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Completed

NCT Number: NCT02039947

Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain

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.

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Key information

Conditions

Melanoma and Brain Metastases Brain Diseases Brain Neoplasms Central Nervous System Diseases Central Nervous System Neoplasms Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nervous System Diseases Nervous System Neoplasms Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, North Sydney, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Dabrafenib

Drug

Dabrafenib will be provided as 50 mg and 75 mg capsules

Trametinib

Drug

Trametinib will be provided as 0.5 mg and 2.0 mg tablets

Primary outcomes

  1. 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

  1. Intracranial Response Rate of Cohorts B, C and D

    Time frame: Approximately 2 years

    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

  2. Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort

    Time frame: Approximately 2 years

    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

  3. Extracranial Response Rate (ER) for Each Cohort

    Time frame: Approximately 2 years

    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

  4. Overall Response (OR) for Each Cohort

    Time frame: Approximately 2 years

    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.

  5. 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

    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

  6. 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

    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

  7. Overall Survival (OS) for Each Cohort

    Time frame: From the first dose to death

    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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2018
First posted
Jan 20, 2014
Registry last updated
May 21, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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