TriangleNCT02039947 · CITED IN SOURCE DOCUMENTS
Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2019-05-21
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Intracranial Response (IR) Rate in Cohort A
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 Based on Investigator Assessment
Overall Survival (OS) for Each Cohort
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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 Names
- Drug: Dabrafenib
- Drug: Trametinib
- label
- Cohort A
- type
- EXPERIMENTAL
- description
- Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
- intervention Names
- Drug: Dabrafenib
- Drug: Trametinib
- label
- Cohort B
- type
- EXPERIMENTAL
- description
- Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
- intervention Names
- Drug: Dabrafenib
- Drug: Trametinib
- label
- Cohort C
- type
- EXPERIMENTAL
- description
- Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity
- intervention Names
- Drug: Dabrafenib
- Drug: Trametinib
- label
- Cohort D
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort A
- Cohort B
- Cohort C
- Cohort D
- description
- Dabrafenib will be provided as 50 mg and 75 mg capsules
- name
- Dabrafenib
- type
- DRUG
- arm Group Labels
- Cohort A
- Cohort B
- Cohort C
- Cohort D
- description
- Trametinib will be provided as 0.5 mg and 2.0 mg tablets
- name
- Trametinib
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 127
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- 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.
- 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
- secondary Outcomes
- 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
- Intracranial Response Rate of Cohorts B, C and D
- time Frame
- Approximately 2 years
- 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
- Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort
- time Frame
- Approximately 2 years
- 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
- Extracranial Response Rate (ER) for Each Cohort
- time Frame
- Approximately 2 years
- 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
- Overall Response (OR) for Each Cohort
- time Frame
- Approximately 2 years
- 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
- 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
- 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
- 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
- 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
- measure
- Overall Survival (OS) for Each Cohort
- time Frame
- From the first dose to death
Full study description
- 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.
Source references
- references
- citation
- Syeda MM, Wiggins JM, Corless BC, Long GV, Flaherty KT, Schadendorf D, Nathan PD, Robert C, Ribas A, Davies MA, Grob JJ, Gasal E, Squires M, Marker M, Garrett J, Brase JC, Polsky D. Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or dabrafenib plus trametinib: a clinical validation study. Lancet Oncol. 2021 Mar;22(3):370-380. doi: 10.1016/S1470-2045(20)30726-9. Epub 2021 Feb 12.
- pmid
- 33587894
- type
- DERIVED
- citation
- Davies MA, Saiag P, Robert C, Grob JJ, Flaherty KT, Arance A, Chiarion-Sileni V, Thomas L, Lesimple T, Mortier L, Moschos SJ, Hogg D, Marquez-Rodas I, Del Vecchio M, Lebbe C, Meyer N, Zhang Y, Huang Y, Mookerjee B, Long GV. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):863-873. doi: 10.1016/S1470-2045(17)30429-1. Epub 2017 Jun 4.
- pmid
- 28592387
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice