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

Phase 2CompletedNCT02039947

Novartis Pharmaceuticals127 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

127

Conditions

Melanoma and Brain Metastases

Interventions

Dabrafenib

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (47)

Novartis Investigative Site

Birmingham, Alabama, United States

Novartis Investigative Site

San Francisco, California, United States

Novartis Investigative Site

Aurora, Colorado, United States

Novartis Investigative Site

Atlanta, Georgia, United States

Novartis Investigative Site

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Intracranial Response (IR) Rate in Cohort A

The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response.

Time frame: From the start of treatment until disease progression or the start of new anti-cancer therapy

Secondary Outcomes

Intracranial Response Rate of Cohorts B, C and D

The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response. No hypothesis testing completed for cohort A, B,C and D

Time frame: Approximately 2 years

Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort

Disease Control rate is defined as the percentage of subjects achieving a confirmed intracranial/extracranial/overall CR or PR or SD or Non-CR/Non-PD. This is based on investigator-assessed response. No hypothesis testing completed for cohort A, B,C and D

Time frame: Approximately 2 years

Extracranial Response Rate (ER) for Each Cohort

Extracranial Response Rate was defined as the percentage of participants with Complete response (CR) or Partial response (PR) at anytime. This is based on investigator-assessed response. No hypothesis testing completed for cohort A,B,C and D

Time frame: Approximately 2 years

Overall Response (OR) for Each Cohort

the number of subjects with a confirmed overall Complete response (CR) or Partial response (PR) by investigator assessment using the Response evaluation criteria in solid tumors (RECIST 1.1 criteria). To determine the overall response, all target and non-target lesions will be assessed using modified RECIST 1.1 criteria.

Time frame: Approximately 2 years

Duration of Intracranial, Extracranial and Overall Response for Each Cohort

Duration of intracranial, extracranial and overall response, are defined as the time from first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression. No hypothesis testing completed for cohort A,B,C and D

Time frame: From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression

Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment

PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. No hypothesis testing completed for cohort A,B,C and D

Time frame: From the first dose to the earliest date of disease progression or death

Overall Survival (OS) for Each Cohort

Overall survival (OS) is defined as the time from the first dose until death due to any cause. No hypothesis testing completed for cohort A,B,C and D

Time frame: From the first dose to death