Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

NCT ID: NCT01292083

Last Updated: 2014-02-06

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-03-31

Brief Summary

This clinical trial studies azacitidine in treating patients with triple negative stage I-IV invasive breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the ability of deoxyribonucleic acid (DNA) methylation inhibition using 5-azacitidine to induce expression of the estrogen receptor (ER) and progesterone receptor (PR) genes in solid human triple negative invasive breast cancer. SECONDARY OBJECTIVES: I. To determine the effect of systemic 5-azacitidine therapy on the expression of other methylated genes in triple negative invasive breast cancer using an Illumina GoldenGate array. OUTLINE: Patients receive azacitidine intravenously (IV) over 10-40 minutes 5 days a week for 2 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo definitive breast surgery within 12 days of the last dose of azacitidine.

Conditions

Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

See Detailed Description

Group Type: EXPERIMENTAL

azacitidine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

immunohistochemistry staining method

Intervention Type: OTHER

Correlative studies

polymerase chain reaction

Intervention Type: GENETIC

Correlative studies

western blotting

Intervention Type: GENETIC

Correlative studies

nucleic acid sequencing

Intervention Type: GENETIC

Correlative studies

therapeutic conventional surgery

Intervention Type: PROCEDURE

Undergo definitive breast surgery

Interventions

azacitidine

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

immunohistochemistry staining method

Correlative studies

Intervention Type: OTHER

polymerase chain reaction

Correlative studies

Intervention Type: GENETIC

western blotting

Correlative studies

Intervention Type: GENETIC

nucleic acid sequencing

Correlative studies

Intervention Type: GENETIC

therapeutic conventional surgery

Undergo definitive breast surgery

Intervention Type: PROCEDURE

Other Intervention Names

5-AC; 5-azacytidine; azacytidine; Vidaza; immunohistochemistry; PCR; Blotting, Western; Western Blot; Gene Sequencing; Molecular Biology, Nucleic Acid Sequencing

Eligibility Criteria

Inclusion Criteria

• Resectable tumor measuring 2 cm or more
• Histologically documented triple negative invasive breast cancer characterized by 0% Immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for PR-alpha, and no amplification of HER2/neu by fluorescence in situ hybridization (FISH); standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and PR-beta
• Southwest Oncology Group (SWOG) performance status of less than or equal to 1
• Absolute neutrophil count (ANC) >= 1500/μL
• Hemoglobin (Hgb) >= 9 g/dL
• Platelets >= 100,000/uL
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x upper limit normal (ULN) or =< 5.0 x ULN in patients with liver metastases
• Creatinine =< 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min
• Albumin >= 3 g/dL
• Potassium >= lower limit normal (LLN)
• Phosphorous >= LLN
• Calcium >= LLN
• Magnesium > LLN
• Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment
• Accessible for treatment and follow-up
• Written informed consent prior to study entry

Exclusion Criteria

• HER2/neu amplification by FISH
• Concurrent neoadjuvant treatment with chemotherapy, endocrine therapy, or radiotherapy
• Known hypersensitivity to azacitidine or mannitol
• Preexisting hepatic impairment or renal impairment
• Intent to receive additional neoadjuvant therapy prior to surgery
• Concurrent use of an histone deacetylase (HDAC) inhibitor or hydralazine
• Known diagnosis of human immunodeficiency virus (HIV) infection
• Major surgery < 4 weeks prior to starting study drug
• Pregnant or breastfeeding or female of reproductive potential not using an effective method of birth control
• Other concurrent severe, uncontrolled infection or intercurrent illness, including but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase inhibitors) within 6 months of study entry
• Underlying medical, psychiatric or social conditions that would preclude patient from receiving treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Agustin Garcia, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Other Identifiers

NCI-2011-00117

Identifier Type: REGISTRY

Identifier Source: secondary_id

1B-09-15

Identifier Type: -

Identifier Source: org_study_id