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Hydralazine and Valproate Added to Chemotherapy for Breast Cancer

This study has been terminated.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00395655
First Posted: November 3, 2006
Last Update Posted: November 3, 2006
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Council of Science and Technology, Mexico
Psicofarma S.A. de C.V.
Information provided by:
National Institute of Cancerología
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institute of Cancerología:

Primary Outcome Measures:
  • Global DNA methylation
  • Histone Deacetylase Activity
  • Global gene expression

Secondary Outcome Measures:
  • Pathological response
  • Hydralazine plasma levels
  • Valproic acid plasma levels

Estimated Enrollment: 43
Study Start Date: June 2005
Estimated Study Completion Date: August 2006
Detailed Description:
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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00395655


Locations
Mexico
Instituto Nacional de Cancerologia
Mexico City, Tlalpan, Mexico, 14080
Sponsors and Collaborators
National Institute of Cancerología
National Council of Science and Technology, Mexico
Psicofarma S.A. de C.V.
Investigators
Principal Investigator: Claudia Arce, MD Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00395655     History of Changes
Other Study ID Numbers: 005/012/ICI
First Submitted: November 1, 2006
First Posted: November 3, 2006
Last Update Posted: November 3, 2006
Last Verified: November 2006

Keywords provided by National Institute of Cancerología:
locally advanced breast cancer
hydralazine
magnesium valproate
epigenetic therapy
gene expression

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Valproic Acid
Hydralazine
Anticonvulsants
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
Vasodilator Agents