Clinical Trials /

Examining Bioactivity of PVSRIPO in Triple Negative Breast Cancer

NCT03564782

Description:

This is a pilot study to examine PVSRIPO bioactivity in tumor tissue after intratumoral administration of PVSRIPO in women with triple negative breast cancer (TNBC).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Examining Bioactivity of PVSRIPO in Triple Negative Breast Cancer
  • Official Title: Examining Oncolytic Poliovirus Bioactivity in Tumor Tissue After Intratumoral Administration of PVSRIPO in Women With Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: Pro00085352
  • SECONDARY ID: W81XWH-16-1-0354
  • NCT ID: NCT03564782

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
PVSRIPOPVSRIPO

Purpose

This is a pilot study to examine PVSRIPO bioactivity in tumor tissue after intratumoral administration of PVSRIPO in women with triple negative breast cancer (TNBC).

Detailed Description

      The study drug PVSRIPO is the live attenuated, oral (Sabin) serotype 1 poliovirus vaccine
      containing a heterologous internal ribosomal entry site (IRES) derived from the human
      rhinovirus type 2 (HRV2). The purpose of this pilot study is to examine PVSRIPO bioactivity
      in tumor tissue after intratumoral administration of PVSRIPO in women with triple negative
      breast cancer (TNBC). The hypothesis is that administration of PVSRIPO in the tumor causes
      inflammation, which stimulates innate and adaptive immune activation in TNBC. Enrollment
      target will include six women with TNBC. Women with stage II-IV ER/PR/HER2 negative (triple
      negative) breast cancer with at least 1 cm of residual tumor after chemotherapy and scheduled
      for standard of care surgery will be eligible.

      The objective of the study is to investigate PVSRIPO-mediated inflammation and immunity in
      women TNBC. The primary exploratory objective is to describe the change in the amount of
      tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO by H&E
      (Haemotoxylin and Eosin).

      Other exploratory objectives are: 1.) to examine tumor tissue pre- and post-injection of
      PVSRIPO for inflammatory and immune signature using arrays, CD155 expression by
      immunohistochemistry (IHC), immune cell infiltrate by IHC and tumor infiltrating immune cells
      using flow cytometry (post-injection only); and 2) To examine blood for inflammatory and
      immune signature using arrays, immune cell composition (antigen presenting cells, B cells and
      T cells), T cell activation by flow cytometry and B cell activation by ELISA and peptide
      arrays. Blood will be collected on day -7 (before polio vaccine booster), day 0 (before
      PVSRIPO injection), day 2 (after PVSRIPO), day 14 (after PVSRIPO before surgery), and in
      follow-up at months 1 and 6 post-PVSRIPO.
    

Trial Arms

NameTypeDescriptionInterventions
PVSRIPOExperimentalPolio vaccine booster will be administered 1 week prior to PVSRIPO injection. On the day of PVSRIPO injection (Day 0), a pre-treatment biopsy is obtained. PVSRIPO in injected into the tumor mass at a dose of 1x10^8 TCID50. On day 14, women will undergo standard-of-care surgical resection of PVSRIPO-treated tumor.

    Eligibility Criteria

            This pilot study will include women with stage II-IV ER/PR/HER2 negative (triple negative)
            breast cancer scheduled to undergo surgical resection.
    
            Inclusion Criteria:
    
              -  Age ≥ 18 years
    
              -  Confirmation of TNBC defined as follows: triple-negative receptor status is defined as
                 estrogen receptor expression ≤ 10%, progesterone receptor expression ≤ 10%, and
                 HER2/Neu expression by IHC 0 or 1+, or 2+ with fluorescence in situ hybridization
                 confirming no amplification of HER2 on a pretreatment tumor sample and prior to
                 initiation of chemotherapy if chemotherapy is planned.
    
              -  Stage II-III TNBC with ≥ 1 cm of residual tumor based on MRI, mammogram, ultrasound,
                 or breast clinical exam as SOC after completion of neoadjuvant chemotherapy, OR Stage
                 IV TNBC with ≥ 1 cm locally recurrent disease (i.e. chest wall recurrence only)
    
              -  ECOG ≤ 1
    
              -  Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/µl, platelets ≥ 125,000 cells/µl
    
              -  Women must have had last dose of chemotherapy at least 3 weeks prior to treatment with
                 PVSRIPO
    
              -  Women must have at least 2 weeks minimum (ideal 3-4 weeks) of a wash-out period after
                 any steroid administration (IV, PO, or intraocular)
    
              -  Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times ULN (upper limit of
                 normal)
    
              -  Women must provide written informed consent prior to enrollment on study
    
              -  Women of childbearing potential will have a negative serum pregnancy test at screening
    
              -  Women of childbearing potential must be willing to avoid pregnancy for the course of
                 the study through 120 days after PVSRIPO injection
    
              -  Surgical resection of the tumor is planned and patient is willing to undergo surgical
                 resection of the cancer
    
            Exclusion Criteria:
    
              -  Stage I TNBC
    
              -  Breast cancer with skin necrosis
    
              -  Concurrent immune therapy, chemotherapy, or steroid therapy
    
              -  Is currently participating in or has participated in a study of an investigational
                 agent or using an investigational device within 4 weeks prior to polio vaccine booster
    
              -  Has a known diagnosis of immunodeficiency
    
              -  Has a known additional malignancy that is progressing or requires active treatment
    
              -  Has known active central nervous system metastases and/or carcinomatous meningitis
    
              -  Has an active autoimmune disease requiring systemic treatment within the past 3 months
                 or a documented history of clinically severe autoimmune disease or a syndrome that
                 requires systemic steroids or immunosuppressive agents
    
              -  Has an active infection requiring systemic therapy
    
              -  Has known psychiatric or substance abuse disorders that would interfere with the
                 requirements of the trial
    
              -  Is pregnant, breastfeeding, or expecting to conceive children within the projected
                 duration of the trial, starting with the screening visit through 120 days after trial
                 treatment
    
              -  Has received prior therapy with an anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CD137, or
                 anti-CTLA-4 (or any other antibody or drug specifically targeting T cell
                 co-stimulation or checkpoint pathways)
    
              -  Has a known history of Human Immunodeficiency Virus (HIV)
    
              -  Has known active Hepatitis B or Hepatitis C
    
              -  Active liver disease with elevated transaminases > 2x ULN
    
              -  Has received a live vaccine within 30 days prior to PVSRIPO treatment
    
                   -  Inactivated vaccines are acceptable and are not an exclusion criterion
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Change in tumor infiltrating immune cells
    Time Frame:10-20 days post-Injection of PVSRIPO
    Safety Issue:
    Description:To describe the change in the amount of tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO by H&E (Haemotoxylin and Eosin).

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Istari Oncology, Inc.

    Trial Keywords

    • PVSRIPO
    • Triple Negative Breast Cancer

    Last Updated