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Trial record 1 of 1 for:    NCT01682083
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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)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: September 6, 2012
Last updated: May 1, 2017
Last verified: May 2017
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
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Relapse-free survival (RFS) [ Time Frame: Approximately 32 months ]

Secondary Outcome Measures:
  • Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 5 years ]
  • Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ]
  • Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ]
  • Safety of dabrafenib and trametinib as a combination therapy in the overall study population [ Time Frame: approximately 5 years ]

Estimated Enrollment: 852
Study Start Date: January 8, 2013
Estimated Study Completion Date: December 1, 2017
Estimated Primary Completion Date: December 1, 2017 (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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  • 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
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Please refer to this study by its identifier: NCT01682083

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Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Responsible Party: GlaxoSmithKline Identifier: NCT01682083     History of Changes
Other Study ID Numbers: 115532
Study First Received: September 6, 2012
Last Updated: May 1, 2017

Keywords provided by GlaxoSmithKline:
MEK inhibitor
adjuvant melanoma
dabrafenib and trametinib combination therapy
BRAF mutation-positive melanoma
BRAF inhibitor

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on August 22, 2017