Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Analgesics

Reproductive Control Agents

Gastrointestinal Agents

Micronutrients

Cyclophosphamide

Indomethacin

Immunomodulating Agents

Omeprazole

Vitamins

Zinc

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Enzyme Inhibitors

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Tocolytic Agents

Cyclooxygenase Inhibitors

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.

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.

One dose of cyclophosphamide 300 mg/m2 IV infusion

Indomethacin 25 mg three times a day for 21 days

One tablet of omeprazole daily for 21 days

Daily multivitamin containing 15-30 mg of zinc for 21 days.

Multivitamin

David Page, MD

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.

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.

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

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.

Fold change of peripheral lymphocytes including activated T-cells, T-regulatory cells, natural killer (NK) cells, and myeloid cells

Post-IRX mean density of T-regulatory cells, activated T-cells, myeloid lineages and dendritic cells post-IRX within stromal tissue compartments.

Change in T-cell clonal responses by T-cell receptor DNA deep sequencing

The Nanostring PanCancer Immune panel was used to estimate increase in PD-L1 mRNA expression among tumor-bearing FFPE specimens.

The safety of IRX-2 will be determined by any surgical delays associated with administration of the study regimen.

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

Brooklyn ImmunoTherapeutics, LLC

Providence Health & Services

Adverse event monitoring/recording happened at set time intervals as per study protocol

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.

Cyclophosphamide: One dose of cyclophosphamide 300 mg/m2 IV infusion

Indomethacin: Indomethacin 25 mg three times a day for 21 days

Omeprazole: One tablet of omeprazole daily for 21 days

Multivitamin: Daily multivitamin containing 15-30 mg of zinc for 21 days.

IRX-2 Regimen -Early Stage 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.

Cyclophosphamide: One dose of cyclophosphamide 300 mg/m2 IV infusion

Indomethacin: Indomethacin 25 mg three times a day for 21 days

Omeprazole: One tablet of omeprazole daily for 21 days

Multivitamin: Daily multivitamin containing 15-30 mg of zinc for 21 days.

IRX-2 Regimen -Triple Negative Breast Cancer

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Menstrual Status

Family History of Breast/Ovarian Cancer

Known BRCA 1/2 Mutation

Due to poor accrual, site opted against enrolling patients into cohort B in favor of a different trial which is ongoing.

Dr. David B. Page

No patients were enrolled into Arm B due to poor accrual and opted against Arm B in favor of the NeoIRX trial.

Establish the Safety of the IRX-2 Regimen When Administered Pre-operatively in Early Stage Breast Cancer (ESBC) Patients

Due to poor patient accrual we opted against enrolling into Cohort B in favor of the neoIRX trial.

Tumor Infiltrating Lymphocytes

Stroma, Any PD-L1: T-Cell (any type)

Stroma, Any PD-L1: Helper T-Cell

Stroma, Any PD-L1: Cytotoxic T-Cell

Stroma, Any PD-L1: Regulatory T-Cell

Stroma, Any PD-L1: Macrophage

Stroma, PD-L1-positive: T-Cell (any type)

Stroma, PD-L1-positive: Helper T-Cell

Stroma, PD-L1-positive: Cytotoxic T-Cell

Stroma, PD-L1-positive: Regulatory T-cell

Stroma, PD-L1-positive: Macrophage

Tumor, Any PD-L1: T-Cell (any type)

Tumor, Any PD-L1: Helper T-Cell

Tumor, Any PD-L1: Cytotoxic T-Cell

Tumor, Any PD-L1: Regulatory T-Cell

Tumor, Any PD-L1: Macrophage

Tumor, PD-L1-positive: T-Cell (any type)

Tumor, PD-L1-positive: Helper T-cell

Tumor, PD-L1-positive: Cytotoxic T-Cell

Tumor, PD-L1-positive: Regulatory T-Cell

Tumor, PD-L1-positive: Macrophage

Stoma and tumor, PD-L1-positive: PD-L1+ IC^3

Due to poor accrual we opted against enrolling in Cohort B in favor of the neoIRX trial.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Pre-operative IRX-2 in Early Stage Breast Cancer (ESBC)	NCT02950259	Breast Neoplasm Breast Neoplasm... Triple Negative...	Cyclophosphamid... Indomethacin Omeprazole Multivitamin	-	Providence Health & Services
Pre-operative IRX-2 in Early Stage Breast Cancer (ESBC)	NCT02950259	Breast Neoplasm Breast Neoplasm... Triple Negative...	Cyclophosphamid... Indomethacin Omeprazole Multivitamin	-	Providence Health & Services

Spots Global Cancer Trial Database for breast neoplasm, male