Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer - Full Text View

Sponsors and Collaborators:	National Institute of Cancerología CONACYT PSICOFARMA S.A.DE C.V
Information provided by:	National Institute of Cancerología
ClinicalTrials.gov Identifier:	NCT00404326

Purpose

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.

Condition	Intervention	Phase
Cervical Cancer	Drug: Hydralazine and magnesium valproate Procedure: Punch biopsy of the primary tumor	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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.

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Divalproex sodium Hydralazine Valproic acid Hydralazine hydrochloride Valproate Sodium Magnesium

U.S. FDA Resources

Further study details as provided by National Institute of Cancerología:

Primary Outcome Measures:

Clinical Response
Safety

Secondary Outcome Measures:

Gene expression profiling
Global DNA methylation
HDAC activity
Plasma levels hydralazine and valproic acid

Estimated Enrollment:	18
Study Start Date:	May 2005
Estimated Study Completion Date:	November 2006

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00404326

Locations

Mexico, TLALPAN
National Institute of Cancerologia
MEXICO CITY, TLALPAN, Mexico, 14080

Sponsors and Collaborators

National Institute of Cancerología

CONACYT

PSICOFARMA S.A.DE C.V

Investigators

Study Director:

Alfonso Duenas-Gonzalez, MD, PhD.

National Institute of Cancerologia, Mexico

More Information

No publications provided

Study ID Numbers:	005/013/ICI
Study First Received:	November 25, 2006
Last Updated:	November 27, 2006
ClinicalTrials.gov Identifier:	NCT00404326 History of Changes
Health Authority:	Mexico: Ethics Committee

Keywords provided by National Institute of Cancerología:

Cervical carcinoma
Epigenetic therapy
Hydralazine
Valproate
Microarray analysis

Study placed in the following topic categories:

Neurotransmitter Agents
Vasodilator Agents
Tranquilizing Agents
Hydralazine
Psychotropic Drugs
Central Nervous System Depressants
Cardiovascular Agents

Antimanic Agents
Antihypertensive Agents
Valproic Acid
Carcinoma
Cisplatin
Anticonvulsants

Additional relevant MeSH terms:

Vasodilator Agents
Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Hydralazine
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors

Cardiovascular Agents
Antihypertensive Agents
Antimanic Agents
Valproic Acid
Pharmacologic Actions
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on September 03, 2009