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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 127
- Locations
- 1
- Primary Endpoint
- Intracranial Response (IR) Rate in Cohort A
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Dabrafenib (Drug)
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.
Intervention: Trametinib (Drug)
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
Intervention: Dabrafenib (Drug)
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
Intervention: Trametinib (Drug)
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
Intervention: Dabrafenib (Drug)
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
Intervention: Trametinib (Drug)
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
Intervention: Dabrafenib (Drug)
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
Intervention: Trametinib (Drug)
Outcomes
Primary Outcomes
Intracranial Response (IR) Rate in Cohort A
Time Frame: From the start of treatment until disease progression or the start of new anti-cancer therapy
The intracranial response rate is defined as the percentage of subjects achieving a confirmed intracranial CR or PR. This is based on investigator-assessed best intracranial response.
Secondary Outcomes
- Intracranial Response Rate of Cohorts B, C and D(Approximately 2 years)
- Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort(Approximately 2 years)
- Extracranial Response Rate (ER) for Each Cohort(Approximately 2 years)
- Overall Response (OR) for Each Cohort(Approximately 2 years)
- Duration of Intracranial, Extracranial and Overall Response for Each Cohort(From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression)
- Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment(From the first dose to the earliest date of disease progression or death)
- Overall Survival (OS) for Each Cohort(From the first dose to death)