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

Stage IV Breast Cancer Clinical Trial

Official title:

A Pilot Clinical Trial to Evaluate the Biological Activity of 5-azacitidine on ER and PR Expression in Triple Negative Invasive Breast Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01292083
• Other study ID #: 1B-09-15
• Secondary ID: NCI-2011-00117
• Status: Withdrawn
• Phase: N/A
• First received: February 2, 2011
• Last updated: February 5, 2014
• Start date: January 2011
• Est. completion date: March 2013

Study information

• Verified date: February 2014
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• 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 Neoplasms
• Triple-negative Breast Cancer

Intervention

Drug:
• azacitidine
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• immunohistochemistry staining method
Correlative studies

Genetic:
• polymerase chain reaction
Correlative studies
• western blotting
Correlative studies
• nucleic acid sequencing
Correlative studies

Procedure:
• therapeutic conventional surgery
Undergo definitive breast surgery

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of participants with ER/PR response after receiving 10 doses of 5-Azacitidine		6 months after enrollment of last patient	No