Hydralazine Valproate for Ovarian Cancer

Phase 3

• Conditions: Ovarian Cancer
• Interventions: Drug: Hydralazine and magnesium valproate; Drug: Placebo

• Registration Number: NCT00533299
• Lead Sponsor: National Institute of Cancerología

Brief Summary

The current standard for recurrent, persistent or metastatic cisplatin-resistant ovarian cancer is palliative chemotherapy with either topotecan, liposomal doxorubicin or gemcitabine, 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 topotecan over placebo plus topotecan upon progression-free survival.

Hypothesis. Hydralazine and magnesium valproate associated to topotecan will increase progression-free survival from 6 to 9 months as compared with the same regimen of chemotherapy plus placebo.

Detailed Description

Randomized, double-blind phase III trial. A total of 211 patients (alpha 0.5, power 0.8)with cisplatin-resistant recurrent or persistent cancer will be randomized to topotecan + placebo or topotecan + hydralazine + valproate for 6 courses every 4 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 Timeline

• Status Verified: 2007-08
• Study Start: 2007-08
• Study First Submitted: 2007-09-19
• Study First Submitted QC: 2007-09-20
• Last Update Submitted: 2007-09-20
• Study First Posted: 2007-09-21
• Last Update Posted: 2007-09-21
• Study Completion: 2009-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 211

Inclusion Criteria

• Measurable or evaluable disease(evaluable according to CA125 criteria of GCIG) Cisplatin resistant ovarian cancer
• Persistent or progression to first line platinum-based chemotherapy
• Relapse within 6 months after completing first line platinum-based chemotherapy
• Platinum-sensitive disease who are failed to second line therapy based on platinum.
• Adequate organic 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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Hydralazine and magnesium valproate	Topotecan hydralazine valproate
2	Placebo	Placebo, hydralazine, valproate

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	2-years

Secondary Outcome Measures

Name	Time	Method
Safety, response, overall survival.	2-years

Trial Locations

Locations (1)

Instituto Nacional de Cancerologia; 🇲🇽 Mexico City, Tlalpan, Mexico