Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer
Information source: National Institute of Cancerología
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cervical Cancer
Intervention: Hydralazine and magnesium valproate (Drug); Punch biopsy of the primary tumor (Procedure)
Phase: Phase 2
Sponsored by: National Institute of Cancerología
Official(s) and/or principal investigator(s):
Alfonso Duenas-Gonzalez, MD, PhD., Study Director, Affiliation: National Institute of Cancerologia, Mexico
The current standard for locally advanced cervical cancer is concurrent cisplatin-based
chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations
play an important role in cancer progression by silencing growth regulatory genes and there
is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the
radiation and chemotherapy effects.
Objective. To determine response rate, safety and biological effects of hydralazine and
magnesium valproate when added to cisplatin chemoradiation.
Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase
the clinical complete response rate to 95% as compared to 75% as seen in historical controls
treated with cisplatin chemoradiation in FIGO stage IIIB patients.
Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical
carcinoma with no previous treatment will be included. Patients will be typed for acetylator
status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at
40mg/Kg from day - 7 to the end of chemoradiation (external and brachytherapy). Clinical
response rate, safety and transcriptome changes will be analyzed.
Official title: 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.
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Gene expression profiling
Global DNA methylation
Plasma levels hydralazine and valproic acid
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.
Minimum age: 18 Years.
Maximum age: 70 Years.
- informed consent, histological diagnosis of cervical carcinoma (epidermoid,
adenoesquamous and adenocarcinoma), clinical stage III B, untreated, aged 18-70
years, performance status 0-2 according to ECOG classification, and adequate liver,
hematological and renal function, as defined by: hemoglobin >10 g/L, leukocytes
>4000/mm3, platelets >100 000mm3; normal creatinine value and creatinine clearance
>60 mL/min; total bilirubin < 1. 5 upper normal limit value; no evidence of systemic
disease or para-aortic lymph node involvement.
- History of allergy to hydralazine or valproate; past or present condition of
rheumatic disease, central nervous system disease, heart failure from aortic stenosis
and postural hypotension as diagnosed by a physician; previous use of the
experimental drugs (hydralazine and magnesium valproate) as well as if patients were
pregnant or breast-feeding. Other exclusion criteria included uncontrolled systemic
disease or infection.
Locations and Contacts
National Institute of Cancerologia, Mexico City, Tlalpan 14080, Mexico
Starting date: May 2005
Last updated: November 27, 2006