Breast Cancer InvasivePhase 2BRE-04NCT04891068
BRE-04: Window of Opportunity Trial of Preoperative Low Dose Azacitidine in High-Risk Early Stage Breast Cancer
A Phase 2 study testing Azacitidine in people with Breast Cancer Invasive and Early-stage Breast Cancer, run by University of Illinois Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer Invasive, Early-stage Breast Cancer, High Risk Breast Carcinoma
- What is being tested?
- Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Jan 2022to May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years of age at time of consent
- ECOG 0, 1, or 2
- Histologically confirmed invasive breast carcinoma documented by biopsy. AJCC 8th edition clinical stage T1a-T3/N0-N1/M0 by physical exam or radiologic studies
- 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
- ER positive (as determined by immunohistochemistry (IHC)) and any of the following high risk characteristics:
Show all 13Show fewer
- HER2 positive (IHC or FISH)
- Node positive
- Any clinical high-risk expression profile (mammaprint, oncotype, endopredict)
- 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.
- Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required per institutional practice guidelines.
- 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.
Who cannot join
- 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.
- Any type of breast implants
- Active infection requiring systemic therapy
- Uncontrolled HIV/AIDS or active viral hepatitis
- Pregnant or nursing
- 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.
- 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.
- Other major comorbidity, as determined by study PI
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Illinois Cancer Center
Chicago, Illinois, 60612
VK Gadi, MD, 312-996-1581, vkgadi@uic.edu
Meredith Russell, 312-355-5112, mrussel3@uic.edu
About this study
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.
Read the 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
- Being tested
- Azacitidine
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza
5-Azacitidine is a pyrimidine nucleoside analog in which nitrogen replaces carbon at position 5
| Study group | Role | What they receive |
|---|---|---|
| Single arm with previously untreated high risk early stage breast cancer | Experimental | All participants will receive azacitidine 50mg/m2 SC daily for five consecutive days. Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 weeks from first dose of azacitidine
Secondary outcomes (5)
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
Measured: 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
Measured: 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
Measured: 30 days after last dose of azacitidine
Disease Free Survival (DFS)
Number of days participants had DFS
Measured: 2 years
Overall Survival (OS)
Number of days participants had OS
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2021
- Study start10 Jan 2022
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer InvasiveStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, window of opportunity trial in which patient with previously untreated high risk early stage breast cancer will receive 5 consecutive days of azacitidine 50mg/m2 SC followed by standard of care therapy
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vijayakrishna Krishnamurthy Gadi, University of Illinois Chicago
- Investigators
- Vijayakrishna Krishnamurthy Gadi, MD, PhD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04891068
- Sponsor's protocol ID
- 2021-0215
- Acronym
- BRE-04
- Status last verified
- Nov 2026
- First submitted
- 11 May 2021
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BRE-04: Window of Opportunity Trial of Preoperative Low Dose Azacitidine in High-Risk Early Stage Breast Cancer
- ClinicalTrials.gov ID
- NCT04891068
- Acronym / sponsor ID
- BRE-04 / 2021-0215
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Study start
- 10 Jan 2022 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 18 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, window of opportunity trial in which patient with previously untreated high risk early stage breast cancer will receive 5 consecutive days of azacitidine 50mg/m2 SC followed by standard of care therapy
| Arm | Type | Receives |
|---|---|---|
| Single arm with previously untreated high risk early stage breast cancer | Experimental | Drug: AzacitidineAll participants will receive azacitidine 50mg/m2 SC daily for five consecutive days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥ 18 years of age at time of consent
- ECOG 0, 1, or 2
- Histologically confirmed invasive breast carcinoma documented by biopsy. AJCC 8th edition clinical stage T1a-T3/N0-N1/M0 by physical exam or radiologic studies
- 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
Key exclusion criteria (8 listed)
- 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.
- Any type of breast implants
- Active infection requiring systemic therapy
- Uncontrolled HIV/AIDS or active viral hepatitis
- Pregnant or nursing
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: Vidaza5-Azacitidine is a pyrimidine nucleoside analog in which nitrogen replaces carbon at position 5 | Drug | Single arm with previously untreated high risk early stage breast cancer |
Primary outcome
Change in tumor infiltrating lymphocytes (TILs) count in primary tumors from patients with high-risk early stage breast cancer following low-dose azacitidine therapy.
Time frame: 2 weeks from first dose of azacitidine
Number of participants that show tumor infiltrating lymphocytes (TILs) in primary tumors from patients with high-risk early stage breast cancer
5 secondary outcomes
Clinical response (change Ki67 and tumor size) of primary tumor following treatment with low dose azacitidine therapy
Time frame: 2 weeks from first dose of azacitidine
Safety - completion rate of low-dose azacitidine
Time frame: 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
Time frame: 30 days after last dose of azacitidine
Disease Free Survival (DFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vijayakrishna Krishnamurthy Gadi, MD, PhD principal investigator
University of Illinois Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine in people with Breast Cancer Invasive and Early-stage Breast Cancer, run by University of Illinois Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact VK Gadi, MD, PhD (312-996-1581, vkgadi@uic.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in tumor infiltrating lymphocytes (TILs) count in primary tumors from patients with high-risk early stage breast cancer following low-dose azacitidine therapy. (time frame: 2 weeks from first dose of azacitidine). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.