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Hydralazine Valproate for Cervical Cancer

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ClinicalTrials.gov 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
Sponsor:
Collaborator:
Psicofarma S.A. de C.V.
Information provided by:
National Institute of Cancerología

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.


Condition or disease Intervention/treatment Phase
Metastatic Cervical Cancer Drug: Hydralazine and magnesium valproate Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 143 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 Recurrent and Metastatic Cervical Cancer.
Study Start Date : July 2007
Estimated Primary Completion Date : September 2010
Estimated Study Completion Date : December 2010


Arm Intervention/treatment
Placebo Comparator: 1 Drug: Placebo
Cisplatin + Topotecan plus placebo
Other Name: TRANSKRIP R/L

Experimental: 2 Drug: Hydralazine and magnesium valproate
Cisplatin + Topotecan plus hydralazine valproate
Other Name: TRANSKRIP R/L




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 2-years ]

Secondary Outcome Measures :
  1. Response rate, safety, overall survival. [ Time Frame: 2-years ]


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

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.

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 ClinicalTrials.gov identifier (NCT number): NCT00532818


Contacts
Contact: Alfonso Dueñas-Gonzalez, MD PhD +5255 56280486 alfonso_duenasg@yahoo.com

Locations
Mexico
Instituto Nacional de Cancerologia Recruiting
Mexico City, Distrito Federal, Mexico, 14080
Principal Investigator: Lucely Cetina, MD         
Sponsors and Collaborators
National Institute of Cancerología
Psicofarma S.A. de C.V.
Investigators
Study Chair: Myrna Candelaria, MD Instituto Nacional de Cancerologia, Columbia

Responsible Party: Lucely Cetina, Instituto Nacional de Cancerologia
ClinicalTrials.gov Identifier: NCT00532818     History of Changes
Other Study ID Numbers: 006/027/ICI
First Posted: September 20, 2007    Key Record Dates
Last Update Posted: March 30, 2009
Last Verified: March 2009

Keywords provided by National Institute of Cancerología:
Epigenetic therapy
Hydralazine
Valproate
Cervical cancer
Randomized
Phase III

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Valproic Acid
Hydralazine
Anticonvulsants
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