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Hydralazine Valproate for Ovarian Cancer

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

Tracking Information
First Submitted Date  ICMJE September 19, 2007
First Posted Date  ICMJE September 21, 2007
Last Update Posted Date September 21, 2007
Study Start Date  ICMJE August 2007
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2007)
Progression-Free Survival [ Time Frame: 2-years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2007)
Safety, response, overall survival. [ Time Frame: 2-years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Hydralazine Valproate for Ovarian Cancer
Official Title  ICMJE 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.
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ovarian Cancer
Intervention  ICMJE
  • 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.
  • 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.
Study Arms  ICMJE
  • Experimental: 1
    Topotecan hydralazine valproate
    Intervention: Drug: Hydralazine and magnesium valproate
  • Placebo Comparator: 2
    Placebo, hydralazine, valproate
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 20, 2007)
211
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2009
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00533299
Other Study ID Numbers  ICMJE 006/028/DDI
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Cancerología
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dolores Gallardo, MD Instituto Nacional de Cancerologia, Columbia
PRS Account National Institute of Cancerología
Verification Date August 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP