BRE-04: Window of Opportunity Trial of Preoperative Low Dose Azacitidine in High-Risk Early Stage Breast Cancer (BRE-04)

To determine the effect of low dose azacitidine therapy on tumor infiltrating lymphocytes (TILs) in primary tumors from patients with high-risk early stage breast cancer, paired t-tests will be first used to compare TIL count in pre- and post-treatment specimens.

Study Overview

• Status: Recruiting
• Conditions: Early-stage Breast Cancer; Breast Cancer Invasive; High Risk Breast Carcinoma
• Intervention / Treatment: Drug: Azacitidine

Detailed Description

To determine the effect of low dose azacitidine therapy on tumor infiltrating lymphocytes (TILs) in primary tumors from patients with high-risk early stage breast cancer, paired t-tests will be first used to compare TIL count in pre- and post-treatment specimens. Median TIL counts will be compared between the pre- and post-treatment specimens with the Wilcoxon signed-rank test if TIL count does not follow normal distribution. General linear model (GLM) or kruskal wallis test will be used in the multivariate analyses to estimate the effect of low dose azacitidine therapy on TILs after adjusting for other clinical factors and patients characteristics, including the heterogeneity of tumors.

Screening Evaluation Visit All screening procedures will take place within 30 days of the first treatment visit unless otherwise noted.

• Informed consent, HIPAA authorization
• Medical history including prior and concurrent therapies and pathology
• Physical exam, height, weight
• Vital signs (blood pressure, heart rate, temperature)
• Review of concomitant medications
• ECOG performance status
• Blood chemistries (sodium, potassium, serum creatinine [or GFR], calcium, albumin, ALT, AST, total bilirubin, alkaline phosphatase, total protein)
• CBC with differential
• Hepatitis B screening (hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs))
• Diagnostic Mammogram (NOTE: can be performed up to 60 days prior to study enrollment) Tumor and axillary assessment
• Surgical assessment
• Serum pregnancy test for women of childbearing potential (NOTE: serum βhCG within 14 days prior to study registration).
• Archival tumor tissue assessment

Azacitidine Treatment Visits Day 1

• Pre-treated with ondansetron 8mg PO once 30 minutes prior to azacitidine administration.
• Urine pregnancy test for women of childbearing-potential (NOTE: if >7days since screening)
• Research blood draw
• Azacitidine administration
• AE assessment

Days 2-5

• Premedicate with ondansetron 8mg PO once 30 minutes prior to azacitidine administration.

  • Azacitidine administration

Pre study biopsy visit

• Physical exam, weight
• Vital signs (blood pressure, heart rate, temperature)
• Review of concomitant medications
• ECOG performance status
• Blood chemistries (sodium, potassium, serum creatinine [or GFR], calcium, albumin, ALT, AST, total bilirubin, alkaline phosphatase, total protein)
• CBC with differential
• Research blood draw
• AE assessment

Post Study Biopsy Follow-Up visit

• Physical exam, weight
• Vital signs (blood pressure, heart rate, temperature)
• Review of concomitant medications
• ECOG performance status
• Research blood draw
• Archival tumor tissue assessment
• AE assessment

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: VK Gadi, MD, PhD; Phone Number: 312-996-1581; Email: vkgadi@uic.edu
• Study Contact Backup: Name: Michelle Karan, BS; Phone Number: 224-563-7137; Email: makaran2@uic.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
      • Contact: VK Gadi, MD; Phone Number: 312-996-1581; Email: vkgadi@uic.edu
      • Contact: Michelle Karan; Phone Number: 224-563-7137; Email: makaran2@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years of age at time of consent
2. ECOG 0, 1, or 2
3. Histologically confirmed invasive breast carcinoma documented by biopsy. AJCC 8th edition clinical stage T1a-T3/N0-N1/M0 by physical exam or radiologic studies
4. Disease characteristics I. TNBC (Less than or equal to 10% of tumor cells staining for ER and for PR by immunohistochemistry (IHC). HER2-negative, as defined by ASCO/CAP guidelines)

OR

II. ER positive (as determined by immunohistochemistry (IHC)) and any of the following high risk characteristics:

1. HER2 positive (IHC or FISH)
2. Node positive
3. Any clinical high-risk expression profile (mammaprint, oncotype, endopredict)
4. PR negative (IHC) OR III. HER 2 positive (as defined by ASCO/ACP guidelines) f. Demonstrates adequate organ function as defined in table below. All screening labs to be obtained within 30 days prior to registration.

System Laboratory Value Hematological Leukocytes ≥3,000/mm3 Platelet count ≥ 100,000/mm3 Absolute Neutrophil Count (ANC) ≥ 1,500/mm3 Hemoglobin (Hgb) ≥ 9.0 g/dL Renal Creatinine/Calculated creatinine clearance (CrCl) Cr < 1.5 x upper limit of normal (ULN) or CrCl ≥ 50 mL/min using the Cockcroft-Gault formula Hepatic Bilirubin Bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's syndrome may have a bilirubin > 1.5 × ULN, if no evidence of biliary obstruction exists Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN g. No evidence of distant metastases (M0 per AJCC staging guidelines) h. Provided written informed consent and HIPAA authorization for release of personal health information, via an approved UIC Institutional Review Board (IRB) informed consent form and HIPAA authorization.

i. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required per institutional practice guidelines.

j. As determined at the discretion of the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

1. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy, radiotherapy directed towards the primary breast tumor and/or ipsilateral axillary lymph nodes or investigational agents) with therapeutic intent for the current breast cancer.
2. Any type of breast implants
3. Active infection requiring systemic therapy
4. Uncontrolled HIV/AIDS or active viral hepatitis
5. Pregnant or nursing
6. Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of this investigational regimen, as determined by the treating medical oncologist.
7. Any mental or medical condition that prevents the patient from giving informed consent or participating in the trial unless a Legal Authorized Representative (LAR) is in place to sign on behalf of the patient.
8. Other major comorbidity, as determined by study PI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm with previously untreated high risk early stage breast cancer; All participants will receive azacitidine 50mg/m2 SC daily for five consecutive days.	Drug: Azacitidine; 5-Azacitidine is a pyrimidine nucleoside analog in which nitrogen replaces carbon at position 5; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in tumor infiltrating lymphocytes (TILs) count in primary tumors from patients with high-risk early stage breast cancer following low-dose azacitidine therapy.	Number of participants that show tumor infiltrating lymphocytes (TILs) in primary tumors from patients with high-risk early stage breast cancer	2 weeks from first dose of azacitidine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response (change Ki67 and tumor size) of primary tumor following treatment with low dose azacitidine therapy	Number of participants that have a clinical response at time of surgery based on changes in the Ki-67 index	2 weeks from first dose of azacitidine
Safety - completion rate of low-dose azacitidine	Number of participants that fail to complete the planned course of treatment intervention using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5	30 days after last dose of azacitidine
Safety - tolerability of low-dose azacitidine therapy assessed by using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5	Number of participants that have treatment related adverse events using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5	30 days after last dose of azacitidine
Disease Free Survival (DFS)	Number of days participants had DFS	2 years
Overall Survival (OS)	Number of days participants had OS	2 years

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Vijayakrishna Krishnamurthy Gadi, MD, PhD, University of Illinois at Chicago

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 13, 2021
• First Posted (Actual): May 18, 2021

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine
• Other Study ID Numbers: 2021-0215

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No