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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.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01682083
First Posted: September 10, 2012
Last Update Posted: August 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis
  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
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 Novartis:

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
Actual Study Start Date: January 8, 2013
Estimated Study Completion Date: March 15, 2023
Primary Completion Date: June 30, 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

  Eligibility

Information from the National Library of Medicine

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

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01682083


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Locations
United States, Alabama
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Birmingham, Alabama, United States, 35243
United States, Arizona
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Tucson, Arizona, United States, 85719
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San Francisco, California, United States, 94115
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San Francisco, California, United States, 94143
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Aurora, Colorado, United States, 80045
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Farmington, Connecticut, United States, 06030
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Fort Myers, Florida, United States, 33916
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Lake Worth, Florida, United States, 33461
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Orlando, Florida, United States, 32806
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Saint Petersburg, Florida, United States, 33705
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Stuart, Florida, United States, 34994
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Tampa, Florida, United States, 33612
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Atlanta, Georgia, United States, 30322
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Atlanta, Georgia, United States, 30341
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Indianapolis, Indiana, United States, 46202
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Baltimore, Maryland, United States, 21237
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Lutherville-Timonium, Maryland, United States, 21093
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Boston, Massachusetts, United States, 02114
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Ann Arbor, Michigan, United States, 48019
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Morristown, New Jersey, United States, 07960
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Winston-Salem, North Carolina, United States, 27157
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Seattle, Washington, United States, 98109
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Bordeaux, France, 33075
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Brest cedex, France, 29609
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Grenoble, France, 38043
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Lille, France, 59037
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Marseille cedex 5, France, 13385
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Montpellier cedex 5, France, 34295
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Nice, France, 06202
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Paris Cedex 10, France, 75475
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Japan
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Gdansk, Poland, 80-215
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Poznan, Poland, 60-693
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Warszawa, Poland, 02-781
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Warszawa, Poland, 04-125
Russian Federation
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Ryazan, Russian Federation, 390011
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St. Petersburg, Russian Federation, 191104
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St. Petersburg, Russian Federation, 197758
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St. Petersburg, Russian Federation
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Volgograd, Russian Federation, 400138
Spain
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Badalona, Spain, 08916
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Barcelona, Spain, 08035
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Barcelona, Spain, 08036
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Cartagena (Murcia), Spain, 30202
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Las Palmas De Gran Canaria, Spain, 35016
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Madrid, Spain, 28034
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Madrid, Spain, 28041
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Madrid, Spain, 28046
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Malaga, Spain, 29010
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Palma de Mallorca, Spain, 07198
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Pamplona, Spain, 31008
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San Sebastian, Spain, 20014
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Santander, Spain, 39008
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Sevilla, Spain, 41014
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Valencia, Spain, 46014
Sweden
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Goteborg, Sweden, SE-413 45
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Lund, Sweden, SE-221 85
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Stockholm, Sweden, SE-171 76
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Uppsala, Sweden, SE-751 85
Switzerland
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Basel, Switzerland, 4031
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Chur, Switzerland, 7000
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Zurich, Switzerland, 8091
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Taichung, Taiwan, 404
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Taipei, Taiwan, 100
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Taoyuan, Taiwan, 333
United Kingdom
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Northwood, Middlesex, United Kingdom, HA6 2RN
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Exeter, United Kingdom, EX2 5DW
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Glasgow, United Kingdom, G12 0YN
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Guildford, United Kingdom, GU2 7XX
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Leeds, United Kingdom, LS9 7TF
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London, United Kingdom, NW3 2QG
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London, United Kingdom, SW3 6JJ
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London, United Kingdom, W1G 6AD
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Manchester, United Kingdom, M20 4BX
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Newcastle upon Tyne, United Kingdom, NE7 7DN
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Norwich, United Kingdom, NR4 7UY
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Preston, United Kingdom, PR2 9HT
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Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Novartis
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01682083     History of Changes
Other Study ID Numbers: 115532
First Submitted: September 6, 2012
First Posted: September 10, 2012
Last Update Posted: August 30, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis:
MEK inhibitor
trametinib
Oncology
adjuvant melanoma
dabrafenib
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
Trametinib
Dabrafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action