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 : July 4, 2019
|Condition or disease||Intervention/treatment||Phase|
|Triple Negative Breast Cancer||Biological: PVSRIPO||Early Phase 1|
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.
|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|
|Actual Study Start Date :||June 30, 2019|
|Estimated Primary Completion Date :||July 2021|
|Estimated Study Completion Date :||December 2021|
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.
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.
- 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).
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
|Contact: Shelley Hwang, MD, MPHfirstname.lastname@example.org|
|Contact: Caroline Moralesemail@example.com|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: Shelley Hwang, MD, MPH 919-660-1278 firstname.lastname@example.org|
|Contact: Caroline Morales email@example.com|
|Study Director:||Darell Bigner, MD, PhD||Istari Oncology, Inc.|