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

NCT ID: NCT02039947

Last Updated: 2019-05-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-21

Study Completion Date

2018-02-14

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Melanoma and Brain Metastases

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Cohort A

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

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Dabrafenib will be provided as 50 mg and 75 mg capsules

Trametinib

Intervention Type DRUG

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Cohort B

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

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Dabrafenib will be provided as 50 mg and 75 mg capsules

Trametinib

Intervention Type DRUG

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Cohort C

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

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Dabrafenib will be provided as 50 mg and 75 mg capsules

Trametinib

Intervention Type DRUG

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Cohort D

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

Group Type EXPERIMENTAL

Dabrafenib

Intervention Type DRUG

Dabrafenib will be provided as 50 mg and 75 mg capsules

Trametinib

Intervention Type DRUG

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Dabrafenib

Dabrafenib will be provided as 50 mg and 75 mg capsules

Intervention Type DRUG

Trametinib

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Novartis Investigative Site

Birmingham, Alabama, United States

Site Status

Novartis Investigative Site

San Francisco, California, United States

Site Status

Novartis Investigative Site

Aurora, Colorado, United States

Site Status

Novartis Investigative Site

Atlanta, Georgia, United States

Site Status

Novartis Investigative Site

Atlanta, Georgia, United States

Site Status

Novartis Investigative Site

Boston, Massachusetts, United States

Site Status

Novartis Investigative Site

Chapel Hill, North Carolina, United States

Site Status

Novartis Investigative Site

Columbus, Ohio, United States

Site Status

Novartis Investigative Site

Pittsburgh, Pennsylvania, United States

Site Status

Novartis Investigative Site

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Houston, Texas, United States

Site Status

Novartis Investigative Site

North Sydney, New South Wales, Australia

Site Status

Novartis Investigative Site

Greenslopes, Queensland, Australia

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Edmonton, Alberta, Canada

Site Status

Novartis Investigative Site

Hamilton, Ontario, Canada

Site Status

Novartis Investigative Site

Toronto, Ontario, Canada

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Boulogne-Billancourt, , France

Site Status

Novartis Investigative Site

Lille, , France

Site Status

Novartis Investigative Site

Marseille, , France

Site Status

Novartis Investigative Site

Montpellier, , France

Site Status

Novartis Investigative Site

Nantes, , France

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Pierre-Bénite, , France

Site Status

Novartis Investigative Site

Poitiers, , France

Site Status

Novartis Investigative Site

Rennes, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Novartis Investigative Site

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Novartis Investigative Site

Tübingen, Baden-Wurttemberg, Germany

Site Status

Novartis Investigative Site

Munich, Bavaria, Germany

Site Status

Novartis Investigative Site

Hanover, Lower Saxony, Germany

Site Status

Novartis Investigative Site

Cologne, North Rhine-Westphalia, Germany

Site Status

Novartis Investigative Site

Kiel, Schleswig-Holstein, Germany

Site Status

Novartis Investigative Site

Gera, Thuringia, Germany

Site Status

Novartis Investigative Site

Milan, Lombardy, Italy

Site Status

Novartis Investigative Site

Milan, Lombardy, Italy

Site Status

Novartis Investigative Site

Padua, Veneto, Italy

Site Status

Novartis Investigative Site

Barcelona, , Spain

Site Status

Novartis Investigative Site

Las Palmas de Gran Canaria, , Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Málaga, , Spain

Site Status

Novartis Investigative Site

Palma de Mallorca, , Spain

Site Status

Novartis Investigative Site

Pamplona, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Zaragoza, , Spain

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Canada France Germany Italy Spain

References

Explore related publications, articles, or registry entries linked to this study.

Syeda MM, Wiggins JM, Corless BC, Long GV, Flaherty KT, Schadendorf D, Nathan PD, Robert C, Ribas A, Davies MA, Grob JJ, Gasal E, Squires M, Marker M, Garrett J, Brase JC, Polsky D. Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study. Lancet Oncol. 2021 Mar;22(3):370-380. doi: 10.1016/S1470-2045(20)30726-9. Epub 2021 Feb 12.

Reference Type DERIVED
PMID: 33587894 (View on PubMed)

Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. doi: 10.1016/S1470-2045(17)30429-1. Epub 2017 Jun 4.

Reference Type DERIVED
PMID: 28592387 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

117277

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Radiotherapy & Combi in Metastatic Melanoma
NCT02392871 COMPLETED PHASE1/PHASE2