Hydralazine and Valproate Added to Chemotherapy for Breast Cancer

Locally Advanced Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00395655
• Other study ID #: 005/012/ICI
• Status: Terminated
• Phase: Phase 2
• First received: November 1, 2006
• Last updated: November 1, 2006
• Start date: June 2005
• Est. completion date: August 2006

Study information

• Verified date: November 2006
• Source: National Institute of Cancerología
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 43
• Est. completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Locally Advanced Breast Cancer

Intervention

Drug:
• Hydralazine and magnesium valproate administration

Procedure:
• Core-needle biopsy of the breast

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerologia	Mexico City	Tlalpan

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Cancerología	National Council of Science and Technology, Mexico, Psicofarma S.A. de C.V.

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global DNA methylation
Primary	Histone Deacetylase Activity
Primary	Global gene expression
Secondary	Pathological response
Secondary	Hydralazine plasma levels
Secondary	Valproic acid plasma levels