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

GSK study ID
113683
See study documents
Clinicaltrials.gov ID
NCT01227889
See results summary
EudraCT ID
2009-015298-11
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

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:
  • Drug: GSK2118436
  • Drug: Dacarbazine (DTIC)
    • 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
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    St. Petersburg, Russia, 197758
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Roma, Lazio, Italy, 00167
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Toronto, Ontario, Canada, M4N 3M5
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Kassel, Hessen, Germany, 34125
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Southport, Queensland, Australia, 4215
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Debrecen, Hungary, 4032
    Status
    Study Complete
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    Showing 1 - 6 of 94 Results

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)

    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
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