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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02039947




Registration number
NCT02039947
Ethics application status
Date submitted
19/12/2013
Date registered
20/01/2014
Date last updated
21/05/2019

Titles & IDs
Public title
Study to Evaluate Treatment of Dabrafenib Plus Trametinib in Subjects With BRAF Mutation-Positive Melanoma That Has Metastasized to the Brain
Scientific 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
Secondary ID [1] 0 0
117277
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma and Brain Metastases 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dabrafenib
Treatment: Drugs - Trametinib

Experimental: Cohort A - Subjects will receive dabrafenib 150 milligram (mg) twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity.

Experimental: Cohort B - Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

Experimental: Cohort C - Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity

Experimental: Cohort D - Subjects will receive dabrafenib 150 mg twice daily and trametinib 2 mg once daily until evidence of disease progression, death, or unacceptable toxicity


Treatment: Drugs: Dabrafenib
Dabrafenib will be provided as 50 mg and 75 mg capsules

Treatment: Drugs: Trametinib
Trametinib will be provided as 0.5 mg and 2.0 mg tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Intracranial Response (IR) Rate in Cohort A
Timepoint [1] 0 0
From the start of treatment until disease progression or the start of new anti-cancer therapy
Secondary outcome [1] 0 0
Intracranial Response Rate of Cohorts B, C and D
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [2] 0 0
Disease Control for Intracranial, Extracranial and Overall Response for Each Cohort
Timepoint [2] 0 0
Approximately 2 years
Secondary outcome [3] 0 0
Extracranial Response Rate (ER) for Each Cohort
Timepoint [3] 0 0
Approximately 2 years
Secondary outcome [4] 0 0
Overall Response (OR) for Each Cohort
Timepoint [4] 0 0
Approximately 2 years
Secondary outcome [5] 0 0
Duration of Intracranial, Extracranial and Overall Response for Each Cohort
Timepoint [5] 0 0
From first documented evidence of CR or PR until time of first documented intracranial, extracranial, or overall disease progression
Secondary outcome [6] 0 0
Progression-free Survival (PFS) for Each Cohort Based on Investigator Assessment
Timepoint [6] 0 0
From the first dose to the earliest date of disease progression or death
Secondary outcome [7] 0 0
Overall Survival (OS) for Each Cohort
Timepoint [7] 0 0
From the first dose to death

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/02/2018
Sample size
Target
Accrual to date
Final
127
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [2] 0 0
Novartis Investigative Site - Greenslopes
Recruitment hospital [3] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2060 - North Sydney
Recruitment postcode(s) [2] 0 0
4120 - Greenslopes
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
France
State/province [14] 0 0
Boulogne-Billancourt
Country [15] 0 0
France
State/province [15] 0 0
Lille
Country [16] 0 0
France
State/province [16] 0 0
Marseille Cedex 5
Country [17] 0 0
France
State/province [17] 0 0
Montpellier cedex 5
Country [18] 0 0
France
State/province [18] 0 0
Nantes Cedex 1
Country [19] 0 0
France
State/province [19] 0 0
Paris Cedex 10
Country [20] 0 0
France
State/province [20] 0 0
Pierre-Benite cedex
Country [21] 0 0
France
State/province [21] 0 0
Poitiers
Country [22] 0 0
France
State/province [22] 0 0
Rennes Cedex
Country [23] 0 0
France
State/province [23] 0 0
Toulouse cedex
Country [24] 0 0
France
State/province [24] 0 0
Villejuif cedex
Country [25] 0 0
Germany
State/province [25] 0 0
Baden-Wuerttemberg
Country [26] 0 0
Germany
State/province [26] 0 0
Bayern
Country [27] 0 0
Germany
State/province [27] 0 0
Niedersachsen
Country [28] 0 0
Germany
State/province [28] 0 0
Nordrhein-Westfalen
Country [29] 0 0
Germany
State/province [29] 0 0
Schleswig-Holstein
Country [30] 0 0
Germany
State/province [30] 0 0
Thueringen
Country [31] 0 0
Italy
State/province [31] 0 0
Lombardia
Country [32] 0 0
Italy
State/province [32] 0 0
Veneto
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Las Palmas De Gran Canaria
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Spain
State/province [36] 0 0
Malaga
Country [37] 0 0
Spain
State/province [37] 0 0
Palma de Mallorca
Country [38] 0 0
Spain
State/province [38] 0 0
Pamplona
Country [39] 0 0
Spain
State/province [39] 0 0
Valencia
Country [40] 0 0
Spain
State/province [40] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02039947
Trial related presentations / publications
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02039947