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 : Active, not recruiting
First Posted : September 10, 2012
Results First Posted : September 26, 2018
Last Update Posted : September 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Melanoma||Drug: Dabrafenib Drug: Trametinib Drug: Placebos||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||870 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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|
|Actual Study Start Date :||January 8, 2013|
|Actual Primary Completion Date :||June 30, 2017|
|Estimated Study Completion Date :||November 30, 2030|
Experimental: Dabrafenib and trametinib
Subjects received dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
Each capsule contained 50 mg or 75 mg of free base (present as the mesylate salt)
Other Name: GSK2118436
Each tablet contained 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
Other Name: GSK1120212
Placebo Comparator: Dabrafenib and trametinib placebos
Subjects received matching placebos orally for 12 months
The placebo capsules and tablets contained the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment
- 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.
- Overall Survival [ Time Frame: approximately 3.5 years ]Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo
- Distant Metastasis-free Survival [ Time Frame: approximately 3.5 years ]Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo. In the DMFS analysis, the first occurrence of distant metastasis or death (if it occurred before documented recurrence) was counted as an event.
- Freedom From Relapse [ Time Frame: approximately 3.5 years ]Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo. In the FFR analysis, local or distant recurrence or a new primary melanoma were counted as events, and patients who died of causes other than melanoma or treatment-related toxicity were censored.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01682083
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|