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Examining Bioactivity of PVSRIPO in Triple Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT03564782
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
Duke University
United States Department of Defense
Information provided by (Responsible Party):
Istari Oncology, Inc.

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Triple Negative Breast Cancer Biological: PVSRIPO Early Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
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
Official Title: Examining Oncolytic Poliovirus Bioactivity in Tumor Tissue After Intratumoral Administration of PVSRIPO in Women With Triple Negative Breast Cancer
Estimated Study Start Date : April 15, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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.
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.




Primary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women
Accepts Healthy Volunteers:   No
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

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): NCT03564782


Contacts
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Contact: Shelley Hwang, MD, MPH 919-660-1278 shelley.hwang@duke.edu
Contact: Laura Gorski 919-660-1278 laura.gorski@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Shelley Hwang, MD, MPH    919-660-1278    shelley.hwang@duke.edu   
Contact: Laura Gorski    919-660-1278    laura.gorski@duke.edu   
Sponsors and Collaborators
Istari Oncology, Inc.
Duke University
United States Department of Defense
Investigators
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Study Director: Darell Bigner, MD, PhD Istari Oncology, Inc.

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Responsible Party: Istari Oncology, Inc.
ClinicalTrials.gov Identifier: NCT03564782     History of Changes
Other Study ID Numbers: Pro00085352
W81XWH-16-1-0354 ( Other Grant/Funding Number: US Department of Defense (DoD) )
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Istari Oncology, Inc.:
PVSRIPO
Triple Negative Breast Cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases