Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Vemurafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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.

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

vemurafenib

Clinical Trials

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.

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

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

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.

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.

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.

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).

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 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.

Hoffmann-La Roche

An AE was defined as any untoward medical occurrence in a participant administered the investigational product which does not necessarily have a causal relationship with this treatment.

Age, Continuous

Sex: Female, Male

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

Medical Communications

A MTD could not be determined in this study because of the low number of participants enrolled.

Maximum Tolerated Dose (MTD)/Recommended Dose

Cycle 1 Day 1

Cycle 1 Day 22

Participants enrolled in the first cohort received vemurafenib 720 mg by mouth BID.

Vemurafenib 720 mg

Participants enrolled in the second cohort received vemurafenib 960 mg by mouth BID.

Vemurafenib 960 mg

Pharmacokinetic (PK) population included all enrolled participants who received at least one dose or a partial dose of study treatment and provided at least one post-dose blood sample for PK analysis.

Area Under the Concentration-Time Curve for Vemurafenib

Safety population included all participants who received at least one dose or a partial dose of study treatment.

Number of Participants With an Adverse Event (AE)

Intent to treat population included all participants enrolled.

Best Overall Response Rate (BORR)

Clinical Benefit Rate (CBR)

Progression-free Survival (PFS)

Overall Survival (OS)

Participants received 720 milligram (mg) of vemurafenib by mouth twice daily (BID).

Vemurafenib Dose Escalation Cohort Level 1

Participants received 960 mg of vemurafenib by mouth BID.

Spots Global Cancer Trial Database for BRIM-P: A Study of Vemurafenib in Pediatric Patients With Stage IIIC or Stage IV Melanoma Harboring BRAFV600 Mutations

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial