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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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02039947
First Posted: January 20, 2014
Last Update Posted: October 3, 2017
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.
Information provided by (Responsible Party):
Novartis
  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
Intervention Model: Parallel Assignment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Intracranial response (IR) rate [ Time Frame: Approximately 2 years ]

Secondary Outcome Measures:
  • Intracranial response rate of cohorts B, C and D [ Time Frame: Approximately 2 years ]
  • Disease Control for intracranial, extracranial and overall response for each cohort [ Time Frame: Approximately 2 years ]
  • Extracranial response rate (ER) for each cohort [ Time Frame: Approximately 2 years ]
  • Overall response (OR) for each cohort [ Time Frame: Approximately 2 years ]
  • Duration of intracranial, extracranial and overall response for each cohort [ Time Frame: Approximately 2 years ]
  • Progression-free survival (PFS) for each cohort [ Time Frame: Approximately 2 years ]
  • Overall survival (OS) for each cohort [ Time Frame: Approximately 2 years ]
  • 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 ]
    12-lead electrocardiograms (ECG), echocardiograms, and clinical monitoring/observation including neurological examination


Enrollment: 126
Actual Study Start Date: February 21, 2014
Estimated Study Completion Date: December 15, 2017
Primary Completion Date: May 12, 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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
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


  Show 47 Study Locations
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT02039947     History of Changes
Other Study ID Numbers: 117277
First Submitted: December 19, 2013
First Posted: January 20, 2014
Last Update Posted: October 3, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis:
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
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action