Hydralazine Valproate for Ovarian Cancer - Full Text View

Sponsor:	National Institute of Cancerología
Information provided by:	National Institute of Cancerología
ClinicalTrials.gov Identifier:	NCT00533299

Purpose

The current standard for recurrent, persistent or metastatic cisplatin-resistant ovarian cancer is palliative chemotherapy with either topotecan, liposomal doxorubicin or gemcitabine, 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 topotecan over placebo plus topotecan upon progression-free survival.

Hypothesis. Hydralazine and magnesium valproate associated to topotecan will increase progression-free survival from 6 to 9 months as compared with the same regimen of chemotherapy plus placebo.

Condition	Intervention	Phase
Ovarian 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 Cisplatin-Resistant Recurrent Ovarian Cancer.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian 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 ]

Secondary Outcome Measures:

Safety, response, overall survival. [ Time Frame: 2-years ]

Estimated Enrollment:	211
Study Start Date:	August 2007
Estimated Study Completion Date:	December 2009

Arms	Assigned Interventions
Experimental: 1 Topotecan hydralazine valproate	Drug: Hydralazine and magnesium valproate Hydralazine and valproate will start from seven days before day 1 of chemotherapy until the end of the sixth course. Hydralazine will be administered at 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.
Placebo Comparator: 2 Placebo, hydralazine, valproate	Drug: Placebo Placebos will start from seven days before day 1 of chemotherapy until the end of the sixth course. Placebo tablets will be administered in an identical form that experimental drugs.

Detailed Description:

Randomized, double-blind phase III trial. A total of 211 patients (alpha 0.5, power 0.8)with cisplatin-resistant recurrent or persistent cancer will be randomized to topotecan + placebo or topotecan + hydralazine + valproate for 6 courses every 4 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:

Measurable or evaluable disease(evaluable according to CA125 criteria of GCIG) Cisplatin resistant ovarian cancer
Persistent or progression to first line platinum-based chemotherapy
Relapse within 6 months after completing first line platinum-based chemotherapy
Platinum-sensitive disease who are failed to second line therapy based on platinum.
Adequate organic 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: NCT00533299

Contacts

Contact: Alfonso Dueñas-Gonzalez, MD PhD

+5255 56280486

Locations

Mexico
Instituto Nacional de Cancerologia	Recruiting
Mexico City, Tlalpan, Mexico, 14080
Principal Investigator: Dolores Gallardo, MD

Sponsors and Collaborators

National Institute of Cancerología

Investigators

Principal Investigator:

Dolores Gallardo, MD

Instituto Nacional de Cancerologia, Columbia

More Information

No publications provided

ClinicalTrials.gov Identifier:	NCT00533299 History of Changes
Other Study ID Numbers:	006/028/DDI
Study First Received:	September 19, 2007
Last Updated:	September 20, 2007
Health Authority:	Mexico: Ethics Committee

Keywords provided by National Institute of Cancerología:

Epigenetics, hydralazine, valproate, ovarian cancer

Additional relevant MeSH terms:

Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
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