Hydralazine Valproate for Cervical Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2009 by National Institute of Cancerología.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Psicofarma S.A. de C.V.
Information provided by:
National Institute of Cancerología
ClinicalTrials.gov Identifier:
NCT00532818
First received: September 18, 2007
Last updated: March 27, 2009
Last verified: March 2009
  Purpose

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 Intervention Phase
Metastatic Cervical Cancer
Drug: Hydralazine and magnesium valproate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by National Institute of Cancerología:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate, safety, overall survival. [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 143
Study Start Date: July 2007
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Additional Information:
No publications provided

Responsible Party: Lucely Cetina, Instituto Nacional de Cancerologia
ClinicalTrials.gov Identifier: NCT00532818     History of Changes
Other Study ID Numbers: 006/027/ICI
Study First Received: September 18, 2007
Last Updated: March 27, 2009
Health Authority: Mexico: Ethics Committee

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

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Hydralazine
Valproic Acid
Anticonvulsants
Antihypertensive Agents
Antimanic Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 30, 2014