Patients with BRAF V600 mutant advanced melanoma benefit from treatment with a BRAF-inhibitor (e.g. dabrafenib, vemurafenib) and from combination of a BRAF- and MEK-inhibitor (e.g. dabrafenib and trametinib). Following initial tumor regression, progression is diagnosed in a majority of patients treated with BRAF-inhibitor mono-therapy within the first 12-months of therapy. Various molecular mechanisms that underlie the development of resistance to treatment with a BRAF-inhibitor have been reported. These mechanisms do not include secondary mutations in the BRAF-gene and therefore resistance to BRAF-inhibition could potentially be reversible when selective pressure by BRAF-inhibition is withheld for a sufficient period of time of melanoma progression. This clinical trial protocol addresses the potential renewed anti-tumor activity of combined BRAF- and MEK inhibition with the combination of dabrafenib and trametinib in patients with unresectable AJCC stage III or - IV BRAF V600 mutant melanoma who are documented with progression of disease at least 12 weeks following the last day of dosing of a BRAFinhibitor containing treatment regimen.
Name: Dabrafenib + TrametinibType: Drug
Dabrafenib + trametinib
Description: Detect adverse eventsMeasure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability Time: Participants will be monitored until progression, with an expected average of 6 months
Description: To explore if tumor specific cfDNA levels can be used as a monitoring tool to detect early progression of diseaseMeasure: Tumour-specific cfDNA levels Time: Participants will be monitored until progression, with an expected average of 6 months
Single Group Assignment
There is one SNP
2. Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive. --- V600E ---