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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Neoplasm; Triple Negative Breast Cancer; Breast Neoplasm, Male
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Indomethacin; Drug: Omeprazole; Dietary supplement: Multivitamin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IRX-2 Regimen -Early Stage Breast Cancer; 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; One dose of cyclophosphamide 300 mg/m2 IV infusion; Other Names: Cytoxan; Drug: Indomethacin; Indomethacin 25 mg three times a day for 21 days; Other Names: Indocin; Drug: Omeprazole; One tablet of omeprazole daily for 21 days; Other Names: Prilosec; Dietary supplement: Multivitamin; Daily multivitamin containing 15-30 mg of zinc for 21 days.; Other Names: Vitamin
Experimental: IRX-2 Regimen -Triple Negative Breast Cancer; 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; One dose of cyclophosphamide 300 mg/m2 IV infusion; Other Names: Cytoxan; Drug: Indomethacin; Indomethacin 25 mg three times a day for 21 days; Other Names: Indocin; Drug: Omeprazole; One tablet of omeprazole daily for 21 days; Other Names: Prilosec; Dietary supplement: Multivitamin; Daily multivitamin containing 15-30 mg of zinc for 21 days.; Other Names: Vitamin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the Safety of the IRX-2 Regimen When Administered Pre-operatively in Early Stage Breast Cancer (ESBC) Patients	The safety of IRX-2 will be determined by any surgical delays associated with administration of the study 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 hematoxylin and eosin tumor infiltrating lymphocytes (H&E TIL) count according to Salgado criteria from pre-surgical biopsy to resected tumor specimen	At time of pre-surgical biopsy and time of tumor specimen resection at day 26

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of Peripheral Lymphocytes	Fold change of peripheral lymphocytes including activated T-cells, T-regulatory cells, natural killer (NK) cells, and myeloid cells	Day 1 to Day 26
TIL Phenotype	Post-IRX mean density of T-regulatory cells, activated T-cells, myeloid lineages and dendritic cells post-IRX within stromal tissue compartments.	Day 1 to 26
Intratumoral T-cell Clonality Response	Change in T-cell clonal responses by T-cell receptor DNA deep sequencing	Day 1-26
Intratumoral Immune Response	The Nanostring PanCancer Immune panel was used to estimate increase in PD-L1 mRNA expression among tumor-bearing FFPE specimens.	Day 1-26

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Brooklyn ImmunoTherapeutics, LLC
• Investigators: Principal Investigator: David Page, MD, Providence Health & Services

Publications and helpful links

General Publications

• Sanchez K, Kim I, Chun B, Pucilowska J, Redmond WL, Urba WJ, Martel M, Wu Y, Campbell M, Sun Z, Grunkemeier G, Chang SC, Bernard B, Page DB. Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer. Breast Cancer Res. 2021 Jan 7;23(1):2. doi: 10.1186/s13058-020-01378-4.

Helpful Links

• Providence Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2017
• Primary Completion (Actual): May 13, 2019
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: October 28, 2016
• First Submitted That Met QC Criteria: October 28, 2016
• First Posted (Estimated): November 1, 2016

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Breast Cancer; Immunotherapy; Early Stage Breast Cancer; Triple Negative Breast Cancer; Male breast cancer; IRX-2
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Reproductive Control Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Gout Suppressants; Tocolytic Agents; Cyclophosphamide; Indomethacin; Omeprazole
• Other Study ID Numbers: 16-126B; IRX-2 2016-B (Other Identifier: IRX Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Providence Health & Services has agreed to allow IRX Therapeutics to have access PHI for auditing purposes. Any non-Providence Health & Services employee who will access PHI will be required to sign a confidentiality agreement and will not be permitted to remove PHI from Providence Health & Services.
• IPD Sharing Time Frame: 5 years
• IPD Sharing Access Criteria: IPD will be accessed for data verification purposes only.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No