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Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children | Clinical Trials | Clareo Health

COMPLETEDPHASE1

Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children

Phase Ib Study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

NCT03043391•Istari Oncology, Inc.

Summary

The purpose of the study is to confirm the safety of the selected dose and potential toxicity of oncolytic poliovirus (PV) immunotherapy with PVSRIPO for pediatric patients with recurrent WHO grade III or IV malignant glioma, but evidence for efficacy will also be sought. The primary objective is to confirm the safety of the selected dose of PVSRIPO when delivered intracerebrally by convection-enhanced delivery (CED) in children with recurrent WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma) or WHO Grade IV malignant glioma (glioblastoma, gliosarcoma). A secondary objective is to estimate overall survival (OS) in this population.

Detailed Description

PVSRIPO will be delivered intratumorally by CED using an intracerebral catheter placed within the enhancing portion of the tumor. The population group are patients with recurrent WHO grade III or IV malignant glioma who are aged 12 through 21 years old. After a single dose of PVSRIPO, subjects will return for periodic visits to monitor tumor status, adverse events, and changes in blood immune profiles. A maximum of 12 pediatric patients will be treated with PVSRIPO, and then carefully monitored for safety for at least a year after treatment.

Eligibility

Age

12 - 21 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients must have a recurrent supratentorial WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, ependymoma) or WHO Grade IV malignant glioma, medulloblastoma, or atypical teratoid/rhabdoid tumor (ATRT) based on imaging studies with measurable disease (≥ 1 cm and ≤ 5.5 cm). The prior histopathology must be consistent with a World Health Organization (WHO) Grade III or IV malignant tumor confirmed by the study pathologist, Roger McLendon, or his designee.
•There is no standard of care treatment for children with Grade III/IV gliomas; however, patients must have received some form of definitive treatment, i.e., standard therapy with known clinical benefit, for their initial diagnosis prior to their recurrence/progression. Definitive treatment includes maximal safe resection (if possible) and radiation therapy with or without chemotherapy. (Please note that patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e., Gorlin's syndrome or NF1 mutation) are still eligible to participate).
•Due to the potential implications of the treatment on the developing CNS, all patients must be ≥ 12 years of age and ≤ 21 years of age at the time of entry into the study.
•The patient must have a Lansky or Karnofsky Performance Score (KPS) of ≥ 70% at the time of entry.
•Laboratory Studies:
•1. Platelet count ≥ 125,000 per microliter prior to biopsy. Platelets ≥ 100,000 per microliter prior to infusion;
•2. Prothrombin and Activated Partial Thromboplastin Times ≤ 1.2 x upper limit of normal (ULN) prior to biopsy;
•3. Positive serum anti-poliovirus titer ≥ 1:8 prior to biopsy;
•4. Creatinine ≤ 1.2 x ULN prior to biopsy;
•5. Total bilirubin, AST, ALT, alkaline phosphatase ≤ 2.5 x ULN prior to biopsy;
+6 more criteria

Exclusion Criteria

•Pregnant or breast-feeding. Female patients of child-bearing potential or female sexual partners (who are of child-bearing potential) of male patients must use at least one of the following methods of medically acceptable contraceptives: approved hormonal contraceptives (such as birth control pills, patches, implants or infusions), an intrauterine device (IUD), or a barrier method of contraception (such as a condom or diaphragm) used ith spermicide. Because all patients are required to have a boost immunization of trivalent inactivated IPOL™, there should be no risk of transmission of a mother to her fetus after receiving intracranial PVSRIPO. As such, patients who become pregnant after receiving PVSRIPO will continue to be monitored in the same manner, i.e. per protocol, unless the assessment is contra-indicated during pregnancy. Partners who become pregnant will sign a Pregnant Partner Information Form and information regarding the pregnancy and its outcome may be collected.
•Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeon.
•Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F).
•Patients with known immunosuppressive disease or known human immunodeficiency virus infection.
•Patients with unstable or severe intercurrent medical conditions such as severe heart (New York Heart Association Class 3 or 4) or lung (FEV1 \< 50%) disease, uncontrolled diabetes mellitus.
•Patients with allergy to human serum albumin.
•Current or history of anaphylactic reaction to gadolinium.
•A history of neurological complications due to past PV infection would imply previous virus replication in the CNS. Based on animal studies, previous exposure to poliovirus administered intracerebrally can reduce subsequent virus replication in the CNS.
•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:
•1. Patients who are less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 consecutive scans with disease progression or histopathologic confirmation of recurrent tumor.
+8 more criteria

Locations (1)

Duke University Medical Center

Durham, North Carolina, United States

Key Dates

Start Date

November 7, 2017

Primary Completion Date

March 23, 2022

Completion Date

March 23, 2022

Last Updated

April 8, 2024

Enrollment

ACTUAL participants

Conditions

Malignant GliomaAnaplastic AstrocytomaAnaplastic OligoastrocytomaAnaplastic OligodendrogliomaGlioblastomaGliosarcomaAtypical Teratoid/Rhabdoid Tumor of BrainMedulloblastomaEpendymomaPleomorphic Xanthoastrocytoma of BrainEmbryonal Tumor of Brain

Interventions

Polio/Rhinovirus Recombinant (PVSRIPO)

BIOLOGICAL

A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)

NCT05099003

Malignant Glioma

View study

RECRUITING

Targeted Pediatric High-Grade Glioma Therapy

NCT05839379

High Grade GliomaDiffuse Intrinsic Pontine Glioma+7 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: April 8, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children

Inclusion Criteria

Exclusion Criteria

A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)

Targeted Pediatric High-Grade Glioma Therapy

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