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.
18 Years
70 Years
Female
Cervical Cancer
Trial Information
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.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Clinical Response
Principal Investigator
Alfonso Duenas-Gonzalez, MD, PhD.
Investigator Role:
Study Director
Investigator Affiliation:
National Institute of Cancerologia, Mexico
Authority:
Mexico: Ethics Committee
Study ID:
005/013/ICI
NCT ID:
NCT00404326
Start Date:
May 2005
Completion Date:
November 2006
Related Keywords:
- Cervical Cancer
- Cervical carcinoma
- Epigenetic therapy
- Hydralazine
- Valproate
- Microarray analysis
- Uterine Cervical Neoplasms
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