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

Triple Negative Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02950259
• Other study ID #: 16-126B
• Secondary ID: IRX-2 2016-B
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 9, 2017
• Est. completion date: May 2024

Study information

• Verified date: January 2024
• Source: Providence Health & Services
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 16
• Est. completion date: May 2024
• Est. primary completion date: May 13, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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).

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasm, Male
• Breast Neoplasms
• Breast Neoplasms, Male
• Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• 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

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

Locations

Country	Name	City	State
United States	Providence Portland Medical Center	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
Providence Health & Services	Brooklyn ImmunoTherapeutics, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Intratumoral T-cell Clonality Response	Change in T-cell clonal responses by T-cell receptor DNA deep sequencing	Day 1-26
Other	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
Primary	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	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

External Links

•   Providence Cancer Center