Overview

This trial is active, not recruiting.

Condition melanoma and brain metastases
Treatments dabrafenib, trametinib
Phase phase 2
Targets BRAF, MEK
Sponsor GlaxoSmithKline
Start date February 2014
End date May 2017
Trial size 120 participants
Trial identifier NCT02039947, 117277

Summary

This is a multi-cohort, open label, Phase II study with Dabrafenib (GSK2118436) and Trametinib (GSK1120212) combination therapy in subject with BRAF mutation-positive melanoma that has metastasized to the brain. This study will evaluate the safety and efficacy of 4 cohorts. Cohorts will consist of; V600 E, D, K, R mutations, metastases to the brain, symptomatic and asymptomatic, with or without prior local (brain) therapy, with or without prior local (brain) therapy, and range of ECOG scores from 0-2.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Subjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity.
dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
(Experimental)
Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
(Experimental)
Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
(Experimental)
Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Primary Outcomes

Measure
Intracranial response (IR) rate
time frame: Approximately 2 years

Secondary Outcomes

Measure
Intracranial response rate of cohorts B, C and D
time frame: Approximately 2 years
Disease Control for intracranial, extracranial and overall response for each cohort
time frame: Approximately 2 years
Extracranial response rate (ER) for each cohort
time frame: Approximately 2 years
Overall response (OR) for each cohort
time frame: Approximately 2 years
Duration of intracranial, extracranial and overall response for each cohort
time frame: Approximately 2 years
Progression-free survival (PFS) for each cohort
time frame: Approximately 2 years
Overall survival (OS) for each cohort
time frame: Approximately 2 years
Characterize the safety of dabrafenib and trametinib in combination therapy for all cohorts. Safety will be measured by the frequency and severity of adverse events, skin assessments, laboratory abnormalities, vital signs, and assessment data.
time frame: Approximately 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - ECOG Performance Status range of 0-2 - Histologically confirmed cutaneous metastatic melanoma of V600 E, K, D or R. - May be systemic naïve or received up to two previous systemic treatment regimens for metastatic melanoma. - Must be able to undergo MRI and have at least one measurable intracranial lesion for which specific criteria have to be met. Exclusion Criteria: - Prior treatment with any BRAF inhibitor or any mitogen-activated protein/extracellular signal-regulated kinase inhibitor. - Anti-cancer therapy or investigational anti-cancer therapy or chemotherapy without delayed toxicity within treatment specific timeframe. - Treatment with stereotactic radiosurgery or treatment with whole-brain radiation within treatment specific timeframe. - Any presence of leptomeningeal disease or any parenchymal brain metastasis - History of another malignancy, some exceptions may apply. - A history or evidence of cardiovascular risk- specific criteria have to be met - A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.

Additional Information

Official title BRF117277: A Phase II, Open-Label, Multicentre Study of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.