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 August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02039947
First received: December 19, 2013
Last updated: August 14, 2014
Last verified: August 2014

December 19, 2013
August 14, 2014
February 2014
January 2015   (final data collection date for primary outcome measure)
Intracranial response (IR) rate [ Time Frame: Approximately 2 years ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT02039947 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
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

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma and Brain Metastases
  • 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 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.
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
  • 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
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
  • 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
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
  • 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
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
January 2015
January 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
United States,   Australia,   Canada,   France,   Italy,   Spain
 
NCT02039947
117277
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP