Hydralazine Valproate for Cervical Cancer
Recruitment status was Recruiting
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Cervical 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 Recurrent and Metastatic Cervical Cancer. |
- Progression-free survival [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]
- Response rate, safety, overall survival. [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 143 |
| Study Start Date: | July 2007 |
| Estimated Study Completion Date: | December 2010 |
| Estimated Primary Completion Date: | September 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Placebo Comparator: 1 |
Drug: Placebo
Cisplatin + Topotecan plus placebo
Other Name: TRANSKRIP R/L
|
| Experimental: 2 |
Drug: Hydralazine and magnesium valproate
Cisplatin + Topotecan plus hydralazine valproate
Other Name: TRANSKRIP R/L
|
Detailed Description:
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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| Contact: Alfonso Dueñas-Gonzalez, MD PhD | +5255 56280486 | alfonso_duenasg@yahoo.com |
| Mexico | |
| Instituto Nacional de Cancerologia | Recruiting |
| Mexico City, Distrito Federal, Mexico, 14080 | |
| Principal Investigator: Lucely Cetina, MD | |
| Study Chair: | Myrna Candelaria, MD | Instituto Nacional de Cancerologia, Columbia |
More Information
Additional Information:
No publications provided
| Responsible Party: | Lucely Cetina, Instituto Nacional de Cancerologia |
| ClinicalTrials.gov Identifier: | NCT00532818 History of Changes |
| Other Study ID Numbers: | 006/027/ICI |
| Study First Received: | September 18, 2007 |
| Last Updated: | March 27, 2009 |
| Health Authority: | Mexico: Ethics Committee |
Keywords provided by National Institute of Cancerología:
|
Epigenetic therapy Hydralazine Valproate |
Cervical cancer Randomized Phase III |
Additional relevant MeSH terms:
|
Uterine Cervical Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Cervical Diseases Uterine Diseases Genital Diseases, Female 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