Hydralazine Valproate for Ovarian Cancer

September 20, 2007 updated by: National Institute of Cancerología

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.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

211

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Alfonso Dueñas-Gonzalez, MD PhD
  • Phone Number: +5255 56280486

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-Free Survival
Time Frame: 2-years
2-years

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety, response, overall survival.
Time Frame: 2-years
2-years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Cancerología

Investigators

  • Principal Investigator: Dolores Gallardo, MD, Instituto Nacional de Cancerologia, Columbia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Study Completion (Anticipated)

December 1, 2009

Study Registration Dates

First Submitted

September 19, 2007

First Submitted That Met QC Criteria

September 20, 2007

First Posted (Estimate)

September 21, 2007

Study Record Updates

Last Update Posted (Estimate)

September 21, 2007

Last Update Submitted That Met QC Criteria

September 20, 2007

Last Verified

August 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 006/028/DDI

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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