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

Melanoma and Brain Metastases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02039947
• Other study ID #: 117277
• Status: Completed
• Phase: Phase 2
• Start date: February 21, 2014
• Est. completion date: February 14, 2018

Study information

• Verified date: May 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: February 14, 2018
• Est. primary completion date: May 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Melanoma and Brain Metastases
• Neoplasm Metastasis

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Greenslopes	Queensland
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	North Sydney	New South Wales
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
France	Novartis Investigative Site	Boulogne-Billancourt
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Marseille Cedex 5
France	Novartis Investigative Site	Montpellier cedex 5
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris Cedex 10
France	Novartis Investigative Site	Pierre-Benite cedex
France	Novartis Investigative Site	Poitiers
France	Novartis Investigative Site	Rennes Cedex
France	Novartis Investigative Site	Toulouse cedex
France	Novartis Investigative Site	Villejuif cedex
Germany	Novartis Investigative Site	Gera	Thueringen
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Heidelberg	Baden-Wuerttemberg
Germany	Novartis Investigative Site	Kiel	Schleswig-Holstein
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Muenchen	Bayern
Germany	Novartis Investigative Site	Tuebingen	Baden-Wuerttemberg
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Milano	Lombardia
Italy	Novartis Investigative Site	Padova	Veneto
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Las Palmas De Gran Canaria
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga
Spain	Novartis Investigative Site	Palma de Mallorca
Spain	Novartis Investigative Site	Pamplona
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Zaragoza
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Chapel Hill	North Carolina
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From the start of treatment until disease progression or the start of new anti-cancer therapy
Secondary	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	Approximately 2 years
Secondary	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	Approximately 2 years
Secondary	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	Approximately 2 years
Secondary	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.	Approximately 2 years
Secondary	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	From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression
Secondary	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	From the first dose to the earliest date of disease progression or death
Secondary	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	From the first dose to death