NCT00395655

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (planned)
• Sponsor: National Institute of Cancerología · Other Government
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Locally Advanced Breast Cancer

Interventions

Type	Name	Description
DRUG	Hydralazine and magnesium valproate administration
PROCEDURE	Core-needle biopsy of the breast

Timeline

• Start date: 2005-06-01
• Completion: 2006-08-01
• First posted: 2006-11-03
• Last updated: 2006-11-03

Locations

1 site across 1 country: Mexico