NCT04059224

TraMel-WT: A Trial of Trametinib in Patients With Advanced Pretreated BRAFV600 Wild-type Melanoma

TraMel-WT: A Stratified Dual-stratum Open-label Two-stage Phase 2 Trial of Trametinib in Patients With Advanced Pretreated BRAFV600 Wild-type Melanoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Universitair Ziekenhuis Brussel · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase 2 trial will investigate the efficacy and safety of trametinib and dabrafenib in patients with advanced BRAF V600 (v-Raf murine sarcoma viral oncogene homolog B) wild-type melanoma (stratified according to BRAF V600 wild-type/NRAS (neuroblastoma Ras viral oncogene homolog) mutant and BRAF V600 wild-type/NRAS wild-type melanoma patients) that have been pretreated and progressed following treatment with PD-1- (programmed cell death-1) and CTLA-4-blocking (cytotoxic T-lymphocyte-associated antigen 4) immune checkpoint inhibitors. The investigators hypothesize that treatment with trametinib will result in objective antitumor activity. In order to improve the tolerability and optimize the dose intensity of trametinib, a minimal dose of dabrafenib will be added to prevent and manage trametinib-related skin toxicity.

Detailed description

This will be a non-randomized stratified dual-arm open-label two-stage single-centre phase 2 trial. Patients are eligible if they are diagnosed with BRAF V600 (v-Raf murine sarcoma viral oncogene homolog B) wild-type unresectable AJCC (American Joint Committee on Cancer) stage III or IV melanoma and are documented with progression of disease following treatment with a PD-1- (programmed cell death-1) and CTLA-4-blocking (cytotoxic T-lymphocyte-associated antigen 4) immune checkpoint inhibitor or who have a contraindication for treatment with immune checkpoint inhibitors. Patients will be considered for study participation not earlier than 4 weeks after the last dosing of the prior therapy. Patients will be stratified according to their NRAS (neuroblastoma RAS viral oncogene homolog) mutation status: arm A involves patients with advanced pretreated BRAF V600 wild-type/NRAS mutant melanoma; arm B involves patients with advanced pretreated BRAF V600 wild-type/NRAS wild-type melanoma. All patients will be treated with trametinib 2 mg once a day and dabrafenib 50 mg twice a day. Throughout their study participation, patients will be continuously monitored for safety and evaluated for tumor response every 8 weeks or sooner if there is clinical suspicion of progressive disease. Patients will be treated until progression of disease, unacceptable toxicity or withdrawal of consent. The primary endpoint of the study is the objective response rate. Secondary endpoints are progression-free survival, overall survival and safety.

Conditions

• Stage IV Melanoma
• Stage III Melanoma

Interventions

Type	Name	Description
DRUG	Trametinib	Trametinib 2 mg once a day by mouth.
DRUG	Dabrafenib	Dabrafenib 50 mg twice a day by mouth. Dabrafenib can be uptitrated to 150 mg twice a day in case of dose-limiting trametinib-associated skin toxicity.

Timeline

• Start date: 2019-01-28
• Primary completion: 2023-06-30
• Completion: 2023-06-30
• First posted: 2019-08-16
• Last updated: 2023-09-26

Locations

1 site across 1 country: Belgium