Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

Novartis

Status and phase: Completed; Phase 2

Conditions: Melanoma and Brain Metastases

Treatments: Drug: Dabrafenib; Drug: Trametinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02039947

117277

Details and patient eligibility

About

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.

Enrollment: 127 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

127 participants in 4 patient groups

Cohort A

Experimental group

Description:

Subjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity.

Treatment:

Drug: Dabrafenib

Drug: Trametinib

Cohort B

Experimental group

Description:

Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

Treatment:

Drug: Dabrafenib

Drug: Trametinib

Cohort C

Experimental group

Description:

Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

Treatment:

Drug: Dabrafenib

Drug: Trametinib

Cohort D

Experimental group

Description:

Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

Treatment:

Drug: Dabrafenib

Drug: Trametinib