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

Sponsor
Providence Health & Services (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02950259
Collaborator
Brooklyn ImmunoTherapeutics, LLC (Industry)
16
1
2
70.7
0.2

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib Study to Assess the Safety, Tolerability and Immunologic Activity of Preoperative IRX 2 In Early Stage Breast Cancer
Actual Study Start Date :
Feb 9, 2017
Anticipated Primary Completion Date :
Oct 1, 2022
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. Surgical Delays [Day 1 to Day 26]

      Number of surgeries delayed due to adverse events from the IRX-2 regimen

    Secondary Outcome Measures

    1. Tumor Infiltrating Lymphocytes [Day 26]

      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

    Other Outcome Measures

    1. Characterization of peripheral lymphocytes [Day 1 to Day 26]

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

    2. TIL phenotype [Day 1 to 26]

      Changes in abundance of T-regulatory cells, activated T-cells, myeloid lineages and dendritic cells

    3. Intratumoral T-cell response [Day 1-26]

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

    4. Intratumoral Immune Response [Day 1-26]

      Characterization of intratumoral immune responses by RNA expression using the Nanostring PanCancer Immune panel and/or Prosigna tumor recurrence score

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Providence Portland Medical Center Portland Oregon United States 97213

    Sponsors and Collaborators

    • Providence Health & Services
    • Brooklyn ImmunoTherapeutics, LLC

    Investigators

    • Principal Investigator: David Page, MD, Providence Health & Services

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Providence Health & Services
    ClinicalTrials.gov Identifier:
    NCT02950259
    Other Study ID Numbers:
    • 16-126B
    • IRX-2 2016-B
    First Posted:
    Nov 1, 2016
    Last Update Posted:
    Feb 2, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Providence Health & Services
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 2, 2022