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

• Status: Completed
• Trial end date: 2021-09-16
• Target enrollment: 0
• Participant gender: All

Summary

This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes.

Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm.

This study consists of two Periods for Enrolled subjects:

• Treatment Period - subjects will receive up to 12 months of treatment.

• Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Dabrafenib; Trametinib

Criteria

Inclusion Criteria:

• Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)]

• V600E/K mutation positive using a validated local test

• Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.

• Subjects who have previously had Stage III melanoma at any time are not eligible.

• Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

Exclusion Criteria:

• Uveal or mucosal melanoma

• Evidence of metastatic disease including unresectable in-transit metastasis

• Received any prior adjuvant or neoadjuvant treatment, including but not limited to chemotherapy, checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], biologic therapy, vaccine therapy, investigational treatment, or radiotherapy for melanoma

• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ

• History or current evidence of cardiovascular risk

• A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy