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

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:

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 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

Show 47 Study Locations

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:	September 23, 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 Trametinib Dabrafenib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2016