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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
Secondary ID [1] 0 0
2011-000874-67
Secondary ID [2] 0 0
NO25390
Universal Trial Number (UTN)
Trial acronym
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 - 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD)/Recommended Dose
Timepoint [1] 0 0
Up to 28 days of treatment
Secondary outcome [1] 0 0
Area Under the Concentration-Time Curve for Vemurafenib
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Number of Participants With an Adverse Event (AE)
Timepoint [2] 0 0
Up to approximately 2 years 11 months
Secondary outcome [3] 0 0
Best Overall Response Rate (BORR)
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR)
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Progression-free Survival (PFS)
Timepoint [5] 0 0
Randomization date of first subject until disease progression or death or which ever occur first (2 years)
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
Randomization date of first subject until death (2 years)

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
Minimum age
12 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2015
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
- Westmead
Recruitment hospital [2] 0 0
- Brisbane
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
France
State/province [9] 0 0
Marseille
Country [10] 0 0
France
State/province [10] 0 0
Pierre Benite
Country [11] 0 0
Germany
State/province [11] 0 0
Kiel
Country [12] 0 0
Germany
State/province [12] 0 0
Mainz
Country [13] 0 0
Germany
State/province [13] 0 0
Tuebingen
Country [14] 0 0
Israel
State/province [14] 0 0
Jerusalem
Country [15] 0 0
Israel
State/province [15] 0 0
Petach-Tikva
Country [16] 0 0
Italy
State/province [16] 0 0
Lazio
Country [17] 0 0
Italy
State/province [17] 0 0
Liguria
Country [18] 0 0
Italy
State/province [18] 0 0
Lombardia
Country [19] 0 0
Poland
State/province [19] 0 0
Wroclaw
Country [20] 0 0
Slovakia
State/province [20] 0 0
Bratislava
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Sevilla
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Newcastle upon Tyne
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Sutton

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

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/study/NCT01519323
Trial related presentations / publications
Chisholm JC, Suvada J, Dunkel IJ, Casanova M, Zhang W, Ritchie N, Choi Y, Park J, Das Thakur M, Simko S, Wan Rachel Tam N, Ferrari A. BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib in pediatric patients with surgically incurable, BRAF mutation-positive melanoma. Pediatr Blood Cancer. 2018 May;65(5):e26947. doi: 10.1002/pbc.26947. Epub 2018 Jan 19.
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/study/NCT01519323