Examining Bioactivity of PVSRIPO in Invasive Breast Cancer

• ClinicalTrials.gov Identifier: NCT03564782
• Recruitment Status: Recruiting
• First Posted: June 21, 2018
• Last Update Posted: October 28, 2019
• Sponsor: Istari Oncology, Inc.
• Collaborators: Duke University; United States Department of Defense
• Information provided by (Responsible Party): Istari Oncology, Inc.

Tracking Information

• First Submitted Date: June 10, 2018
• First Posted Date: June 21, 2018
• Last Update Posted Date: October 28, 2019
• Actual Study Start Date: June 30, 2019
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2018)

Change in tumor infiltrating immune cells [ Time Frame: 10-20 days post-Injection of PVSRIPO ]

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).

• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03564782 on ClinicalTrials.gov Archive Site
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• Brief Summary: 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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

Intervention Model: Single Group Assignment
Intervention Model Description:

All subjects will receive intratumoral injection of the study drug PVSRIPO at a dose of 1x10^8 TCID50 (tissue culture infectious dose). On Day 14 after injection, subjects will undergo standard-of-care surgical resection of PVSRIPO-treated tumor.

Masking: None (Open Label)
Primary Purpose: Basic Science

• Condition: Invasive Breast Cancer

Intervention

Biological: PVSRIPO

The live, attenuated, oral (Sabin), serotype 1 poliovirus vaccine booster will be administered 1 week before PVSRIPO injection. 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). It will be given at a dose of 1x10^8 TCID50 (tissue culture infectious dose) directly into the breast tumor.

Study Arms

Experimental: PVSRIPO

Polio 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.

Intervention: Biological: PVSRIPO

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 19, 2018): 6
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2021
• Estimated Primary Completion Date: July 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Women

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Shelley Hwang, MD, MPH; 919-660-1278; shelley.hwang@duke.edu

Contact: Caroline Morales; caroline.morales@duke.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03564782
• Other Study ID Numbers: Pro00085352; W81XWH-16-1-0354 ( Other Grant/Funding Number: US Department of Defense (DoD) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Istari Oncology, Inc.
• Study Sponsor: Istari Oncology, Inc.

Collaborators

• Duke University
• United States Department of Defense

Investigators

• Study Director: Darell Bigner, MD, PhD; Istari Oncology, Inc.

• PRS Account: Istari Oncology, Inc.
• Verification Date: October 2019