Hydralazine Valproate for Cervical Cancer - Full Text View

Sponsor:	National Institute of Cancerología
Collaborator:	Psicofarma S.A. de C.V.
Information provided by:	National Institute of Cancerología
ClinicalTrials.gov Identifier:	NCT00532818

Purpose

The current standard for recurrent, persistent or metastatic cervical cancer is palliative chemotherapy with cisplatin topotecan, however, the 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 cytotoxicity of chemotherapy.

Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate plus standard cisplatin topotecan against placebo plus cisplatin topotecan upon progression-free survival.

Hypothesis. Hydralazine and magnesium valproate associated to cisplatin topotecan will increase progression-free survival from 4.6 to 7.6 months as compared with the same regimen of chemotherapy plus placebo.

Condition	Intervention	Phase
Metastatic Cervical Cancer	Drug: Hydralazine and magnesium valproate Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Randomized, Double-Blind, Phase III Trial of Chemotherapy Plus the Transcriptional Therapy Hydralazine and Magnesium Valproate Versus Chemotherapy Plus Placebo in Recurrent and Metastatic Cervical Cancer.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer

Drug Information available for: 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:

Progression-free survival [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate, safety, overall survival. [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	143
Study Start Date:	July 2007
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 1	Drug: Placebo Cisplatin + Topotecan plus placebo Other Name: TRANSKRIP R/L
Experimental: 2	Drug: Hydralazine and magnesium valproate Cisplatin + Topotecan plus hydralazine valproate Other Name: TRANSKRIP R/L

Detailed Description:

Randomized, double-blind phase III trial. A total of 143 patients (alpha 0.5, power 0.8)with metastatic, persistent or recurrent cervical cancer without previous systemic treatment will be randomized to cisplatin topotecan + placebo or cisplatin topotecan hydralazine valproate for 6 courses every 3 weeks. Patients will receive an oral dose of hydralazine of 182mg (rapid) or 83mg (slow) according to the acetylator phenotype in a single daily dose and magnesium valproate at an oral dose of 40mg/Kg t.i.d. Both drugs in a slow-release formulation. Experimental drugs or placebo will start from seven days before day 1 of chemotherapy until the end of the sixth course.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

informed consent, histological diagnosis of persistent, recurrent or metastatic cervical carcinoma; measurable disease by physical examination, CT Scan, MRI or PET-CT. Biopsy is required for confirmation only if the lesion is unique, has less than 2cm in the longest diameter or has no clearly defined borders.
Patients should have no previous systemic treatment (could have received chemotherapy as radiosensitization to the pelvis and or para-aortic field.
Aged >18 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.

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; newly diagnosed hypertension patients with or without pharmacological treatment are allowed as long as their treatment do not include hydralazine.
Previous use of the experimental drugs (hydralazine and magnesium valproate) as well as if patients were pregnant or breast-feeding. Other exclusion criteria are uncontrolled systemic disease or infection.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532818

Contacts

Contact: Alfonso Dueñas-Gonzalez, MD PhD

+5255 56280486

alfonso_duenasg@yahoo.com

Locations

Mexico
Instituto Nacional de Cancerologia	Recruiting
Mexico City, Distrito Federal, Mexico, 14080
Principal Investigator: Lucely Cetina, MD

Sponsors and Collaborators

National Institute of Cancerología

Psicofarma S.A. de C.V.

Investigators

Study Chair:

Myrna Candelaria, MD

Instituto Nacional de Cancerologia, Columbia

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Lucely Cetina, Instituto Nacional de Cancerologia
ClinicalTrials.gov Identifier:	NCT00532818 History of Changes
Other Study ID Numbers:	006/027/ICI
Study First Received:	September 18, 2007
Last Updated:	March 27, 2009
Health Authority:	Mexico: Ethics Committee

Keywords provided by National Institute of Cancerología:

Epigenetic therapy
Hydralazine
Valproate

Cervical cancer
Randomized
Phase III

Additional relevant MeSH terms:

Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Valproic Acid
Hydralazine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses

Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Antihypertensive Agents
Cardiovascular Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on February 12, 2012