Hydralazine Valproate for Ovarian Cancer
Recruitment status was Recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Ovarian Cancer |
Drug: Hydralazine and magnesium valproate Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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. |
- Progression-Free Survival [ Time Frame: 2-years ]
- Safety, response, overall survival. [ Time Frame: 2-years ]
| Estimated Enrollment: | 211 |
| Study Start Date: | August 2007 |
| Estimated Study Completion Date: | December 2009 |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Topotecan hydralazine valproate
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Drug: Hydralazine and magnesium valproate
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.
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Placebo Comparator: 2
Placebo, hydralazine, valproate
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Drug: Placebo
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.
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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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Alfonso Dueñas-Gonzalez, MD PhD | +5255 56280486 |
| Mexico | |
| Instituto Nacional de Cancerologia | Recruiting |
| Mexico City, Tlalpan, Mexico, 14080 | |
| Principal Investigator: Dolores Gallardo, MD | |
| Principal Investigator: | Dolores Gallardo, MD | Instituto Nacional de Cancerologia, Columbia |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00533299 History of Changes |
| Other Study ID Numbers: | 006/028/DDI |
| Study First Received: | September 19, 2007 |
| Last Updated: | September 20, 2007 |
| Health Authority: | Mexico: Ethics Committee |
Keywords provided by National Institute of Cancerología:
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Epigenetics, hydralazine, valproate, ovarian cancer |
Additional relevant MeSH terms:
|
Ovarian Neoplasms Endocrine Gland Neoplasms Neoplasms by Site Neoplasms Ovarian Diseases Adnexal Diseases Genital Diseases, Female Genital Neoplasms, Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Valproic Acid Hydralazine Anticonvulsants Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action GABA Agents Neurotransmitter Agents Physiological Effects of Drugs Antimanic Agents Tranquilizing Agents Central Nervous System Depressants Psychotropic Drugs Antihypertensive Agents Cardiovascular Agents Vasodilator Agents |
ClinicalTrials.gov processed this record on May 23, 2013