Clinical trial NCT01519323: BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Malignant Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-01-26
Enrollment: 6
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)/Recommended Dose
timeFrame: Up to 28 days of treatment
Secondary outcomes:
measure: Area Under the Concentration-Time Curve for Vemurafenib
timeFrame: 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)
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to approximately 2 years 11 months
measure: Best Overall Response Rate (BORR)
timeFrame: Up to 2 years
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 2 years
measure: Progression-free Survival (PFS)
timeFrame: Randomization date of first subject until disease progression or death or which ever occur first (2 years)
measure: Overall Survival (OS)
timeFrame: Randomization date of first subject until death (2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: St. Petersburgh
country: United States
state: Florida
city: Bethesda
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: New York
country: United States
state: New York
city: Memphis
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Westmead
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Marseille
country: France
city: Pierre Benite
country: France
city: Kiel
country: Germany
city: Mainz
country: Germany
city: Tuebingen
country: Germany
city: Jerusalem
country: Israel
city: Petach-Tikva
country: Israel
city: Roma
country: Italy
state: Lazio
city: Genova
country: Italy
state: Liguria
city: Milano
country: Italy
state: Lombardia
city: Wroclaw
country: Poland
city: Bratislava
country: Slovakia
city: Esplugues De Llobregas
country: Spain
state: Barcelona
city: Sevilla
country: Spain
city: Newcastle upon Tyne
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.