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

NCT01519323 | Terminated Phase 1 Results DMC

• 2 other identifiers: NO253902011-000874-67
• Study Type: interventional
• Target: 6
• Locations: 10 countries
• Sites: 26

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.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)/Recommended Dose

  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.

  Up to 28 days of treatment

Secondary Outcomes (6)

• Area Under the Concentration-Time Curve for Vemurafenib

  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)

• Number of Participants With an Adverse Event (AE)

  Up to approximately 2 years 11 months

• Best Overall Response Rate (BORR)

  Up to 2 years

• Clinical Benefit Rate (CBR)

  Up to 2 years

• Progression-free Survival (PFS)

  Randomization date of first subject until disease progression or death or which ever occur first (2 years)

Study Arms (1)

Vemurafenib

EXPERIMENTAL

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

Interventions

vemurafenib DRUG

Cohort 1 (participants \>=45 kg): starting dose level 720mg; next dose level 960 mg Cohort 2 (participants \<45 kg): starting dose 480 mg

Also known as: Zelboraf

Vemurafenib

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (26)

Unknown Facility

Los Angeles, California, 90027, United States

Location

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Aurora, Colorado, 80045, United States

Location

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Saint Petersburgh, Florida, 33701, United States

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Bethesda, Maryland, 20892, United States

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Boston, Massachusetts, 02115, United States

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New York, New York, 10065, United States

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Memphis, Tennessee, 38105, United States

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Houston, Texas, 77030, United States

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Westmead, New South Wales, 2145, Australia

Location

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Brisbane, Queensland, 4029, Australia

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Marseille, 13385, France

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Pierre-Bénite, 69495, France

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Kiel, 24116, Germany

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Mainz, 55101, Germany

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Tübingen, 72076, Germany

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Jerusalem, 9112001, Israel

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Petah Tikva, 49100, Israel

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Rome, Lazio, 00165, Italy

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Genoa, Liguria, 16147, Italy

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Milan, Lombardy, 20133, Italy

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Wroclaw, 50-367, Poland

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Bratislava, 83340, Slovakia

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Esplugues de Llobregas, Barcelona, 08950, Spain

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Seville, Sevilla, 41013, Spain

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Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

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Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 29350463 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was prematurely terminated on 18 December 2015 by the Sponsor due to recruitment challenges and therefore low enrollment.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: January 26, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 10, 2016
• Results First Posted: July 28, 2016

Record last verified: 2016-08

Locations

FR (2); SL (1); IL (2); PL (1); AU (2); US (8); IT (3); ES (2); GB (2); DE (3)