NCT03551626

Study of Dabrafenib+Trametinib in the Adjuvant Treatment of Stage III BRAF V600+ Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes

COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 552 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The main purpose of this study was to evaluate the impact on pyrexia-related outcomes of an adapted pyrexia adverse event (AE)-management algorithm, as well as safety, efficacy and health-related outcomes.

Detailed description

This was an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk cutaneous melanoma were screened for eligibility. This study consisted of two periods: 1. Treatment Period - patients received up to 12 months of dabrafenib (150 mg twice daily) and trametinib (2 mg once daily). In the adapted pyrexia management algorithm, dabrafenib and trametinib were interrupted promptly at the onset of pyrexia (≥38°C) and were restarted upon the improvement of symptoms at the same dose if patients remained symptom free (temperature \<38°C) for at least 24 hours. In addition, dabrafenib and trametinib could be interrupted in the presence of pyrexia syndrome (i.e. chills, rigours, night sweats, or influenza-like symptoms) without documented temperature ≥38°C for cases of suspected recurrent pyrexia, at the investigators' discretion. 2. Follow-up Period - patients were followed for disease relapse through 24 months from first dose date. Moreover, patients were followed for overall survival through withdrawal, lost to follow-up, death, or the end of study, whichever occurs first. The follow-up period started once treatment was completed or treatment was prematurely discontinued.

Conditions

• Malignant Melanoma

Interventions

Type	Name	Description
DRUG	Dabrafenib	Supplied as dabrafenib 50 mg and 75 mg capsules for oral administration
DRUG	Trametinib	Supplied as trametinib 0.5mg, and 2.0mg tablets for oral administration

Timeline

• Start date: 2018-08-29
• Primary completion: 2020-10-05
• Completion: 2021-09-16
• First posted: 2018-06-11
• Last updated: 2025-04-29
• Results posted: 2024-03-18

Locations

100 sites across 23 countries: Argentina, Australia, Brazil, Canada, Czechia, Finland, France, Greece, Hungary, Israel, Italy, Japan, Latvia, Lithuania, Norway, Poland, Portugal, Russia, Slovakia, Slovenia, Sweden, Turkey (Türkiye), United Kingdom