|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||||||||||||||||||||||||||
| Sponsors and Collaborators: |
National Institute of Cancerología CONACYT PSICOFARMA S.A.DE C.V |
|---|---|
| Information provided by: | National Institute of Cancerología |
| ClinicalTrials.gov Identifier: | NCT00395655 |
Purpose
Aberrant DNA methylation and histone deacetylation participate in cancer development and progression, as epigenetic alterations are common to breast cancer, in this phase II study, the demethylating hydralazine plus the HDAC inhibitor magnesium valproate will be added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy.
| Condition | Intervention | Phase |
|---|---|---|
|
Locally Advanced Breast Cancer |
Drug: Hydralazine and magnesium valproate administration Procedure: Core-needle biopsy of the breast |
Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacodynamics Study |
| Official Title: | A Phase II Clinical Study of Hydralazine and Valproic Acid in Combination With Neoadjuvant Cytotoxic Chemotherapy in Stage IIB and IIIA Breast Carcinoma |
| Estimated Enrollment: | 43 |
| Study Start Date: | June 2005 |
| Estimated Study Completion Date: | August 2006 |
Eligible patients after signing the informed consent and will undergo study evaluation and then typed for acetylator phenotype before being treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ends.
Chemotherapy will consists in a regimen of four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days, followed by surgery to assess the pathological response. Adjuvant radiation and additional treatment will be done in off-protocol basis according to standard institutional policies. Blood samples and core-needle biopsies will be taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. Global cytosine content (global DNA methylation) and histone deacetylase activity will be assessed in peripheral blood DNA. The transcriptional profile in the primary breast tumor before and after treatment will also be analyzed as well as the plasma levels of hydralazine and valproic acid.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Aged 18 and older; histologically proven invasive T2-3, N0-2, and M0 (stages IIB–IIIA) breast carcinoma; Eastern Cooperative Oncology Group performance status ≤2. Hematological function: Absolute leukocyte count ≥4,000/mm3, platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL. Hepatic function: total bilirubin, aspartate amino transferase and alanine amino transferase <1.5 the upper normal limit. Renal function: creatinine ≤1.2 mg/dL or a calculated creatinine clearance of ≥60 mL/min. Written informed consent.
Exclusion Criteria:
A history of allergy to sulphas, hydralazine, or magnesium 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. Previous use of the experimental drugs. Pregnancy and breast-feeding. Uncontrolled systemic disease or infection.
Contacts and Locations| Mexico, TLALPAN | |
| Instituto Nacional De Cancerologia | |
| MEXICO CITY, TLALPAN, Mexico, 14080 | |
| Principal Investigator: | Claudia Arce, MD | Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico |
More Information
| Study ID Numbers: | 005/012/ICI |
| Study First Received: | November 1, 2006 |
| Last Updated: | November 1, 2006 |
| ClinicalTrials.gov Identifier: | NCT00395655 History of Changes |
| Health Authority: | Mexico: Ethics Committee |
|
locally advanced breast cancer hydralazine magnesium valproate epigenetic therapy gene expression |
|
Vasodilator Agents Neurotransmitter Agents Tranquilizing Agents Skin Diseases Hydralazine Psychotropic Drugs Breast Neoplasms Central Nervous System Depressants |
Cardiovascular Agents Antimanic Agents Antihypertensive Agents Valproic Acid Carcinoma Breast Diseases Anticonvulsants |
|
Vasodilator Agents Neurotransmitter Agents Tranquilizing Agents Molecular Mechanisms of Pharmacological Action Skin Diseases Hydralazine Physiological Effects of Drugs Psychotropic Drugs Breast Neoplasms Central Nervous System Depressants Enzyme Inhibitors Cardiovascular Agents |
Antihypertensive Agents Antimanic Agents Valproic Acid Pharmacologic Actions Neoplasms Neoplasms by Site Therapeutic Uses GABA Agents Central Nervous System Agents Anticonvulsants Breast Diseases |
