Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
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ClinicalTrials.gov Identifier: NCT02039947 |
Recruitment Status :
Completed
First Posted : January 20, 2014
Results First Posted : May 21, 2019
Last Update Posted : May 21, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Melanoma and Brain Metastases | Drug: Dabrafenib Drug: Trametinib | Phase 2 |
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 |

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.
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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 |
- 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.
- 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
- 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
- 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
- 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.
- 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
- 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
- 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

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.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

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