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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Cancer

Treatments: Drug: Dacarbazine (DTIC); Drug: GSK2118436

Study type: Interventional

Funder types: Industry

Identifiers

NCT01227889

113683

Details and patient eligibility

About

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.

Enrollment: 251 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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251 participants in 3 patient groups

GSK2118436

Experimental group

Description:

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

Treatment:

Drug: GSK2118436

Dacarbazine (DTIC)

Active Comparator group

Description:

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

Treatment:

Drug: Dacarbazine (DTIC)

Crossover

Experimental group

Description:

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

Treatment:

Drug: GSK2118436