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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/NCT01519323
Registration number
NCT01519323
Ethics application status
Date submitted
16/01/2012
Date registered
26/01/2012
Date last updated
10/10/2016
Titles & IDs
Public title
BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations
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Scientific title
An Open-label, Multicenter, Single-arm, Phase I Dose-escalation With Efficacy Tail Extension Study of Vemurafenib (RO5185426) in Pediatric Patients With Surgically Incurable and Unresectable Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations
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Secondary ID [1]
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2011-000874-67
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Secondary ID [2]
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NO25390
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - vemurafenib
Experimental: Vemurafenib - Participants received vemurafenib into two separate cohorts with different starting doses based on greater than or equal to (>=)45 kilogram (kg) and other weighing less than (<)45 kg. The starting dose for participants (>=45 kg) was 720 milligram (mg) of vemurafenib by mouth twice daily (BID) and the next dose level for participants in this cohort was 960 mg by mouth BID. The starting dose level for participants weighing <45 kg was to be 480 mg of vemurafenib by mouth BID, but no participants were enrolled into this cohort.
Treatment: Drugs: vemurafenib
Cohort 1 (participants >=45 kg): starting dose level 720mg; next dose level 960 mg Cohort 2 (participants <45 kg): starting dose 480 mg
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Maximum Tolerated Dose (MTD)/Recommended Dose
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Assessment method [1]
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The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
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Timepoint [1]
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Up to 28 days of treatment
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Secondary outcome [1]
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Area Under the Concentration-Time Curve for Vemurafenib
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Assessment method [1]
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Timepoint [1]
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Pre-dose, 2, 4, 8, 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days)
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Secondary outcome [2]
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Number of Participants With an Adverse Event (AE)
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Assessment method [2]
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An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment.
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Timepoint [2]
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Up to approximately 2 years 11 months
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Secondary outcome [3]
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Best Overall Response Rate (BORR)
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Assessment method [3]
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BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants who achieved a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.
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Timepoint [3]
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Up to 2 years
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Secondary outcome [4]
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Clinical Benefit Rate (CBR)
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Assessment method [4]
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CBR was defined as the number of participants that achieved a CR, PR or stable disease (SD) (SD for at least 6 weeks) as assessed by investigators according to the RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as at >=30% decrease under baseline of the sum of diameters of all target lesions. SD was defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
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Timepoint [4]
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Up to 2 years
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Secondary outcome [5]
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Progression-free Survival (PFS)
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Assessment method [5]
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PFS was defined as the time between the day of first treatment and the first documentation of progressive disease or death. Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Participants who were withdrawn from the study without documented progression were to be censored at the date of the last known tumor assessment when the participant was known to be progression free. Median PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
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Timepoint [5]
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Randomization date of first subject until disease progression or death or which ever occur first (2 years)
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Secondary outcome [6]
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Overall Survival (OS)
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Assessment method [6]
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Overall survival was defined as the time between the date of first treatment to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of their last being known alive. Median overall survival was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
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Timepoint [6]
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Randomization date of first subject until death (2 years)
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Eligibility
Key inclusion criteria
- Pediatric participants, 12 to 17 years of age inclusive
- Histologically confirmed surgically incurable and unresectable Stage IIIC or Stage IV
(AJCC) melanoma
- Positive proto-oncogene B-Raf (BRAF) mutation result (Cobas 4800 BRAF V600 Mutation
Test)
- Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST)
criteria
- Performance status: Karnofsky (for participants >/= 16 years of age) or Lansky (for
participants < 16 years of age) score of >/= 60
- Adequate bone marrow, liver and renal function
- Participants must have fully recovered from the acute toxic effects of all prior
therapy prior to first administration of study drug
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Minimum age
12
Years
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Maximum age
17
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Active or untreated central nervous system (CNS) lesions
- History of or known spinal cord compression or carcinomatous meningitis
- Anticipated or ongoing administration of anti-cancer therapies other than those
administered in this study
- Previous malignancy within the past 5 years except for basal or squamous cell
carcinoma of the skin, melanoma in-situ, and carcinoma in-situ of the cervix
- Previous treatment with selective/specific BRAF or Methyl Ethyl Ketone (MEK) inhibitor
(previous treatment with sorafenib is allowed)
- Any previous treatment with study drug (RO5185426) or participation in a clinical
trial that includes RO5185426
- Pregnant or lactating females
- Known human immunodeficiency virus (HIV) positivity or acquired immune deficiency
syndrome (AIDS)-related illness, active hepatitis B virus, or active hepatitis C virus
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/01/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/12/2015
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Sample size
Target
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Accrual to date
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Final
6
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Recruitment in Australia
Recruitment state(s)
NSW,QLD
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Recruitment hospital [1]
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- Westmead
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Recruitment hospital [2]
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- Brisbane
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment postcode(s) [2]
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4029 - Brisbane
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Recruitment outside Australia
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United States of America
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State/province [1]
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California
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United States of America
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Colorado
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United States of America
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Florida
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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New York
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United States of America
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Tennessee
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United States of America
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Texas
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France
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Marseille
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France
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State/province [10]
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Pierre Benite
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Germany
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Kiel
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Germany
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Mainz
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Germany
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Tuebingen
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Israel
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Jerusalem
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Israel
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State/province [15]
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Petach-Tikva
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Italy
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State/province [16]
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Lazio
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Italy
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Liguria
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Italy
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Lombardia
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Poland
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Wroclaw
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Slovakia
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Bratislava
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Spain
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Barcelona
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Spain
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Sevilla
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
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Sutton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail
extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy
of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly
diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma
harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until
disease progression or unacceptable toxicity occurs.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01519323
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Email
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01519323
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