Examining Bioactivity of PVSRIPO in Invasive Breast Cancer

NCT03564782 | Completed Early Phase 1 Results FDA Drug

• 2 other identifiers: Pro00085352W81XWH-16-1-0354
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Invasive Breast Cancer

Keywords

PVSRIPO; Invasive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Change in Tumor Infiltrating Immune Cells

  To describe the change in the amount of tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO

  10-20 days post-Injection of PVSRIPO

Study Arms (1)

PVSRIPO

EXPERIMENTAL

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

Interventions

PVSRIPO BIOLOGICAL

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.

PVSRIPO

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istari Oncology, Inc.: lead
• Duke University: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Results Point of Contact

• Title: W. Garrett Nichols, MD MS
• Organization: Istari Oncology

info@istarioncology.com

919-245-7662

Study Officials

• Darell Bigner, MD, PhD

  Istari Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 10, 2018
• First Posted: June 21, 2018
• Study Start: June 30, 2019
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: February 8, 2024
• Results First Posted: February 8, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)