Clinical trial NCT02039947: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Melanoma and Brain Metastases
Keywords: BRAF V600K mutation
Metastatic Melanoma
BRAF V600R mutation
BRAF V600D mutation
BRAF V600E mutation
Brain metastases BRAF inhibitor
Intracranial
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-01-20
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Intracranial Response (IR) Rate in Cohort A
timeFrame: From the start of treatment until disease progression or the start of new anti-cancer therapy
Secondary outcomes:
measure: Intracranial Response Rate of Cohorts B, C and D
timeFrame: Approximately 2 years
measure: Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort
timeFrame: Approximately 2 years
measure: Extracranial Response Rate (ER) for Each Cohort
timeFrame: Approximately 2 years
measure: Overall Response (OR) for Each Cohort
timeFrame: Approximately 2 years
measure: Duration of Intracranial, Extracranial and Overall Response for Each Cohort
timeFrame: From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression
measure: Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment
timeFrame: From the first dose to the earliest date of disease progression or death
measure: Overall Survival (OS) for Each Cohort
timeFrame: From the first dose to death
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Chapel Hill
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: North Sydney
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Greenslopes
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Edmonton
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Boulogne-Billancourt
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille Cedex 5
country: France
facility: Novartis Investigative Site
city: Montpellier cedex 5
country: France
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Paris Cedex 10
country: France
facility: Novartis Investigative Site
city: Pierre-Benite cedex
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Rennes Cedex
country: France
facility: Novartis Investigative Site
city: Toulouse cedex
country: France
facility: Novartis Investigative Site
city: Villejuif cedex
country: France
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: Novartis Investigative Site
state: Bayern
city: Hannover
country: Germany
facility: Novartis Investigative Site
state: Niedersachsen
city: Koeln
country: Germany
facility: Novartis Investigative Site
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Gera
country: Germany
facility: Novartis Investigative Site
state: Thueringen
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Milano
country: Italy
facility: Novartis Investigative Site
state: Lombardia
city: Padova
country: Italy
facility: Novartis Investigative Site
state: Veneto
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Las Palmas De Gran Canaria
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
city: Palma de Mallorca
country: Spain
facility: Novartis Investigative Site
city: Pamplona
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Zaragoza
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
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.
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.