Preoperative low dose azacitidine for high-risk early stage breast cancer

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

This study is testing if a low dose of azacitidine can boost the immune response in patients with high-risk early stage breast cancer before they have surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Illinois at Chicago (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Chicago, Illinois)
• Trial ID: NCT04891068 on ClinicalTrials.gov

What this trial studies

This trial investigates the effects of low dose azacitidine on tumor infiltrating lymphocytes (TILs) in patients with high-risk early stage breast cancer. Participants will undergo treatment with azacitidine before surgery, and their tumor samples will be analyzed to compare TIL counts before and after treatment. Statistical methods, including paired t-tests and Wilcoxon signed-rank tests, will be employed to assess the impact of the therapy on TIL levels. The study aims to better understand how azacitidine may enhance immune response in breast cancer patients.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 and older with histologically confirmed invasive breast carcinoma and specific high-risk characteristics.

Not a fit: Patients with low-risk breast cancer or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve immune response against tumors in high-risk breast cancer patients.

How similar studies have performed: While this approach is novel, similar studies exploring immune modulation in cancer treatment have shown promising results.

Eligibility 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 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

Where this trial is running

Chicago, Illinois

• University of Illinois Cancer Center — Chicago, Illinois, United States (Recruiting)

Study contacts

• Principal investigator: Vijayakrishna Krishnamurthy Gadi, MD, PhD — University of Illinois at Chicago
• Study coordinator: VK Gadi, MD, PhD

Conditions Breast Cancer Invasive; Early-stage Breast Cancer; High Risk Breast Carcinoma