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Hydralazine Valproate for Cervical 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: NCT00532818
Recruitment Status : Unknown
Verified March 2009 by National Institute of Cancerología.
Recruitment status was:  Recruiting
First Posted : September 20, 2007
Last Update Posted : March 30, 2009
Psicofarma S.A. de C.V.
Information provided by:
National Institute of Cancerología

Tracking Information
First Submitted Date  ICMJE September 18, 2007
First Posted Date  ICMJE September 20, 2007
Last Update Posted Date March 30, 2009
Study Start Date  ICMJE July 2007
Estimated Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2007)
Progression-free survival [ Time Frame: 2-years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00532818 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2007)
Response rate, safety, 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 Cervical 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 Recurrent and Metastatic Cervical Cancer.
Brief Summary

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.

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.
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 Metastatic Cervical Cancer
Intervention  ICMJE
  • Drug: Hydralazine and magnesium valproate
    Cisplatin + Topotecan plus hydralazine valproate
    Other Name: TRANSKRIP R/L
  • Drug: Placebo
    Cisplatin + Topotecan plus placebo
    Other Name: TRANSKRIP R/L
Study Arms  ICMJE
  • Placebo Comparator: 1
    Intervention: Drug: Placebo
  • Experimental: 2
    Intervention: Drug: Hydralazine and magnesium valproate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 18, 2007)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2010
Estimated Primary Completion Date September 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 NCT00532818
Other Study ID Numbers  ICMJE 006/027/ICI
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lucely Cetina, Instituto Nacional de Cancerologia
Study Sponsor  ICMJE National Institute of Cancerología
Collaborators  ICMJE Psicofarma S.A. de C.V.
Investigators  ICMJE
Study Chair: Myrna Candelaria, MD Instituto Nacional de Cancerologia, Columbia
PRS Account National Institute of Cancerología
Verification Date March 2009

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