FUTURE ONCOLOGYAHEAD OF PRINTCLINICAL TRIAL PROTOCOL
Vorinostat in patients with resistant BRAFV600E mutated advanced melanoma: a proof of concept study
Sanne Huijberts, Liqin Wang, Rodrigo Leite de Oliveira, Hilde Rosing, Bastiaan Nuijen, Jos Beijnen, Rene Bernards, Jan Schellens & Sofie Wilgenhof
Published Online:3 Mar 2020https://doi.org/10.2217/fon-2020-0023
View Article
Tools
Share
Abstract
The clinical benefit of treatment with BRAF- and MEK-inhibitors in melanoma is limited due to resistance associated with emerging secondary mutations. Preclinical and clinical studies have shown that short-term treatment with the HDAC inhibitor vorinostat can eliminate cells harboring these secondary mutations causing resistance. This proof of concept study is to determine the efficacy of sequential treatment with vorinostat and BRAFi/MEKi in resistant BRAFV600E mutant melanoma. The primary aim is demonstrating anti-tumor response of progressive lesions according to RECIST 1.1. Secondary end points are to determine that emerging resistant clones with a secondary mutation in the MAPK pathway can be detected in circulating tumor DNA and purged by short-term vorinostat treatment. Exploratory end points include pharmacokinetic, pharmacodynamic and pharmacogenetic analyses (NCT02836548).
Keywords:
BRAF inhibitorBRAFV600E mutationhistone deacetylase inhibitorMEK inhibitormelanomametastaticresistance
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
Ετικέτες
Τρίτη 3 Μαρτίου 2020
Vorinostat in patients with resistant BRAFV600E mutated advanced melanoma: a proof of concept study
Αναρτήθηκε από
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
στις
10:28 μ.μ.
Ετικέτες
00302841026182,
00306932607174,
alsfakia@gmail.com,
Anapafseos 5 Agios Nikolaos 72100 Crete Greece,
Medicine by Alexandros G. Sfakianakis,
Telephone consultation 11855 int 1193
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου