Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children

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:
• Platelet count ≥ 125, 000 per microliter prior to biopsy. Platelets ≥ 100,000 per microliter prior to infusion;
• Prothrombin and Activated Partial Thromboplastin Times ≤ 1.2 x upper limit of normal (ULN) prior to biopsy;
• Positive serum anti-poliovirus titer ≥ 1: 8 prior to biopsy;
• Creatinine ≤ 1.2 x ULN prior to biopsy;
• Total bilirubin, AST, ALT, alkaline phosphatase ≤ 2.5 x ULN prior to biopsy;
• Neutrophil count ≥ 1000 per microliter prior to biopsy;
• Hemoglobin ≥ 9 gm/dl prior to biopsy (can be transfused).
• The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) ≥ 1 week prior to administration of the study agent.
• At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
• A signed informed consent form approved by the Duke University Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients (if 18 years old) or their parent(s) or guardian(s) must be able to read and understand the informed consent document and must sign the informed consent indicating that they are aware of the investigational nature of this study. All children will have to provide assent to the study.
• Able to undergo brain MRI with and without contrast without requiring general anesthesia.

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 t