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Hydralazine Valproate for Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status

Unknown status

Phase

Phase 3

Locations

Mexico

Study Type

Interventional

Intervention

Hydralazine and magnesium valproate

Placebo

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Epigenetics, hydralazine, valproate, ovarian cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Instituto Nacional de CancerologiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Topotecan hydralazine valproate

Placebo, hydralazine, valproate

Outcomes

Primary Outcome Measures

Progression-Free Survival

Secondary Outcome Measures

Safety, response, overall survival.

Full Information

NCT ID

NCT00533299

First Posted

September 19, 2007

Last Updated

September 20, 2007

Sponsor

National Institute of Cancerología

1. Study Identification

Unique Protocol Identification Number

NCT00533299

Brief Title

Hydralazine Valproate for Ovarian Cancer

Official Title

Randomized, Double-Blind, Phase III Trial of Chemotherapy Plus the Transcriptional Therapy Hydralazine and Magnesium Valproate Versus Chemotherapy Plus Placebo in Cisplatin-Resistant Recurrent Ovarian Cancer.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2007

Overall Recruitment Status

Unknown status

Study Start Date

August 2007 (undefined)

Primary Completion Date

undefined (undefined)

Study Completion Date

December 2009 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

National Institute of Cancerología

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ovarian Cancer

Keywords

Epigenetics, hydralazine, valproate, ovarian cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

211 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Topotecan hydralazine valproate

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo, hydralazine, valproate

Intervention Type

Drug

Intervention Name(s)

Hydralazine and magnesium valproate

Intervention Description

Hydralazine and valproate will start from seven days before day 1 of chemotherapy until the end of the sixth course. Hydralazine will be administered at 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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebos will start from seven days before day 1 of chemotherapy until the end of the sixth course. Placebo tablets will be administered in an identical form that experimental drugs.

Primary Outcome Measure Information:

Title

Progression-Free Survival

Time Frame

2-years

Secondary Outcome Measure Information:

Title

Safety, response, overall survival.

Time Frame

2-years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Alfonso Dueñas-Gonzalez, MD PhD

Phone

+5255 56280486

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dolores Gallardo, MD

Organizational Affiliation

Instituto Nacional de Cancerologia, Columbia

Official's Role

Principal Investigator

Facility Information:

Facility Name

Instituto Nacional de Cancerologia

City

Mexico City

State/Province

Tlalpan

ZIP/Postal Code

14080

Country

Mexico

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dolores Gallardo, MD

12. IPD Sharing Statement

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Hydralazine Valproate for Ovarian Cancer

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