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A Phase II Clinical Study of Hydralazine and Valproic Acid in Combination With Neoadjuvant Cytotoxic Chemotherapy in Stage IIB and IIIA Breast Carcinoma

Phase 2
18 Years
Not Enrolling
Locally Advanced Breast Cancer

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Trial Information

A Phase II Clinical Study of Hydralazine and Valproic Acid in Combination With Neoadjuvant Cytotoxic Chemotherapy in Stage IIB and IIIA Breast Carcinoma

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.

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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Global DNA methylation

Principal Investigator

Claudia Arce, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico


Mexico: Ethics Committee

Study ID:




Start Date:

June 2005

Completion Date:

August 2006

Related Keywords:

  • Locally Advanced Breast Cancer
  • locally advanced breast cancer
  • hydralazine
  • magnesium valproate
  • epigenetic therapy
  • gene expression
  • Breast Neoplasms