Vorinostat in patients with resistant BRAFV600E mutated advanced melanoma: a proof of concept study.
Future Oncol
; 16(11): 619-629, 2020 Apr.
Article
in En
| MEDLINE
| ID: mdl-32125175
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).
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Proto-Oncogene Proteins B-raf
/
Histone Deacetylase Inhibitors
/
Vorinostat
/
Melanoma
Limits:
Humans
Language:
En
Journal:
Future Oncol
Year:
2020
Document type:
Article
Affiliation country:
Netherlands