Clinical Trials /

Examining Bioactivity of PVSRIPO in Invasive Breast Cancer

NCT03564782

Description:

This is a pilot study to examine PVSRIPO bioactivity in tumor tissue after intratumoral administration of PVSRIPO in women with invasive breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

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

Conditions

  • Invasive 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 invasive breast cancer.

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 invasive breast
      cancer. The hypothesis is that administration of PVSRIPO in the tumor causes inflammation,
      which stimulates innate and adaptive immune activation in invasive breast cancer. Enrollment
      target will include six women with invasive breast cancer. Women with stage II-IV invasive
      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 invasive breast cancer. 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.
  • PVSRIPO

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 invasive breast cancer including any of the following:

               -  Triple-negative breast cancer defined as receptor status being 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.

               -  Hormone positive breast cancer defined as receptor status being estrogen receptor
                  expression > 10%, progesterone receptor expression > 10% prior to initiation of
                  chemotherapy.

               -  HER2+ breast cancer defined as HER2/Neu expression by IHC 3+ or fluorescence in
                  situ hybridization confirming amplification of HER2 on a pretreatment tumor
                  sample prior to initiation of chemotherapy. HER2+ and hormone positive (ie triple
                  positive) breast cancers are included in this study.

          -  Stage II-III invasive breast cancer 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 BC 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 ≥ 100,000 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, prior to
             conduct of screening procedures and 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:

          -  T1 N0 invasive breast cancer

          -  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:Recruiting
Lead Sponsor:Istari Oncology, Inc.

Trial Keywords

  • PVSRIPO
  • Invasive Breast Cancer

Last Updated

October 24, 2019