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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01667419




Registration number
NCT01667419
Ethics application status
Date submitted
15/08/2012
Date registered
17/08/2012
Date last updated
23/07/2019

Titles & IDs
Public title
A Study of Vemurafenib Adjuvant Therapy in Participants With Surgically Resected Cutaneous BRAF-Mutant Melanoma
Scientific title
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Vemurafenib (RO5185426) Adjuvant Therapy in Patients With Surgically Resected, Cutaneous BRAF-Mutant Melanoma at High Risk for Recurrence
Secondary ID [1] 0 0
2011-004011-24
Secondary ID [2] 0 0
GO27826
Universal Trial Number (UTN)
Trial acronym
BRIM8
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 - Vemurafenib
Treatment: Drugs - Placebo

Experimental: Cohort 1 Vemurafenib - Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib, 960 milligrams (mg) twice daily, in 28-day cycles, for up to 52 weeks

Placebo Comparator: Cohort 1 Placebo - Participants with completely resected Stage IIC, IIIA, or IIIB cutaneous melanoma) received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks

Experimental: Cohort 2 Vemurafenib - Participants with Stage IIIC cutaneous melanoma received vemurafenib, 960 mg twice daily, in 28-day cycles, for up to 52 weeks

Placebo Comparator: Cohort 2 Placebo - Participants with Stage IIIC cutaneous melanoma received vemurafenib-matching placebo twice daily, in 28-day cycles, for up to 52 weeks


Treatment: Drugs: Vemurafenib
4 tablets of vemurafenib 240 mg each (total 960 mg) were administered orally as per the schedule specified in the respective arm.

Treatment: Drugs: Placebo
Placebo matching to vemurafenib were administered orally as per the schedule specified in the respective arm.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease-Free Survival (DFS) as Assessed Using Contrast-Enhanced Magnetic Resonance Imaging (MRI) or Contrast Enhanced Computed Tomography (CT)
Timepoint [1] 0 0
From randomization until the date of the first local, regional, or distant melanoma recurrence, occurrence of new primary melanoma, or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)
Secondary outcome [1] 0 0
Distant Metastasis-Free Survival (DMFS) as Assessed Using Contrast-Enhanced MRI or Contrast Enhanced CT
Timepoint [1] 0 0
From randomization until the date of diagnosis of distant (i.e., non-locoregional) metastases or death from any cause (up to the April 17, 2017 data cut-off, approximately 4.5 years)
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From randomization until the date of death from any cause (up until 13-July-2018, approximately 6 years)
Secondary outcome [3] 0 0
Percentage of Participants With Adverse Events
Timepoint [3] 0 0
From randomization up to study completion or discontinuation (up until 13-July-2018, approximately 6 years)
Secondary outcome [4] 0 0
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) 30-Item Quality of Life Questionnaire (QLQ-C30) Score
Timepoint [4] 0 0
Day 1, Day 8, Day 15, Day 22 of Cycle 1;Day 1, Day 15 of Cycle 2;Day 1 Cycles 3-13;end of treatment(up to 13 months);every 13 weeks thereafter until recurrence or occurrence of a new primary melanoma (up to 17-Apr-17 data cut-off,approximately 4.5 years)
Secondary outcome [5] 0 0
Plasma Concentration of Vemurafenib
Timepoint [5] 0 0
Pre-morning dose (0 hour [hr]) and 1 to 4 hrs post-dose on Days 1, 8, 15, and 22 of Cycle 1; pre-morning dose (0 hr) on Days 1 and 15 of Cycle 2; pre-morning dose (0 hr) on Day 1 of Cycles 3-13; at end of treatment (up to 13 months)

Eligibility
Key inclusion criteria
- Histologically confirmed melanoma of cutaneous origin

- Participants with BRAFV600 mutation-positive, cutaneous melanoma (either pathologic
Stage IIC or Stage III according to AJCC Staging Criteria version 7 that has been
completely resected

- BRAF V600 mutation status of the current primary tumor or involved lymph node
determined to be positive using the cobas BRAF V600 mutation test

- Surgically rendered free of disease within 90 days of randomization

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Life expectancy of at least 5 years

- Fully recovered from the effects of any major surgery or significant traumatic injury
prior to the first dose of study treatment

- Adequate hematologic, hepatic, and renal function
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of any systemic or local therapy (e.g., chemotherapy, biologic or targeted
therapy, hormonal therapy, or photodynamic therapy) for the treatment or prevention of
melanoma, including interferon alpha-2b and pegylated interferon alpha-2b

- History of limb perfusion therapy

- History of radiotherapy for the treatment of melanoma

- Invasive malignancy other than melanoma at the time of enrollment or within 5 years
prior to first dose of study treatment

- Family history of inherited colon cancer syndromes

- Known personal history of >3 adenomatous colorectal polyps or a personal history of
adenomatous colorectal polyp(s) >2 centimeters (cm) in size

- History of or current clinical, radiographic, or pathologic evidence of in-transit
metastases, satellite, or microsatellite lesions

- History of or current clinical, radiographic, or pathologic evidence of recurrent
lymph node involvement after resection of a primary melanoma with lymph node
involvement at any time in the past

- History of local and/or regional and/or distant melanoma recurrence

- History or current radiographic or pathologic evidence of distant metastases

- History of clinically significant cardiac or pulmonary dysfunction

- Major surgical procedure or significant traumatic injury within 4 weeks prior to first
dose of study treatment

- Infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus

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 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
24/09/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/07/2018
Sample size
Target
Accrual to date
Final
498
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [3] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [4] 0 0
Border Medical Oncology - Wodonga
Recruitment hospital [5] 0 0
Southern Medical Day Care Centre - Wollongong
Recruitment hospital [6] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [7] 0 0
The Townsville Hospital; Townsville Cancer Centre - Townsville
Recruitment hospital [8] 0 0
Royal Adelaide Hospital; Hepatology - Adelaide
Recruitment hospital [9] 0 0
Queen Elizabeth Hospital - Woodville
Recruitment hospital [10] 0 0
Launceston General Hospital; Gastroenterology Research - Launceston
Recruitment hospital [11] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [12] 0 0
Peninsula Oncology Centre; Frankston Private - Frankston
Recruitment hospital [13] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [14] 0 0
Alfred Hospital - Melbourne
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Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
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2060 - North Sydney
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2298 - Waratah
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3690 - Wodonga
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4870 - Cairns
Recruitment postcode(s) [7] 0 0
4812 - Townsville
Recruitment postcode(s) [8] 0 0
5000 - Adelaide
Recruitment postcode(s) [9] 0 0
5011 - Woodville
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7250 - Launceston
Recruitment postcode(s) [11] 0 0
3128 - Box Hill
Recruitment postcode(s) [12] 0 0
3199 - Frankston
Recruitment postcode(s) [13] 0 0
3000 - Melbourne
Recruitment postcode(s) [14] 0 0
3004 - Melbourne
Recruitment postcode(s) [15] 0 0
6150 - Murdoch
Recruitment outside Australia
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Valencia
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Umea
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Lviv
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Kings Lynn
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Oxford
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Truro
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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
This multicenter, randomized, double-blind, placebo-controlled study will evaluate the
efficacy and safety of vemurafenib in participants with completely resected, cutaneous BRAF
mutation-positive melanoma at high risk for recurrence. Participants will be enrolled in two
separate cohorts: Cohort 1 will include participants with completely resected Stage IIC, IIIA
(participants with one or more nodal metastasis greater than [>] 1 millimeter [mm] in
diameter), or IIIB cutaneous melanoma, as defined by the American Joint Committee on Cancer
(AJCC) Classification, Version 7; Cohort 2 will include participants with Stage IIIC
cutaneous melanoma, as defined by this classification scheme. Within each cohort,
participants will be randomized (1:1 ratio) to receive vemurafenib or matching placebo over a
52-week period.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01667419
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01667419