A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. - Full Text View

Purpose

This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma will be screened for eligibility. Subjects will be randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.

Condition	Intervention	Phase
Melanoma	Drug: Dabrafenib Drug: Trametinib Drug: Placebos	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

U.S. FDA Resources

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:

Relapse-free survival (RFS) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
Safety of dabrafenib and trametinib as a combination therapy in the overall study population [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	852
Study Start Date:	January 2013
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dabrafenib and trametinib combination therapy Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.	Drug: Dabrafenib Each capsule contains 50 mg or 75 mg of free base (present as the mesylate salt) Drug: Trametinib Each tablet contains 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
Placebo Comparator: Dabrafenib and trametinib placebos Subjects will receive matching placebos orally for 12 months	Drug: Placebos The placebo capsules and tablets contain the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

Eligibility

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

Criteria

Inclusion Criteria:

Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis &gt;1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory.
Surgically rendered free of disease no more than 12 weeks before randomization.
Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Adequate hematologic, hepatic, renal and cardiac function.

Exclusion Criteria:

Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
Evidence of distant metastatic disease.
Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease free for > 5 years.
History or current evidence of cardiovascular risk.
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01682083

Contacts

Contact: US GSK Clinical Trials Call Center

877-379-3718

GSKClinicalSupportHD@gsk.com

Show 138 Study Locations

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

GlaxoSmithKline

More Information

No publications provided

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01682083 History of Changes
Other Study ID Numbers:	115532
Study First Received:	September 6, 2012
Last Updated:	February 7, 2013
Health Authority:	Unspecified

Keywords provided by GlaxoSmithKline:

MEK inhibitor
Oncology
adjuvant melanoma

dabrafenib and trametinib combination therapy
BRAF mutation-positive melanoma
BRAF inhibitor

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
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013

A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. (COMBI-AD)