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.
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
- ORG STUDY ID:
117277
- NCT ID:
NCT02039947
Conditions
- Melanoma and Brain Metastases
Interventions
| Drug | Synonyms | Arms |
|---|
| Dabrafenib | | Cohort A |
| Trametinib | | Cohort A |
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.
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. | |
| 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 | |
| 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 | |
| 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 | |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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 |
| Safety Issue: | |
| Description: | 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 Outcome Measures
| Measure: | Intracranial Response Rate of Cohorts B, C and D |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | 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. No hypothesis testing completed for cohort A, B,C and D |
| Measure: | Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Disease Control rate is defined as the percentage of subjects achieving a confirmed intracranial/extracranial/overall CR or PR or SD or Non-CR/Non-PD. This is based on investigator-assessed response. No hypothesis testing completed for cohort A, B,C and D |
| Measure: | Extracranial Response Rate (ER) for Each Cohort |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Extracranial Response Rate was defined as the percentage of participants with Complete response (CR) or Partial response (PR) at anytime. This is based on investigator-assessed response. No hypothesis testing completed for cohort A,B,C and D |
| Measure: | Overall Response (OR) for Each Cohort |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | the number of subjects with a confirmed overall Complete response (CR) or Partial response (PR) by investigator assessment using the Response evaluation criteria in solid tumors (RECIST 1.1 criteria). To determine the overall response, all target and non-target lesions will be assessed using modified RECIST 1.1 criteria. |
| Measure: | Duration of Intracranial, Extracranial and Overall Response for Each Cohort |
| Time Frame: | From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression |
| Safety Issue: | |
| Description: | Duration of intracranial, extracranial and overall response, are defined as the time from first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression. No hypothesis testing completed for cohort A,B,C and D |
| Measure: | Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment |
| Time Frame: | From the first dose to the earliest date of disease progression or death |
| Safety Issue: | |
| Description: | PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. No hypothesis testing completed for cohort A,B,C and D |
| Measure: | Overall Survival (OS) for Each Cohort |
| Time Frame: | From the first dose to death |
| Safety Issue: | |
| Description: | Overall survival (OS) is defined as the time from the first dose until death due to any cause. No hypothesis testing completed for cohort A,B,C and D |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- BRAF V600K mutation
- Metastatic Melanoma
- BRAF V600R mutation
- BRAF V600D mutation
- BRAF V600E mutation
- Brain metastases BRAF inhibitor
- Intracranial
Last Updated
May 21, 2019
