A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma
Summary
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.
Timeline
- Start
- 2010-12-23
- Primary completion
- 2011-12-19
- Completion
- 2016-09-16
Outcome
Met primary endpoint
registry GSK2118436 150 mg BID vs DTIC 1000 mg/m^2 in RP; p <0.0001; Hazard Ratio (HR) 0.40 (95% CI 0.26 to 0.60) NCT01227889 ↗
registry Hazard Ratio (HR) 0.35 (95% CI 0.20 to 0.61) NCT01227889 ↗
Publications
- Background Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martin-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin AM, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012 Jul 28;380(9839):358-65. doi: 10.1016/S0140-6736(12)60868-X. Epub 2012 Jun 25.
- 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.
- Latimer NR, Abrams KR, Amonkar MM, Stapelkamp C, Swann RS. Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine. Oncologist. 2015 Jul;20(7):798-805. doi: 10.1634/theoncologist.2014-0429. Epub 2015 Jun 3.
- Grob JJ, Amonkar MM, Martin-Algarra S, Demidov LV, Goodman V, Grotzinger K, Haney P, Kampgen E, Karaszewska B, Mauch C, Miller WH Jr, 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 dacarbazine. Ann Oncol. 2014 Jul;25(7):1428-1436. doi: 10.1093/annonc/mdu154. Epub 2014 Apr 25.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dabrafenib | Small molecule | 150 mg | — |
| Comparator | Dacarbazine | Small molecule | 1000 mg/m2 | Intravenous |