Back to resultsHydralazine and Valproate Added to Chemotherapy for Breast Cancer
Primary Purpose
Locally Advanced Breast Cancer
Status
Terminated
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Hydralazine and magnesium valproate administration
Core-needle biopsy of the breast
Sponsored by
About this trial
This is an interventional treatment trial for Locally Advanced Breast Cancer focused on measuring locally advanced breast cancer, hydralazine, magnesium valproate, epigenetic therapy, gene expression
Eligibility Criteria
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.
Sites / Locations
- Instituto Nacional de Cancerologia
Outcomes
Primary Outcome Measures
Global DNA methylation
Histone Deacetylase Activity
Global gene expression
Secondary Outcome Measures
Pathological response
Hydralazine plasma levels
Valproic acid plasma levels
Full Information
NCT ID
NCT00395655
First Posted
November 1, 2006
Last Updated
November 1, 2006
Sponsor
National Institute of Cancerología
Collaborators
National Council of Science and Technology, Mexico, Psicofarma S.A. de C.V.
1. Study Identification
Unique Protocol Identification Number
NCT00395655
Brief Title
Hydralazine and Valproate Added to Chemotherapy for Breast Cancer
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2006
Overall Recruitment Status
Terminated
Study Start Date
June 2005 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2006 (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
National Institute of Cancerología
Collaborators
National Council of Science and Technology, Mexico, Psicofarma S.A. de C.V.
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Locally Advanced Breast Cancer
Keywords
locally advanced breast cancer, hydralazine, magnesium valproate, epigenetic therapy, gene expression
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Hydralazine and magnesium valproate administration
Intervention Type
Procedure
Intervention Name(s)
Core-needle biopsy of the breast
Primary Outcome Measure Information:
Title
Global DNA methylation
Title
Histone Deacetylase Activity
Title
Global gene expression
Secondary Outcome Measure Information:
Title
Pathological response
Title
Hydralazine plasma levels
Title
Valproic acid plasma levels
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Arce, MD
Organizational Affiliation
Division of Clinical Research, IInstituto Nacional de Cancerologia, Mexico
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Cancerologia
City
Mexico City
State/Province
Tlalpan
ZIP/Postal Code
14080
Country
Mexico
12. IPD Sharing Statement
Citations:
PubMed Identifier
17183730
Citation
Arce C, Perez-Plasencia C, Gonzalez-Fierro A, de la Cruz-Hernandez E, Revilla-Vazquez A, Chavez-Blanco A, Trejo-Becerril C, Perez-Cardenas E, Taja-Chayeb L, Bargallo E, Villarreal P, Ramirez T, Vela T, Candelaria M, Camargo MF, Robles E, Duenas-Gonzalez A. A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One. 2006 Dec 20;1(1):e98. doi: 10.1371/journal.pone.0000098.
Results Reference
derived
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Hydralazine and Valproate Added to Chemotherapy for Breast Cancer
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