Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD). (COMBI-AD)
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ClinicalTrials.gov Identifier: NCT01682083 |
Recruitment Status :
Completed
First Posted : September 10, 2012
Results First Posted : September 26, 2018
Last Update Posted : August 30, 2023
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Tracking Information | |||||
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First Submitted Date ICMJE | September 6, 2012 | ||||
First Posted Date ICMJE | September 10, 2012 | ||||
Results First Submitted Date ICMJE | May 29, 2018 | ||||
Results First Posted Date ICMJE | September 26, 2018 | ||||
Last Update Posted Date | August 30, 2023 | ||||
Actual Study Start Date ICMJE | January 8, 2013 | ||||
Actual Primary Completion Date | June 30, 2017 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Relapse-free Survival (RFS) [ Time Frame: Approximately 3.5 years ] Recurrence-free survival was defined as the time from randomization to disease recurrence (local recurrence, distant recurrence, second primary melanoma), or death from any cause.
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Original Primary Outcome Measures ICMJE |
Relapse-free survival (RFS) in subjects [ Time Frame: From date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed for an average of 24 months ] The efficacy of dabrafenib and trametinib combination therapy compared to placebo was evaluated by measuring RFS. Relapse Free Survival is defined as the time from randomization to disease recurrence or death from any cause. Recurrence of or death from the same cancer and all deaths from other causes are events. Treatment emergent malignancy(ies) other than second melanomas will not be considered as events, and loss to follow-up is censored. Subjects without RFS events will be censored at the last assessment
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Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | Dabrafenib With Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma (COMBI-AD). | ||||
Official Title ICMJE | 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 | ||||
Brief Summary | This was 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 were screened for eligibility. Subjects were 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. | ||||
Detailed Description | This was a two-arm, randomized, double-blind, multi-center, international phase III study of dabrafenib in combination with trametinib versus two matching 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 were screened for eligibility. Subjects were randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]). None of the patients had undergone previous systemic anticancer treatment or radiotherapy for melanoma. All the patients had undergone completion lymphadenectomy with no clinical or radiographic evidence of residual regional node disease within 12 weeks before randomization, had recovered from definitive surgery, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. BRAF V600 mutation status was confirmed in primary-tumor or lymph-node tissue by a central reference laboratory. All the patients provided written informed consent. The primary end point was recurrence-free survival, Overall survival, as the key secondary end point, was to be tested in a hierarchical manner only if the primary end point met the criteria for significance. The overall survival analysis used a preplanned three-look Lan-DeMets group sequential design with an O'Brien-Fleming-type boundary, which was used to determine the significance threshold for the first interim overall survival analysis (two-sided P=0.000019). Disease assessments included clinical examination and imaging by means of computed tomography, magnetic resonance imaging, or both.) Imaging was performed every 3 months during the first 24 months, then every 6 months until disease recurrence or the completion of the trial. Follow-up for survival began after recurrence and continued through the end of the trial. Adverse events and laboratory values were assessed at screening, on the date of randomization, at least once per month through month 12, and at every visit for disease-recurrence assessment after month 12. Adverse events and laboratory values were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Melanoma | ||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Actual Enrollment ICMJE |
870 | ||||
Original Estimated Enrollment ICMJE |
1300 | ||||
Actual Study Completion Date ICMJE | July 31, 2023 | ||||
Actual Primary Completion Date | June 30, 2017 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Key Inclusion Criteria:
Key Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Listed Location Countries ICMJE | Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States | ||||
Removed Location Countries | Czech Republic, Finland | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT01682083 | ||||
Other Study ID Numbers ICMJE | 115532 2012-001266-15 ( EudraCT Number ) CDRB436F2301 ( Other Identifier: Novartis ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | Novartis ( Novartis Pharmaceuticals ) | ||||
Original Responsible Party | GlaxoSmithKline | ||||
Current Study Sponsor ICMJE | Novartis Pharmaceuticals | ||||
Original Study Sponsor ICMJE | GlaxoSmithKline | ||||
Collaborators ICMJE | Not Provided | ||||
Investigators ICMJE |
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PRS Account | Novartis | ||||
Verification Date | August 2023 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |