Dabrafenib and Trametinib for BRAF-inhibitor Pretreated Patients
Status:
Completed
Trial end date:
2017-12-01
Target enrollment:
Participant gender:
Summary
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.