Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Examining Bioactivity of PVSRIPO in Invasive Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03564782
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : October 28, 2019
Sponsor:
Collaborators:
Duke University
United States Department of Defense
Information provided by (Responsible Party):
Istari Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE June 10, 2018
First Posted Date  ICMJE June 21, 2018
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE June 30, 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History Complete list of historical versions of study NCT03564782 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Examining Bioactivity of PVSRIPO in Invasive Breast Cancer
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE 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  ICMJE Invasive Breast Cancer
Intervention  ICMJE 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  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 19, 2018)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Women
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shelley Hwang, MD, MPH 919-660-1278 shelley.hwang@duke.edu
Contact: Caroline Morales caroline.morales@duke.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03564782
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Istari Oncology, Inc.
Study Sponsor  ICMJE Istari Oncology, Inc.
Collaborators  ICMJE
  • Duke University
  • United States Department of Defense
Investigators  ICMJE
Study Director: Darell Bigner, MD, PhD Istari Oncology, Inc.
PRS Account Istari Oncology, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP