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

• Status: Recruiting
• Trial end date: 2023-05-01
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Illinois at Chicago
• Treatments: Azacitidine

Criteria

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 T1c-T2/N0-N1/M0 by physical exam or radiologic studies.

4. Primary breast tumor > 1cm

5. 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)

6. 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

7. No evidence of distant metastases (M0 per AJCC staging guidelines)

8. 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.

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

10. 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.

8. Other major comorbidity, as determined by study PI