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.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Global DNA methylation
Claudia Arce, MD
Principal Investigator
Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico
Mexico: Ethics Committee
005/012/ICI
NCT00395655
June 2005
August 2006
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