PVSRIPO in Recurrent Malignant Glioma

A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients

This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

Study Overview

• Status: Active, not recruiting
• Conditions: Malignant Glioma
• Intervention / Treatment: Biological: PVSRIPO

Detailed Description

This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of this study is to investigate the safety and efficacy (anti-tumor response and survival) of PVSRIPO in recurrent WHO grade IV malignant glioma.

Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.

• Study Type: Interventional
• Enrollment (Estimated): 122
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94941
      • UCSF Neurological Surgery
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Preston Robert Tisch Brain Tumor Center at Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA SUMMARY:

1. Patients must have a recurrent (first or second recurrence only, including this recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma will be considered a first recurrence) supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (a minimum measurement of 1 cm and maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate.
2. Male patients who are sexually active are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. Female subjects are eligible if he and/or his partner(s) meets the criteria outlined in the protocol.
3. Age ≥ 18 years of age.
4. Karnofsky Performance Status (KPS) Score ≥ 70%.
5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.
7. Neutrophil count ≥ 1000 prior to biopsy.
8. Hemoglobin ≥ 9 prior to biopsy.
9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
10. Creatinine ≤ 1.2 x normal range prior to biopsy.
11. Positive serum anti-PV titer prior to biopsy.
12. The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of the study agent.
13. At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
14. A signed IRB-approve informed consent form (ICF).
15. Able to undergo brain MRI with and without contrast.

EXCLUSION CRITERIA SUMMARY:

1. Females who are pregnant or breast-feeding.
2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, their designate, and the reviewer designated by the sponsor.
3. Patients with severe, active co-morbidity, defined as in the protocol.
4. Patients with a previous history of neurological complications due to PV infection.
5. Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used.
6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1 week)] prior to starting the study drug.
7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.
8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation.
9. Prior to enrollment, has not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.
10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of multiple areas of active (growing) disease (active multifocal disease); tumors with contrast-enhancing tumor component crossing the midline (crossing the corpus callosum); extensive subependymal disease (tumor touching subependymal space is allowed); or extensive leptomeningeal disease (tumor touching leptomeninges is allowed).
11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).
12. Patients with known history of agammaglobulinemia.
13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for PVSRIPO infusion.
14. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
15. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine.
17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polio/Rhinovirus Recombinant (PVSRIPO)	Biological: PVSRIPO; A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Radiographic Response Rate	Assess objective anti-tumor response based on iRANO criteria.	24 months after initial PVSRIPO infusion and through study completion.
Objective Radiographic Response Rate	Assess objective anti-tumor response based on iRANO criteria.	36 months after initial PVSRIPO infusion and through study completion.
Duration of Objective Radiographic Response	Assess time of confirmed response to confirmed progressive disease/death.	24 months after initial PVSRIPO infusion and through study completion.
Duration of Objective Radiographic Response	Assess time of confirmed response to confirmed progressive disease/death.	36 months after initial PVSRIPO infusion and through study completion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival, relative to external control group(s)	24 and 36 months after initial PVSRIPO infusion and through study completion.
Landmark Survival	Overall survival at 24 and 36 months and greater	24 and 36 months post-infusion and through study completion.
Disease Control Rate Following PVSRIPO Infusion	The percentage of patients classified as non-progressive by radiographic response based on standard criteria.	24 and 36 months after initial PVSRIPO infusion and through study completion.
Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs	Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.	While on study; average of 12 to 36 months after initial PVSRIPO infusion.

Collaborators and Investigators

• Sponsor: Istari Oncology, Inc.
• Collaborators: Duke University
• Investigators: Principal Investigator: Dina Randazzo, DO, Duke University

Publications and helpful links

Helpful Links

• The Preston Robert Tisch Brain Tumor Center at Duke University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimated): December 8, 2016

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Glioma; GBM; Brain tumor; Glioblastoma; Recurrent; PVSRIPO; Duke; Istari; rGBM; Pro00077024
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: Pro00077024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No