A Study Comparing GSK2118436 to Dacarbazine (DTIC) in Previously Untreated Subjects With BRAF Mutation Positive Advanced (Stage III) or Metastatic (Stage IV) Melanoma

NCT01227889 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 113683
• Study Type: interventional
• Target: 251
• Locations: 12 countries
• Sites: 94

Brief 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.

Conditions

Cancer

Keywords

Metastatic melanoma; melanoma; BRAF mutant; Advanced melanoma

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) as Assessed by the Investigator

  PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 millimeters (mm). For participants who did not progress or die, PFS was censored at the date of last contact. Data are presented as median and 96% confidence interval.

  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

  PFS is defined as the interval of time between the date of randomization and the earlier of the date of disease progression or the date of death due to any cause. Disease progression was based on radiographic or photographic evidence, and assessments were made by an independent radiologist according to RECIST version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5 mm. For participants who did not progress or die, PFS was censored at the date of last contact.

  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 (10)

• Overall Survival

  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

  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

  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

  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

  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)

Study Arms (3)

GSK2118436

EXPERIMENTAL

Subjects in this arm will receive GSK2118436 150 mg twice daily.

Drug: GSK2118436

Dacarbazine (DTIC)

ACTIVE COMPARATOR

Subjects will receive intravenous dacarbazine (DTIC) 1000 mg/m2 every 3 weeks

Drug: Dacarbazine (DTIC)

Crossover

EXPERIMENTAL

Subjects who initially receive DTIC will be allowed to receive GSK2118436 after initial progression.

Drug: GSK2118436

Interventions

GSK2118436 DRUG

150 mg twice daily

Crossover; GSK2118436

Dacarbazine (DTIC) DRUG

Intravenous (IV), 1000 mg/m2 every 3 weeks until initial progression

Dacarbazine (DTIC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (94)

GSK Investigational Site

Birmingham, Alabama, 35243, United States

Location

GSK Investigational Site

Mobile, Alabama, 36608, United States

Location

GSK Investigational Site

La Jolla, California, 92093, United States

Location

GSK Investigational Site

Los Angeles, California, 90095, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Vallejo, California, 94589, United States

Location

GSK Investigational Site

Orlando, Florida, 32806, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

GSK Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Westmead, New South Wales, 2145, Australia

Location

GSK Investigational Site

Southport, Queensland, 4215, Australia

Location

GSK Investigational Site

Adelaide, South Australia, 5000, Australia

Location

GSK Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

GSK Investigational Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

GSK Investigational Site

Kelowna, British Columbia, V1Y 5L3, Canada

Location

GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3T 1E2, Canada

Location

GSK Investigational Site

Bordeaux, 33075, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Marseille, 13385, France

Location

GSK Investigational Site

Nice, 06202, France

Location

GSK Investigational Site

Paris, 75006, France

Location

GSK Investigational Site

Paris, 75877, France

Location

GSK Investigational Site

Reims, 51092, France

Location

GSK Investigational Site

Villejuif, 94805, France

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

Location

GSK Investigational Site

Nuremberg, Bavaria, 90419, Germany

Location

GSK Investigational Site

Regensburg, Bavaria, 93053, Germany

Location

GSK Investigational Site

Kassel, Hesse, 34125, Germany

Location

GSK Investigational Site

Wiesbaden, Hesse, 65191, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30449, Germany

Location

GSK Investigational Site

Bonn, North Rhine-Westphalia, 53127, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Koblenz, Rhineland-Palatinate, 56068, Germany

Location

GSK Investigational Site

Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Homburg, Saarland, 66421, Germany

Location

GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

GSK Investigational Site

Kiel, Schleswig-Holstein, 24105, Germany

Location

GSK Investigational Site

Erfurt, Thuringia, 99089, Germany

Location

GSK Investigational Site

Gera, Thuringia, 07548, Germany

Location

GSK Investigational Site

Jena, Thuringia, 07740, Germany

Location

GSK Investigational Site

Budapest, H-1122, Hungary

Location

GSK Investigational Site

Debrecen, 4032, Hungary

Location

GSK Investigational Site

Győr, H-9024, Hungary

Location

GSK Investigational Site

Miskolc, 3526, Hungary

Location

GSK Investigational Site

Pécs, 7624, Hungary

Location

GSK Investigational Site

Cork, Ireland

Location

GSK Investigational Site

Dublin, 4, Ireland

Location

GSK Investigational Site

Dublin, 7, Ireland

Location

GSK Investigational Site

Dublin, 8, Ireland

Location

GSK Investigational Site

Dublin, 9, Ireland

Location

GSK Investigational Site

Galway, Co Galway, Ireland

Location

GSK Investigational Site

Modena, Emilia-Romagna, 41100, Italy

Location

GSK Investigational Site

Udine, Friuli Venezia Giulia, 33100, Italy

Location

GSK Investigational Site

Rome, Lazio, 00144, Italy

Location

GSK Investigational Site

Rome, Lazio, 00167, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Rozzano (MI), Lombardy, 20089, Italy

Location

GSK Investigational Site

Siena, Tuscany, 53100, Italy

Location

GSK Investigational Site

Terni, Umbria, 05100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35128, Italy

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Brzozów, 36-200, Poland

Location

GSK Investigational Site

Konin, 62-500, Poland

Location

GSK Investigational Site

Krakow, 31-115, Poland

Location

GSK Investigational Site

Słupsk, 76-200, Poland

Location

GSK Investigational Site

Warsaw, 02-781, Poland

Location

GSK Investigational Site

Kazan', 420029, Russia

Location

GSK Investigational Site

Moscow, 115478, Russia

Location

GSK Investigational Site

Ryazan, 390011, Russia

Location

GSK Investigational Site

Saint Petersburg, 191104, Russia

Location

GSK Investigational Site

Saint Petersburg, 197758, Russia

Location

GSK Investigational Site

Saint Petersburg, 198255, Russia

Location

GSK Investigational Site

Stavropol, 355047, Russia

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28033, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28050, Spain

Location

GSK Investigational Site

Pamplona, 31008, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

Related Publications (6)

• 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.

  PMID: 22735384 BACKGROUND

• 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.

  PMID: 31864178 DERIVED

• 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.

  PMID: 26446943 DERIVED

• 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.

  PMID: 26040620 DERIVED

• 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.

  PMID: 24769640 DERIVED

• 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.

  PMID: 24408395 DERIVED

MeSH Terms

Conditions

Neoplasms; Melanoma

Interventions

dabrafenib; Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: October 25, 2010
• Study Start: December 23, 2010
• Primary Completion: December 19, 2011
• Study Completion: September 16, 2016
• Last Updated: October 4, 2017
• Results First Posted: May 16, 2014

Record last verified: 2017-08

Locations

RU (7); IE (6); DE (21); US (11); CA (5); HU (5); FR (8); AU (4); IT (9); ES (12); PL (5); NL (1)