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Hydralazine Valproate for Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00533299
Recruitment Status : Unknown
Verified August 2007 by National Institute of Cancerología.
Recruitment status was:  Recruiting
First Posted : September 21, 2007
Last Update Posted : September 21, 2007
Information provided by:
National Institute of Cancerología

Brief Summary:

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 or disease Intervention/treatment Phase
Ovarian Cancer Drug: Hydralazine and magnesium valproate Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 211 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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.
Study Start Date : August 2007
Estimated Study Completion Date : December 2009

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. Progression-Free Survival [ Time Frame: 2-years ]

Secondary Outcome Measures :
  1. Safety, response, overall survival. [ Time Frame: 2-years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00533299

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Contact: Alfonso Dueñas-Gonzalez, MD PhD +5255 56280486

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Instituto Nacional de Cancerologia Recruiting
Mexico City, Tlalpan, Mexico, 14080
Principal Investigator: Dolores Gallardo, MD         
Sponsors and Collaborators
National Institute of Cancerología
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Principal Investigator: Dolores Gallardo, MD Instituto Nacional de Cancerologia, Columbia
Layout table for additonal information Identifier: NCT00533299    
Other Study ID Numbers: 006/028/DDI
First Posted: September 21, 2007    Key Record Dates
Last Update Posted: September 21, 2007
Last Verified: August 2007
Keywords provided by National Institute of Cancerología:
Epigenetics, hydralazine, valproate, ovarian cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Valproic Acid
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
Vasodilator Agents