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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02039947
First received: December 19, 2013
Last updated: August 25, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Melanoma and Brain Metastases
Drug: Dabrafenib
Drug: Trametinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Intracranial response (IR) rate [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Intracranial response rate of cohorts B, C and D [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Disease Control for intracranial, extracranial and overall response for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Extracranial response rate (ER) for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Overall response (OR) for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Duration of intracranial, extracranial and overall response for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) for each cohort [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
  • Characterize the safety of dabrafenib and trametinib in combination therapy for all cohorts. Safety will be measured by the frequency and severity of adverse events, skin assessments, laboratory abnormalities, vital signs, and assessment data. [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
    12-lead electrocardiograms (ECG), echocardiograms, and clinical monitoring/observation including neurological examination


Estimated Enrollment: 120
Study Start Date: February 2014
Estimated Study Completion Date: July 2019
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
Drug: Trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
Experimental: 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
Drug: Dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
Drug: Trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
Experimental: 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
Drug: Dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
Drug: Trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
Experimental: 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
Drug: Dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules
Drug: Trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02039947

  Hide Study Locations
Locations
United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35243
United States, California
GSK Investigational Site
San Francisco, California, United States, 94115
United States, Colorado
GSK Investigational Site
Aurora, Colorado, United States, 80045
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
GSK Investigational Site
Atlanta, Georgia, United States, 30341
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02215
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Australia, New South Wales
GSK Investigational Site
North Sydney, New South Wales, Australia, 2060
Australia, Queensland
GSK Investigational Site
Greenslopes, Queensland, Australia, 4120
Australia, Victoria
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Canada, Alberta
GSK Investigational Site
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Ontario
GSK Investigational Site
Hamilton, Ontario, Canada, L8V 5C2
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H2W 1S6
France
GSK Investigational Site
Boulogne-Billancourt, France, 92100
GSK Investigational Site
Lille, France, 59037
GSK Investigational Site
Marseille Cedex 5, France, 13385
GSK Investigational Site
Montpellier cedex 5, France, 34295
GSK Investigational Site
Nantes Cedex 1, France, 44093
GSK Investigational Site
Paris Cedex 10, France, 75475
GSK Investigational Site
Pierre-Bénite cedex, France, 69495
GSK Investigational Site
Poitiers, France, 86021
GSK Investigational Site
Rennes Cedex, France, 35042
GSK Investigational Site
Toulouse cedex, France, 31052
GSK Investigational Site
Villejuif cedex, France, 94805
Germany
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72076
GSK Investigational Site
Muenchen, Bayern, Germany, 80337
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30449
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
GSK Investigational Site
Gera, Thueringen, Germany, 07548
Italy
GSK Investigational Site
Milano, Lombardia, Italy, 20133
GSK Investigational Site
Milano, Lombardia, Italy, 20141
GSK Investigational Site
Padova, Veneto, Italy, 35128
Spain
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Las Palmas De Gran Canaria, Spain, 35016
GSK Investigational Site
Madrid, Spain, 28007
GSK Investigational Site
Málaga, Spain, 29010
GSK Investigational Site
Palma de Mallorca, Spain, 07198
GSK Investigational Site
Pamplona, Spain, 31008
GSK Investigational Site
Valencia, Spain, 46009
GSK Investigational Site
Zaragoza, Spain, 50009
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02039947     History of Changes
Other Study ID Numbers: 117277 
Study First Received: December 19, 2013
Last Updated: August 25, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
BRAF V600K mutation
Metastatic Melanoma
BRAF V600R mutation
BRAF V600D mutation
BRAF V600E mutation
Brain metastases BRAF inhibitor
Intracranial

Additional relevant MeSH terms:
Melanoma
Neoplasm Metastasis
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Dabrafenib
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 29, 2016