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Sponsors and Collaborators: |
National Institute of Cancerología CONACYT PSICOFARMA S.A.DE C.V |
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Information provided by: | National Institute of Cancerología |
ClinicalTrials.gov Identifier: | NCT00404326 |
The current standard for locally advanced cervical cancer is concurrent cisplatin-based chemotherapy, however, the treatment 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 radiation and chemotherapy effects.
Objective. To determine response rate, safety and biological effects of hydralazine and magnesium valproate when added to cisplatin chemoradiation.
Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase the clinical complete response rate to 95% as compared to 75% as seen in historical controls treated with cisplatin chemoradiation in FIGO stage IIIB patients.
Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical carcinoma with no previous treatment will be included. Patients will be typed for acetylator status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at 40mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy). Clinical response rate, safety and transcriptome changes will be analyzed.
Condition | Intervention | Phase |
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Cervical Cancer |
Drug: Hydralazine and magnesium valproate Procedure: Punch biopsy of the primary tumor |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Official Title: | A Phase II Study of Transcriptional Therapy With the DNA Demethylating Hydralazine and the HDAC Inhibitor Valproate Associated to Concomitant Cisplatin Chemoradiation in FIGO Stage III Cervical Cancer. |
Estimated Enrollment: | 18 |
Study Start Date: | May 2005 |
Estimated Study Completion Date: | November 2006 |
Eligible patients after signing informed consent will undergo study evaluation and then typed for acetylator phenotype before receive either 182 or 83 mg of hydralazine, and magnesium valproate at 30mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy. External beam radiation will be delivered by megavoltage equipment for a dose of 50gy (2Gy fraction from monday to friday) concurrently with cisplatin at 40mg/m2 for six weeks. Within one to two weeks, intracavitary brachytherapy (low-dose rate, Cesium sources) will be delivered to achieve at least 85Gy to point A. A punch biopsy from the primary tumor will be taken at entering the study and at day 8 of hydralazine and valproate treatment (before the first dose of cisplatin and radiation)to assess global gene expression profiling by microarray analysis. Blood samples will be taken to assess global DNA methylation, histone deacetylase activity and plasma levels of hydralazine and valproic acid.
Clinical response and toxicity will be assessed.
Ages Eligible for Study: | 18 Years to 70 Years |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Mexico, TLALPAN | |
National Institute of Cancerologia | |
MEXICO CITY, TLALPAN, Mexico, 14080 |
Study Director: | Alfonso Duenas-Gonzalez, MD, PhD. | National Institute of Cancerologia, Mexico |
Study ID Numbers: | 005/013/ICI |
Study First Received: | November 25, 2006 |
Last Updated: | November 27, 2006 |
ClinicalTrials.gov Identifier: | NCT00404326 |
Health Authority: | Mexico: Ethics Committee |
Cervical carcinoma Epigenetic therapy Hydralazine Valproate Microarray analysis |
Cisplatin Hydralazine Valproic Acid Carcinoma |
Vasodilator Agents Neurotransmitter Agents Tranquilizing Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Psychotropic Drugs Central Nervous System Depressants Enzyme Inhibitors |
Cardiovascular Agents Antihypertensive Agents Antimanic Agents Pharmacologic Actions Therapeutic Uses GABA Agents Central Nervous System Agents Anticonvulsants |