Hydralazine Valproate for Cervical Cancer

Metastatic Cervical Cancer Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00532818
• Other study ID #: 006/027/ICI
• Status: Recruiting
• Phase: Phase 3
• First received: September 18, 2007
• Last updated: March 27, 2009
• Start date: July 2007
• Est. completion date: December 2010

Study information

• Verified date: March 2009
• Source: National Institute of Cancerología
• Contact: Alfonso Dueñas-Gonzalez, MD PhD
• Phone: +5255 56280486
• Email: alfonso_duenasg[@]yahoo.com
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 143
• Est. completion date: December 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• Hydralazine and magnesium valproate
Cisplatin + Topotecan plus hydralazine valproate
• Placebo
Cisplatin + Topotecan plus placebo

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerologia	Mexico City	Distrito Federal

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Cancerología	Psicofarma S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		2-years	Yes
Secondary	Response rate, safety, overall survival.		2-years	Yes

External Links

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