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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01153763




Registration number
NCT01153763
Ethics application status
Date submitted
27/05/2010
Date registered
30/06/2010
Date last updated
27/09/2017

Titles & IDs
Public title
A Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
Scientific title
A Phase II (BRF113710) Single-arm, Open-label Study of GSK2118436 in BRAF Mutant Metastatic Melanoma
Secondary ID [1] 0 0
113710
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK2118436

Other: All patients - Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.


Treatment: Drugs: GSK2118436
Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [1] 0 0
Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Timepoint [1] 0 0
Up to 60 months
Secondary outcome [2] 0 0
Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
Timepoint [2] 0 0
Up to 60 months
Secondary outcome [3] 0 0
Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Timepoint [3] 0 0
Up to 60 months
Secondary outcome [4] 0 0
Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation
Timepoint [4] 0 0
Up to 60 months
Secondary outcome [5] 0 0
Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation
Timepoint [5] 0 0
Up to 60 months
Secondary outcome [6] 0 0
Overall Survival for Participants Who Had a BRAF V600E Mutation
Timepoint [6] 0 0
Up to 60 months
Secondary outcome [7] 0 0
Overall Survival for Participants Who Had a BRAF V600K Mutation
Timepoint [7] 0 0
From the first dose to death due to any cause (up to 60 months)
Secondary outcome [8] 0 0
Number of Participants With AEs and Serious Adverse Events (SAEs)
Timepoint [8] 0 0
Up to 60 months
Secondary outcome [9] 0 0
Number of Participants With Change From Baseline in Clinical Chemistry and Hematology Toxicity Grades
Timepoint [9] 0 0
Up to 60 months
Secondary outcome [10] 0 0
Number of Participants With Change From Baseline in Temperature and Pulse Rate
Timepoint [10] 0 0
Up to 60 months
Secondary outcome [11] 0 0
Number of Participants With Increase From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Timepoint [11] 0 0
Up to 60 months
Secondary outcome [12] 0 0
Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels
Timepoint [12] 0 0
Up to 60 months

Eligibility
Key inclusion criteria
* Must be at least 18 years of age
* Must have histologically confirmed cutaneous metastatic melanoma (Stage IV) that is BRAF mutation-positive (V600 E/K) as determined via central testing with a BRAF mutation assay.
* Is treatment naive or has received prior treatment for metastatic melanoma.
* Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
* Women of child-bearing potential must have a negative pregnancy test within 14 days prior to the first dose of study treatment.
* Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 4 weeks after the last dose of study medication.
* Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 16 weeks after the last dose of study medication.
* Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
* Adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with a BRAF or MEK inhibitor.
* Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436.
* A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection.
* History or evidence of brain metastases on MRI or head CT if MRI is not able to be performed.
* History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
* Certain cardiac abnormalities.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
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
9/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2016
Sample size
Target
Accrual to date
Final
92
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Newcastle
Recruitment hospital [2] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [3] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2300 - Newcastle
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
France
State/province [5] 0 0
Bordeaux
Country [6] 0 0
France
State/province [6] 0 0
Boulogne-Billancourt
Country [7] 0 0
France
State/province [7] 0 0
Lille
Country [8] 0 0
France
State/province [8] 0 0
Marseille Cedex 5
Country [9] 0 0
France
State/province [9] 0 0
Montpellier
Country [10] 0 0
France
State/province [10] 0 0
Paris Cedex 10
Country [11] 0 0
France
State/province [11] 0 0
Villejuif
Country [12] 0 0
Germany
State/province [12] 0 0
Nordrhein-Westfalen
Country [13] 0 0
Germany
State/province [13] 0 0
Schleswig-Holstein
Country [14] 0 0
Germany
State/province [14] 0 0
Berlin
Country [15] 0 0
Italy
State/province [15] 0 0
Campania
Country [16] 0 0
Italy
State/province [16] 0 0
Liguria
Country [17] 0 0
Italy
State/province [17] 0 0
Veneto

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

Ethics approval
Ethics application status

Summary
Brief summary
BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.
Trial website
https://clinicaltrials.gov/study/NCT01153763
Trial related presentations / publications
Ascierto PA, Minor D, Ribas A, Lebbe C, O'Hagan A, Arya N, Guckert M, Schadendorf D, Kefford RF, Grob JJ, Hamid O, Amaravadi R, Simeone E, Wilhelm T, Kim KB, Long GV, Martin AM, Mazumdar J, Goodman VL, Trefzer U. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013 Sep 10;31(26):3205-11. doi: 10.1200/JCO.2013.49.8691. Epub 2013 Aug 5.
Hauschild A, Ascierto PA, Schadendorf D, Grob JJ, Ribas A, Kiecker F, Dutriaux C, Demidov LV, Lebbe C, Rutkowski P, Blank CU, Gutzmer R, Millward M, Kefford R, Haas T, D'Amelio A Jr, Gasal E, Mookerjee B, Chapman PB. Long-term outcomes in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib monotherapy: Analysis from phase 2 and 3 clinical trials. Eur J Cancer. 2020 Jan;125:114-120. doi: 10.1016/j.ejca.2019.10.033.
Santiago-Walker A, Gagnon R, Mazumdar J, Casey M, Long GV, Schadendorf D, Flaherty K, Kefford R, Hauschild A, Hwu P, Haney P, O'Hagan A, Carver J, Goodman V, Legos J, Martin AM. Correlation of BRAF Mutation Status in Circulating-Free DNA and Tumor and Association with Clinical Outcome across Four BRAFi and MEKi Clinical Trials. Clin Cancer Res. 2016 Feb 1;22(3):567-74. doi: 10.1158/1078-0432.CCR-15-0321. Epub 2015 Oct 7.
Ouellet D, Gibiansky E, Leonowens C, O'Hagan A, Haney P, Switzky J, Goodman VL. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014 Jun;54(6):696-706. doi: 10.1002/jcph.263. Epub 2014 Jan 17.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
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/NCT01153763