BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations

This study has been terminated.
(Study was terminated due to low enrollment.)
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01519323
First received: January 16, 2012
Last updated: June 17, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Malignant Melanoma
Drug: vemurafenib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD)/Recommended Dose [ Time Frame: Up to 28 days of treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Area Under the Concentration-Time Curve for Vemurafenib [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days) ] [ Designated as safety issue: No ]
  • Number of Participants With an Adverse Event (AE) [ Time Frame: Up to approximately 2 years 11 months ] [ Designated as safety issue: No ]
    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.

  • Best Overall Response Rate (BORR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.

  • Clinical Benefit Rate (CBR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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). CBR was summarized along with the associated exact 95% CI using the method of Clopper-Pearson.

  • Progression-free Survival (PFS) [ Time Frame: Randomization date of first subject until disease progression or death or which ever occur first (2 years) ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) [ Time Frame: Randomization date of first subject until death (2 years) ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: January 2013
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: vemurafenib
Cohort 1 (participants >=45 kg): starting dose level 720mg; next dose level 960 mg Cohort 2 (participants <45 kg): starting dose 480 mg
Other Name: Zelboraf

  Eligibility

Ages Eligible for Study:   12 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519323

  Show 26 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01519323     History of Changes
Other Study ID Numbers: NO25390  2011-000874-67 
Study First Received: January 16, 2012
Results First Received: June 17, 2016
Last Updated: June 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on July 28, 2016