Pre-operative IRX-2 in Early Stage Breast Cancer (ESBC)

Study Overview
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Brief Summary
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The goal of this study is assess the safety and tolerability of the IRX-2 regimen in patients with early stage breast cancer (ESBC) and to estimate the pathologic complete response rate to neoadjuvant anthracycline-based and non-platinum containing chemotherapy in patients with triple-negative breast cancer who have received the IRX-2 Regimen before chemotherapy.

Detailed Description
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This will be a Phase Ib study conducted to determine the safety and tolerability of an IRX-2 regimen in ESBC, to be administered pre-operatively before standard-of-care surgical resection and following standard-of-care diagnostic biopsy. This study will also include triple-negative breast cancer patients who will receive the IRX-2 regimen prior to chemotherapy. Eligible subjects will have early stage breast cancer of any receptor sub-type, for which standard-of-care surgical resection is planned. To be eligible, a minimum of 1 core of tumor-bearing biopsy material must be available for research analysis. Cohort B will enroll subjects triple negative breast cancer (defined by ER<10%, PR<10%, and HER2-negative by NCCN guidelines), T1c+ tumors for which neoadjuvant anthracycline-based and non-platinum containing chemotherapy is planned. The IRX-2 regimen will be administered and completed preceding chemotherapy. Cohort B subjects must undergo post-IRX-2 Regimen biopsy (2-3 cores), followed by commencement of chemotherapy preferably within one week after biopsy. The IRX-2 regimen will be administered in all enrolled subjects. IRX 2 will be administered by subcutaneous injection into the periareolar skin of the affected breast.

Official Title
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A Phase Ib Study to Assess the Safety, Tolerability and Immunologic Activity of Preoperative IRX 2 In Early Stage Breast Cancer

Conditions
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Breast Neoplasm, Breast Neoplasm, Male, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Indomethacin
* Drug: Omeprazole
* Dietary Supplement: Multivitamin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Invasive breast cancer of any receptor subtype diagnosed by core-needle biopsy To undergo surgical resection with curative intent by partial mastectomy (lumpectomy) or mastectomy or Triple negative breast cancer (defined by ER<10%, PR<10%, and HER2-negative by NCCN guidelines), T1c+ tumors for which neoadjuvant anthracycline-based and non-platinum containing chemotherapy is planned Tumor >5 mm in maximum diameter by ultrasound or mammography. (Subjects with smaller tumors may be included at the discretion of the Principal Investigator.) Willing and able to provide written informed consent, including consent for use of available tissue and required blood draws for research purposes Availability of at least one tumor-bearing core specimen from the breast cancer diagnostic biopsy Karnofsky Performance status (KPS) 70% or greater. Female or male ≥18 years of age on day of signing informed consent. Adequate organ function as defined by protocol specified lab results Exclusion Criteria: Prior neoadjuvant systemic therapy is planned Prior surgery, radiotherapy or chemotherapy for this cancer (other than core-needle biopsy) Received an investigational agent within 4 weeks of the first dose of treatment. Diagnosis of immunodeficiency or has received more than replacement doses of corticosteroids any other immunosuppressive therapy within 4 weeks of the first dose of treatment Hypersensitivity to IRX 2, cyclophosphamide, indomethacin, aspirin or ciprofloxacin. Chronic anticoagulation, not including aspirin, but including heparins, warfarin, oral anticoagulants or other platelet function inhibitors, that cannot, in the documented opinion of the investigator, safely be interrupted from at least 2 days prior to the initiation of the study regimen until after surgical resection of the tumor. Another malignancy that required active treatment within 6 months of the first dose of treatment History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, such that trial participation is not in the best interest of the subject, including but not limited to uncontrolled hypertension or clinically significant cardiovascular disease, myocardial infarction within the previous 3 months, active infection or pneumonitis or other pulmonary disease requiring systemic therapy, clinically significant gastritis or peptic ulcer disease (that would preclude the use of indomethacin), stroke of other symptoms of cerebral vascular insufficient within the last 3 months, autoimmune disease that has required systemic treatment within the past 2 years (other than hormone replacement doses), or uncontrolled psychiatric or substance abuse disorders. Pregnancy or lactation. Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IRX-2 Regimen -Early Stage Breast Cancer<br>Enrolled subjects with early stage breast cancer will receive a single dose of cyclophosphamide (300 mg/m2) by IV infusion on Day 1. Also starting on Day 1 and continuing until Day 21, subjects will take daily oral indomethacin (25 mg three times each day), daily oral omeprazole (one tablet) and daily oral multivitamin containing 15-30 mg of zinc. On any 10 consecutive day period between Days 4-17, patients will receive two 1 mL subcutaneous periareolar injections of IRX-2. | Drug: Cyclophosphamide<br>* One dose of cyclophosphamide 300 mg/m2 IV infusion<br>* Other names: Cytoxan;Drug: Indomethacin<br>* Indomethacin 25 mg three times a day for 21 days<br>* Other names: Indocin;Drug: Omeprazole<br>* One tablet of omeprazole daily for 21 days<br>* Other names: Prilosec;Dietary Supplement: Multivitamin<br>* Daily multivitamin containing 15-30 mg of zinc for 21 days.<br>* Other names: Vitamin;|
| Experimental: IRX-2 Regimen -Triple Negative Breast Cancer<br>Enrolled subjects with triple negative breast cancer will receive a single dose of cyclophosphamide (300 mg/m2) by IV infusion on Day 1. Also starting on Day 1 and continuing until Day 21, subjects will take daily oral indomethacin (25 mg three times each day), daily oral omeprazole (one tablet) and daily oral multivitamin containing 15-30 mg of zinc. On any 10 consecutive day period between Days 4-17, patients will receive two 1 mL subcutaneous periareolar injections of IRX-2. | Drug: Cyclophosphamide<br>* One dose of cyclophosphamide 300 mg/m2 IV infusion<br>* Other names: Cytoxan;Drug: Indomethacin<br>* Indomethacin 25 mg three times a day for 21 days<br>* Other names: Indocin;Drug: Omeprazole<br>* One tablet of omeprazole daily for 21 days<br>* Other names: Prilosec;Dietary Supplement: Multivitamin<br>* Daily multivitamin containing 15-30 mg of zinc for 21 days.<br>* Other names: Vitamin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical Delays | Number of surgeries delayed due to adverse events from the IRX-2 regimen | Day 1 to Day 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Infiltrating Lymphocytes | Change in tumor infiltrating lymphocyte (TIL) score as measured by H&E TIL count according to Salgado criteria from pre-surgical biopsy to resected tumor specimen | Day 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IRX-2, Breast Cancer, Early Stage Breast Cancer, Male breast cancer, Immunotherapy, Triple Negative Breast Cancer