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

Not Applicable

Withdrawn

• Conditions: Recurrent Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Triple-negative Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IA Breast Cancer
• Interventions: Drug: azacitidine; Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Genetic: polymerase chain reaction; Genetic: western blotting; Genetic: nucleic acid sequencing; Procedure: therapeutic conventional surgery

• Registration Number: NCT01292083
• Lead Sponsor: University of Southern California

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.

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-02-02
• Study First Submitted QC: 2011-02-07
• Study First Posted: 2011-02-09
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-05
• Last Update Posted: 2014-02-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	laboratory biomarker analysis	See Detailed Description
Treatment	immunohistochemistry staining method	See Detailed Description
Treatment	polymerase chain reaction	See Detailed Description
Treatment	western blotting	See Detailed Description
Treatment	nucleic acid sequencing	See Detailed Description
Treatment	therapeutic conventional surgery	See Detailed Description
Treatment	azacitidine	See Detailed Description

Primary Outcome Measures

Name	Time	Method
Percent of participants with ER/PR response after receiving 10 doses of 5-Azacitidine	6 months after enrollment of last patient