead
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2480 - Lismore
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2060 - North Sydney
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0811 - Casuarina
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4120 - Greenslopes
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4029 - Herston
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [9] 0 0
5000 - Adelaide
Recruitment postcode(s) [10] 0 0
5035 - Ashford SA
Recruitment postcode(s) [11] 0 0
7000 - Hobart
Recruitment postcode(s) [12] 0 0
7250 - Launceston
Recruitment postcode(s) [13] 0 0
3199 - Frankston
Recruitment postcode(s) [14] 0 0
3084 - Heidelberg
Recruitment postcode(s) [15] 0 0
3000 - Melbourne
Recruitment postcode(s) [16] 0 0
3181 - Prahan
Recruitment postcode(s) [17] 0 0
6150 - Murdoch
Recruitment outside Australia
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Tennessee
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Linz
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St. Pölten
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Wien
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Bruxelles
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Edegem
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Hasselt
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Liège
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Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared
with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients
with unresectable locally advanced or metastatic melanoma, as measured by progression-free
survival (PFS), assessed by the study site investigator.
Trial website
https://clinicaltrials.gov/show/NCT01689519
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications