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:

MedlinePlus related topics: Melanoma

Drug Information available for: Trametinib Dabrafenib

Genetic and Rare Diseases Information Center resources: Carcinoid Tumor Neuroepithelioma

U.S. FDA Resources

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

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