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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02039947
First received: December 19, 2013
Last updated: July 10, 2014
Last verified: July 2014
  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:


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: January 2015
Estimated Primary Completion Date: January 2015 (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
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

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 31 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02039947     History of Changes
Other Study ID Numbers: 117277
Study First Received: December 19, 2013
Last Updated: July 10, 2014
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
Brain Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

ClinicalTrials.gov processed this record on July 23, 2014