Hydralazine Valproate for Cervical Cancer
Information source: National Institute of Cancerología
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Cervical Cancer
Intervention: Hydralazine and magnesium valproate (Drug); Placebo (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: National Institute of Cancerología Official(s) and/or principal investigator(s):
Myrna Candelaria, MD, Study Chair, Affiliation: Instituto Nacional de Cancerologia
Overall contact:
Alfonso Dueñas-Gonzalez, MD PhD, Phone: +5255 56280486, Email: alfonso_duenasg@yahoo.com
Summary
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.
Clinical Details
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.
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: Progression-free survival
Secondary outcome: Response rate, safety, overall survival.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
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.
Locations and Contacts
Alfonso Dueñas-Gonzalez, MD PhD, Phone: +5255 56280486, Email: alfonso_duenasg@yahoo.com
Instituto Nacional De Cancerologia, MEXICO CITY, Distrito Federal 14080, Mexico; Recruiting
Lucely Cetina, MD, Principal Investigator
Additional Information
Starting date: July 2007
Ending date: December 2009
Last updated: September 21, 2007
|
