Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 and over	Other	006/027/ICI NCT00532818

Trial Description

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.

Further Study Information

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 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.

Trial Contact Information

Trial Lead Organizations/Sponsors

Instituto Nacional de Cancerologia

Myrna Candelaria, MD

Study Chair

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

Mexico
	MEXICO CITY
	Instituto Nacional de Cancerologia
		Lucely Cetina, MD	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00532818
Information obtained from ClinicalTrials.gov on March 29, 2009