Hydralazine and Valproate Added to Chemotherapy for Breast Cancer

This study has been terminated.
Sponsor:
Collaborators:
National Council of Science and Technology, Mexico
Psicofarma S.A. de C.V.
Information provided by:
National Institute of Cancerología
ClinicalTrials.gov Identifier:
NCT00395655
First received: November 1, 2006
Last updated: NA
Last verified: November 2006
History: No changes posted

November 1, 2006
November 1, 2006
June 2005
Not Provided
  • Global DNA methylation
  • Histone Deacetylase Activity
  • Global gene expression
Same as current
No Changes Posted
  • Pathological response
  • Hydralazine plasma levels
  • Valproic acid plasma levels
Same as current
Not Provided
Not Provided
 
Hydralazine and Valproate Added to Chemotherapy for Breast Cancer
A Phase II Clinical Study of Hydralazine and Valproic Acid in Combination With Neoadjuvant Cytotoxic Chemotherapy in Stage IIB and IIIA Breast Carcinoma

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Locally Advanced Breast Cancer
  • Drug: Hydralazine and magnesium valproate administration
  • Procedure: Core-needle biopsy of the breast
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
43
August 2006
Not Provided

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.

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Mexico
 
NCT00395655
005/012/ICI
Not Provided
Not Provided
National Institute of Cancerología
  • National Council of Science and Technology, Mexico
  • Psicofarma S.A. de C.V.
Principal Investigator: Claudia Arce, MD Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico
National Institute of Cancerología
November 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP