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

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ClinicalTrials.gov Identifier: NCT02950259
Recruitment Status : Active, not recruiting
First Posted : November 1, 2016
Last Update Posted : May 15, 2018
Sponsor:
Collaborator:
IRX Therapeutics
Information provided by (Responsible Party):
Providence Health & Services

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
Breast Neoplasm Breast Neoplasm, Male Triple Negative Breast Cancer Drug: Cyclophosphamide Drug: Indomethacin Drug: Omeprazole Dietary Supplement: Multivitamin 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 Type : Interventional  (Clinical Trial)
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 : February 9, 2017
Actual Primary Completion Date : April 26, 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: Cytoxan

Drug: Indomethacin
Indomethacin 25 mg three times a day for 21 days
Other Name: Indocin

Drug: Omeprazole
One tablet of omeprazole daily for 21 days
Other Name: Prilosec

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

Drug: Indomethacin
Indomethacin 25 mg three times a day for 21 days
Other Name: Indocin

Drug: Omeprazole
One tablet of omeprazole daily for 21 days
Other Name: Prilosec

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




Primary Outcome Measures :
  1. Surgical Delays [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 1 to 26 ]
    Changes in abundance of T-regulatory cells, activated T-cells, myeloid lineages and dendritic cells

  3. Intratumoral T-cell response [ Time Frame: Day 1-26 ]
    change in T-cell clonal responses by T-cell receptor DNA deep sequencing

  4. Intratumoral Immune Response [ Time Frame: Day 1-26 ]
    Characterization of intratumoral immune responses by RNA expression using the Nanostring PanCancer Immune panel and/or Prosigna tumor recurrence score



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02950259


Locations
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Sponsors and Collaborators
Providence Health & Services
IRX Therapeutics
Investigators
Principal Investigator: David Page, MD Providence Health & Services

Additional Information:
Responsible Party: Providence Health & Services
ClinicalTrials.gov Identifier: NCT02950259     History of Changes
Other Study ID Numbers: 16-126B
IRX-2 2016-B ( Other Identifier: IRX Therapeutics )
First Posted: November 1, 2016    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: 5 years
Access Criteria: IPD will be accessed for data verification purposes only.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Providence Health & Services:
Breast Cancer
Early Stage Breast Cancer
Male breast cancer
IRX-2
Immunotherapy
Triple Negative Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Triple Negative Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Breast Diseases
Skin Diseases
Cyclophosphamide
Indomethacin
Omeprazole
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Gout Suppressants