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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

NCT02039947

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Study to Evaluate Treatment of <span class="go-doc-concept go-doc-intervention">Dabrafenib</span> Plus <span class="go-doc-concept go-doc-intervention">Trametinib</span> in Subjects With <span class="go-doc-concept go-doc-alteration">BRAF Mutation</span>-Positive <span class="go-doc-concept go-doc-disease">Melanoma</span> That Has Metastasized to the Brain

Title

  • Brief Title: Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
  • 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
  • Clinical Trial IDs

    NCT ID: NCT02039947

    ORG ID: 117277

    Trial Conditions

    Melanoma and Brain Metastases

    Trial Interventions

    Drug Synonyms Arms
    Dabrafenib Cohort B, Cohort C, Cohort A, Cohort D
    Trametinib Cohort B, Cohort C, Cohort A, Cohort D

    Trial 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cohort A Experimental Subjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity. Dabrafenib, Trametinib
    Cohort B Experimental Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity Dabrafenib, Trametinib
    Cohort C Experimental Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity Dabrafenib, Trametinib
    Cohort D Experimental Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity Dabrafenib, Trametinib

    Eligibility 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 nave 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Intracranial response (IR) rate

    Secondary Outcome Measures

    Intracranial response rate of cohorts B, C and D

    Disease Control for intracranial, extracranial and overall response for each cohort

    Extracranial response rate (ER) for each cohort

    Overall response (OR) for each cohort

    Duration of intracranial, extracranial and overall response for each cohort

    Progression-free survival (PFS) for each cohort

    Overall survival (OS) for each cohort

    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.

    Trial Keywords

    Metastatic Melanoma

    BRAF V600K mutation

    BRAF V600R mutation

    BRAF V600E mutation

    BRAF V600D mutation

    Brain metastases BRAF inhibitor

    Intracranial