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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02039947
Recruitment Status : Completed
First Posted : January 20, 2014
Results First Posted : May 21, 2019
Last Update Posted : May 21, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Melanoma and Brain Metastases Drug: Dabrafenib Drug: Trametinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: Non-Randomized
Masking: None (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
Actual Study Start Date : February 21, 2014
Actual Primary Completion Date : May 12, 2017
Actual Study Completion Date : February 14, 2018

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Intracranial Response (IR) Rate in Cohort A [ Time Frame: From the start of treatment until disease progression or the start of new anti-cancer therapy ]
    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.


Secondary Outcome Measures :
  1. Intracranial Response Rate of Cohorts B, C and D [ Time Frame: Approximately 2 years ]
    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

  2. Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort [ Time Frame: Approximately 2 years ]
    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

  3. Extracranial Response Rate (ER) for Each Cohort [ Time Frame: Approximately 2 years ]
    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

  4. Overall Response (OR) for Each Cohort [ Time Frame: Approximately 2 years ]
    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.

  5. Duration of Intracranial, Extracranial and Overall Response for Each Cohort [ Time Frame: From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression ]
    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

  6. Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment [ Time Frame: From the first dose to the earliest date of disease progression or death ]
    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

  7. Overall Survival (OS) for Each Cohort [ Time Frame: From the first dose to death ]
    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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02039947


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

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] March 5, 2018
Study Protocol  [PDF] June 21, 2017

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02039947    
Other Study ID Numbers: 117277
First Posted: January 20, 2014    Key Record Dates
Results First Posted: May 21, 2019
Last Update Posted: May 21, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
BRAF V600K mutation
Metastatic Melanoma
BRAF V600R mutation
BRAF V600D mutation
BRAF V600E mutation
Brain metastases BRAF inhibitor
Intracranial
Additional relevant MeSH terms:
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Trametinib
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
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action