A Phase II Study of Transcriptional Therapy With the DNA Demethylating Hydralazine and the HDAC Inhibitor Valproate Associated to Concomitant Cisplatin Chemoradiation in FIGO Stage III Cervical Cancer.
Eligible patients after signing informed consent will undergo study evaluation and then
typed for acetylator phenotype before receive either 182 or 83 mg of hydralazine, and
magnesium valproate at 30mg/Kg from day -7 to the end of chemoradiation (external and
brachytherapy. External beam radiation will be delivered by megavoltage equipment for a dose
of 50gy (2Gy fraction from monday to friday) concurrently with cisplatin at 40mg/m2 for six
weeks. Within one to two weeks, intracavitary brachytherapy (low-dose rate, Cesium sources)
will be delivered to achieve at least 85Gy to point A. A punch biopsy from the primary tumor
will be taken at entering the study and at day 8 of hydralazine and valproate treatment
(before the first dose of cisplatin and radiation)to assess global gene expression profiling
by microarray analysis. Blood samples will be taken to assess global DNA methylation,
histone deacetylase activity and plasma levels of hydralazine and valproic acid.
Clinical response and toxicity will be assessed.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Alfonso Duenas-Gonzalez, MD, PhD.
National Institute of Cancerologia, Mexico
Mexico: Ethics Committee