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

Sponsor:	GlaxoSmithKline
Information provided by (Responsible Party):	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01227889

Purpose

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.

Condition	Intervention	Phase
Cancer	Drug: GSK2118436 Drug: Dacarbazine (DTIC)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: Help Me Understand Genetics

MedlinePlus related topics: Cancer Melanoma

Drug Information available for: Dacarbazine

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Progression free survival (PFS), defined as the time from randomization until the first date of either objective disease progression or death due to any cause. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (OS) defined as the time from randomization to death due to any cause [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
PFS, defined for subjects randomized to the DTIC treatment groups as the time to progression or death after cross-over to GSK2118436 after initial progression on DTIC. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Overall response rate (ORR), defined as the percentage of subjects achieving either a commplete or partial tumor response. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Duration of response, defined for those subjects who show a complete or partial tumor response, the time from first documented complete response or partial response until the first documented sign of disease progression or death due to any cause. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Duration of response in subjects who cross-over to GSK2118436, after initial progression on DTIC [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Rate of treatment-emergent non-melanoma skin lesions in each treatment group, defined as the percentage of subjects with non-melanoma skin lesions reported [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
Validation of the BRAF mutation assay. [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]

Enrollment:	250
Study Start Date:	January 2011
Estimated Study Completion Date:	June 2012
Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GSK2118436 Subjects in this arm will receive GSK2118436 150 mg twice daily.	Drug: GSK2118436 150 mg twice daily
Active Comparator: Dacarbazine (DTIC) Subjects will receive intravenous dacarbazine (DTIC) 1000 mg/m2 every 3 weeks	Drug: Dacarbazine (DTIC) Intravenous (IV), 1000 mg/m2 every 3 weeks until initial progression
Experimental: Crossover Subjects who initially receive DTIC will be allowed to receive GSK2118436 after initial progression.	Drug: GSK2118436 150 mg twice daily

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01227889

Show 88 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01227889 History of Changes
Other Study ID Numbers:	113683
Study First Received:	October 21, 2010
Last Updated:	May 17, 2012
Health Authority:	Italy: AIFA - Italian Ministry of Health France: Ministry of Health Italy: Comitato Etico Fondazione Centro San Raffaele del Monte Tabor - Via Olgettina, 60 - 20132 Milano Canada: Health Canada Hungary: National Institute of Pharmacy Spain: Ministry of Health and Consumption Ireland: Irish Medicines Board United States: Food and Drug Administration Russia: Russian Ministry of Health Poland: Ministry of Health Germany: Bundesinstitut für Arzneimittel und Medizinprodukte Netherlands: Medical Ethics Review Committee (METC) Australia: Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:

Metastatic melanoma
melanoma
BRAF mutant
Advanced melanoma

Additional relevant MeSH terms:

Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2012