Phase 2
N=125
Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
Melanoma and Brain Metastases
Bottom Line
View on ClinicalTrials.gov: NCT02039947 ↗Enrolled (actual)
125
Serious AEs
35.2%
Results posted
May 2019
Primary outcome: Primary: Intracranial Response (IR) Rate in Cohort A — 45 Number of participants — p=<.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Dabrafenib (Drug); Trametinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Intracranial Response (IR) Rate in Cohort A |
45 | <.0001 sig |
| SECONDARY Intracranial Response Rate of Cohorts B, C and D |
9; 7; 10 | — |
| SECONDARY Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort |
59; 14; 12; 15; 60; 11 | — |
| SECONDARY Extracranial Response Rate (ER) for Each Cohort |
42; 7; 12; 7 | — |
| SECONDARY Overall Response (OR) for Each Cohort |
45; 9; 7; 11 | — |
| SECONDARY Duration of Intracranial, Extracranial and Overall Response for Each Cohort |
6.5; 7.3; 8.3; 4.5; 10.2; NA | — |
| SECONDARY Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment |
5.7; 7.2; 3.7; 5.5 | — |
| SECONDARY Overall Survival (OS) for Each Cohort |
10.8; 24.3; 10.1; 11.5 | — |
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.
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 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.
Data sourced from ClinicalTrials.gov (NCT02039947). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.