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

NCT02039947 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 117277
• Study Type: interventional
• Target: 127
• Locations: 7 countries
• Sites: 47

Brief 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.

Conditions

Melanoma and Brain Metastases

Keywords

BRAF V600K mutation; Metastatic Melanoma; BRAF V600R mutation; BRAF V600D mutation; BRAF V600E mutation; Brain metastases BRAF inhibitor; Intracranial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Intracranial Response Rate of Cohorts B, C and D

  Approximately 2 years

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

  Approximately 2 years

• Extracranial Response Rate (ER) for Each Cohort

  Approximately 2 years

• Overall Response (OR) for Each Cohort

  Approximately 2 years

• Duration of Intracranial, Extracranial and Overall Response for Each Cohort

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

Study Arms (4)

Cohort A

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.

Drug: Dabrafenib; Drug: Trametinib

Cohort B

EXPERIMENTAL

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

Drug: Dabrafenib; Drug: Trametinib

Cohort C

EXPERIMENTAL

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

Drug: Dabrafenib; Drug: Trametinib

Cohort D

EXPERIMENTAL

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

Drug: Dabrafenib; Drug: Trametinib

Interventions

Dabrafenib DRUG

Dabrafenib will be provided as 50 mg and 75 mg capsules

Cohort A; Cohort B; Cohort C; Cohort D

Trametinib DRUG

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Cohort A; Cohort B; Cohort C; Cohort D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (47)

Novartis Investigative Site

Birmingham, Alabama, 35243, United States

Location

Novartis Investigative Site

San Francisco, California, 94115, United States

Location

Novartis Investigative Site

Aurora, Colorado, 80045, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30341, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02215, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

Novartis Investigative Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37232, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

North Sydney, New South Wales, 2060, Australia

Location

Novartis Investigative Site

Greenslopes, Queensland, 4120, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Novartis Investigative Site

Hamilton, Ontario, L8V 5C2, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1S6, Canada

Location

Novartis Investigative Site

Boulogne-Billancourt, 92100, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Marseille, 13385, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Pierre-Bénite, 69495, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Rennes, 35042, France

Location

Novartis Investigative Site

Toulouse, 31052, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Novartis Investigative Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Novartis Investigative Site

Munich, Bavaria, 80337, Germany

Location

Novartis Investigative Site

Hanover, Lower Saxony, 30449, Germany

Location

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Novartis Investigative Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

Novartis Investigative Site

Gera, Thuringia, 07548, Germany

Location

Novartis Investigative Site

Milan, Lombardy, 20133, Italy

Location

Novartis Investigative Site

Milan, Lombardy, 20141, Italy

Location

Novartis Investigative Site

Padua, Veneto, 35128, Italy

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Las Palmas de Gran Canaria, 35016, Spain

Location

Novartis Investigative Site

Madrid, 28007, Spain

Location

Novartis Investigative Site

Málaga, 29010, Spain

Location

Novartis Investigative Site

Palma de Mallorca, 07198, Spain

Location

Novartis Investigative Site

Pamplona, 31008, Spain

Location

Novartis Investigative Site

Valencia, 46009, Spain

Location

Novartis Investigative Site

Zaragoza, 50009, Spain

Location

Related Publications (2)

• 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.

  PMID: 33587894 DERIVED

• 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.

  PMID: 28592387 DERIVED

MeSH Terms

Conditions

Melanoma; Brain Neoplasms

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceutical

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2013
• First Posted: January 20, 2014
• Study Start: February 21, 2014
• Primary Completion: May 12, 2017
• Study Completion: February 14, 2018
• Last Updated: May 21, 2019
• Results First Posted: May 21, 2019

Record last verified: 2019-05

Locations

DE (7); US (11); IT (3); AU (3); CA (4); ES (8); FR (11)