Hydralazine Valproate for Ovarian Cancer

NCT00533299 | Unknown Phase 3 DMC

• 1 other identifier: 006/028/DDI
• Study Type: interventional
• Target: 211
• Locations: 1 country
• Sites: 1

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.

Conditions

Ovarian Cancer

Keywords

Epigenetics, hydralazine, valproate, ovarian cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  2-years

Secondary Outcomes (1)

• Safety, response, overall survival.

  2-years

Study Arms (2)

1

EXPERIMENTAL

Topotecan hydralazine valproate

Drug: Hydralazine and magnesium valproate

2

PLACEBO COMPARATOR

Placebo, hydralazine, valproate

Drug: Placebo

Interventions

Hydralazine and magnesium valproate DRUG

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.

1

Placebo DRUG

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.

2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Cancerología: lead

Study Sites (1)

Instituto Nacional de Cancerologia

Mexico City, Tlalpan, 14080, Mexico

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Hydralazine; Valproic Acid

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Dolores Gallardo, MD

  Instituto Nacional de Cancerologia, Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alfonso Dueñas-Gonzalez, MD PhD

CONTACT

+5255 56280486

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: September 19, 2007
• First Posted: September 21, 2007
• Study Start: August 1, 2007
• Study Completion: December 1, 2009
• Last Updated: September 21, 2007

Record last verified: 2007-08

Locations

ME (1)