Last updated: 11/03/2018 15:31:13
A study comparing GSK2118436 to Dacarbazine (DTIC) in previously untreated subjects with BRAF mutation positive advanced (Stage III) or metastatic (Stage IV) melanoma
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A Phase III randomized, open-label study comparing GSK2118436 to Dacarbazine (DTIC) in previously untreated subjects with BRAF mutation positive advanced (Stage III) or metastatic (Stage IV) melanoma
Trial description: BRF113683 is a Phase III, randomized, open-label study comparing the efficacy, safety, and tolerability of GSK2118436 to dacarbazine (DTIC), in subjects with BRAF mutant advanced (Stage III) or metastatic (Stage IV) melanoma. Subjects will be randomized to receive 150 mg of GSK2118436 twice daily or 1000 mg/m2 DTIC every 3 weeks and continue on treatment until disease progression, death, or unacceptable adverse event. Subjects who progress on DTIC will be allowed to crossover to an optional extension arm of the study to receive GSK2118436.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Progression-free Survival (PFS) as assessed by the Investigator
Timeframe: Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
Progression-free Survival (PFS) as assessed by an Independent Radiologist: Randomized Phase
Timeframe: Time interval between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause (up to 9.9 months)
Secondary outcomes:
Overall survival
Timeframe: Time interval between the date of randomization and the date of death due to any cause (up to 22.1 months)
Number of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator: Randomized Phase
Timeframe: From randomization until the first documented evidence of a confirmed complete response or partial response (median of 6.6 weeks)
Number of participants with a best overall response of confirmed CR or PR as assessed by an Independent Radiologist: Randomized Phase
Timeframe: From randomization until the first documented evidence of a confirmed complete response or partial response (median of 12.0 weeks)
Duration of Response as assessed by the Investigator: Randomized Phase
Timeframe: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 65.6 weeks)
Duration of Response as assessed by an Independent Radiologist: Randomized Phase
Timeframe: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 7.4 months)
Progression-free Survival (PFS2) as assessed by the Investigator: Crossover Phase
Timeframe: Time from first dose of GSK2118436 in participants who crossover after initial progression to the earliest date of radiographical or photographical PD or death due to any cause (up to 6.4 months)
Number of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by the Investigator: Crossover Phase
Timeframe: From randomization until the first documented evidence of a confirmed complete response or partial response (up to 6.4 months)
Duration of Response as assessed by the Investigator: Crossover Phase
Timeframe: Time from the first documented evidence of PR or CR until the first documented sign of disease progression or death due to any cause (up to 6.4 months)
Number of participants with non-melanoma skin lesions: Randomized Phase
Timeframe: From Screening until study completion or discontinuation from the study (up to 9.9 months)
Agreement rate for V600E mutation validation of the BRAF mutation assay
Timeframe: Screening
Interventions:
Enrollment:
251
Primary completion date:
2011-19-12
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
A Hauschild, JJ Grob, LV Demidov, T Jouary, R Gutzmer, M Millward, P Rutkowski, CU Blank, WH Miller, E Kaempgen, S Martin-Algarra, B Karaszewska, C Mauch, V Chiarion-Sileni, AM Martin, S Swann, P Haney, B Mirakhur, ME Guckert, V Goodman, PB Chapman. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. [Lancet]. 2012;380(9839):358-365.
A Hauschild, JJ Grob, LV Demidov, T Jouary, R Gutzmer, M Millward, P Rutkowski, CU Blank, WH Miller, E Kaempgen, S Martin-Algarra, B Karaszewska, C Mauch, V Chiarion-Sileni, AM Martin, S Swann, P Haney, B Mirakhur, ME Guckert, V Goodman, PB Chapman. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358-365.
Daniele Ouellet, Ekaterina Gibiansky, Cathrine L Denton, Anne O’Hagan, Pat Haney, Julie Switzky, Vicki Goodman. Population Pharmacokinetics of Dabrafenib: Effect of Dose, Time, Covariates and Relationship with its Metabolites . J Clin Pharmacol. 2014;54(6):696-706.
Grob J-J, Amonkar MM, Martin-Algarra S, Demidov LV, Goodman VL, Grotzinger K, Haney P, Kaempgen E, Karaszewska B, Mauch C, Miller Jr. WH, Millward M, Mirakhur B, Rutkowski P, Chiarion-Sileni V, Swann S, Hauschild A. Patient perception of the benefit of a BRAF inhibitor in metastatic melanoma: Quality of life analyses of the BREAK-3 study comparing dabrafenib with DTIC. Ann Oncol. 2014;25(7):1428-36.
Medical condition
Cancer
Product
dabrafenib
Collaborators
Not applicable
Study date(s)
December 2010 to September 2016
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Adults at least 18 years of age
- Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E)
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
- Evidence of active central nervous system (CNS) disease.
Inclusion and exclusion criteria
Inclusion criteria:
- Adults at least 18 years of age
- Has advanced (unresectable Stage III) or metastatic (Stage IV) melanoma that is BRAF mutation positive (V600E)
- Is treatment naive for advanced (unresectable) or metastatic melanoma, with the exception of Interleukin 2 (IL-2) which is allowed.
- Has measurable disease according to RECIST 1.1 criteria.
- 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 adequate organ function.
- Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Exclusion criteria:
- Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy or surgery).
- Evidence of active central nervous system (CNS) disease.
- Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor.
- A history of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of complete resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
- History of Human Immunodeficiency Virus (HIV) infection.
- Certain cardiac abnormalities
Trial location(s)
Location
GSK Investigational Site
Southport, Queensland, Australia, 4215
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35243
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30449
Status
Study Complete
Location
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Status
Study Complete
Location
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
Status
Study Complete
Location
GSK Investigational Site
Kelowna, British Columbia, Canada, V1Y 5L3
Status
Study Complete
Location
GSK Investigational Site
Hospitalet de Llobregat, Barcelona, Spain, 08907
Status
Study Complete
Location
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Status
Study Complete
Location
GSK Investigational Site
Adelaide, South Australia, Australia, 5000
Status
Study Complete
Location
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39120
Status
Study Complete
Location
GSK Investigational Site
Koblenz, Rheinland-Pfalz, Germany, 56068
Status
Study Complete
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24105
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32806
Status
Study Complete
Location
GSK Investigational Site
Vallejo, California, United States, 94589
Status
Study Complete
Location
GSK Investigational Site
San Francisco, California, United States, 94115
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53127
Status
Study Complete
Location
GSK Investigational Site
Rozzano (MI), Lombardia, Italy, 20089
Status
Terminated/Withdrawn
Location
GSK Investigational Site
La Jolla, California, United States, 92093
Status
Study Complete
Location
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
Status
Study Complete
Location
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
Status
Study Complete
Location
GSK Investigational Site
Los Angeles, California, United States, 90095
Status
Study Complete
Location
GSK Investigational Site
Udine, Friuli-Venezia-Giulia, Italy, 33100
Status
Study Complete
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
Ludwigshafen, Rheinland-Pfalz, Germany, 67063
Status
Study Complete
Location
GSK Investigational Site
Westmead, New South Wales, Australia, 2145
Status
Study Complete
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
Status
Study Complete
Location
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2011-19-12
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
Participate in clinical trial
Access to clinical trial data by researchers
Visit website