PVSRIPO for Recurrent Glioblastoma (GBM)

Inclusion Criteria

• Disease Status. Patients must have a recurrent supratentorial WHO Grade IV malignant glioma based on imaging studies with measurable disease (≥ 1 cm or ≤ 5.5 cm of contrast-enhancing tumor). Prior histopathology consistent with a World Health Organization (WHO) Grade IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designate.
• Age. Due to the potential implications of the treatment on the developing CNS, all patients must be ≥ 18 years of age at the time of entry into the study.
• Performance Status. The patient must have a Karnofsky Performance Score (KPS) of ≥ 70% at the time of entry.
• Laboratory Studies
• Platelet count ≥ 125, 000/microliter prior to biopsy. Platelets ≥ 100,000/microliter prior to infusion
• Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy
• Positive serum anti-poliovirus titer prior to biopsy (except for retreatment)
• Creatinine ≤ 1.2 x normal prior to biopsy
• Total bilirubin, SGOT, SGPT, alkaline phosphatase ≤ 2.5 x normal prior to biopsy
• Neutrophil count ≥ 1000 prior to biopsy
• Hemoglobin ≥ 9 prior to biopsy
• Poliovirus Immunization Booster. The subject must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week prior to administration of the study agent.
• Disease Confirmation. At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
• Informed Consent. A signed informed consent form approved by the Duke University Institutional Review Board (IRB) will be required for patient enrollment into the study. Patients 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.
• Brain MRI. Able to undergo brain MRI with and without contrast

Exclusion Criteria

• Pregnancy. Because of the unknown risk of virus administration potentially affecting a developing fetus or growing infant, females who are pregnant or breast-feeding during the study period will be excluded. Adults of reproductive potential not employing an effective method of birth control will be excluded. Sexually active women of child bearing potential, whose partner is male, must use medically accepted birth control. Sexually active men, whose partner is a female of child bearing potential, must use a medically accepted birth control.
• Disease Status. Because patients will receive drug intracerebrally, patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, Allan Friedman, John Sampson, or Peter Fecci, or their designate, will be excluded.
• Medical Conditions. Because the potential toxicities from the agent being studied in this protocol may be similar to some known diseases or may be more dangerous in the context of certain known diseases, the following patients will be excluded to avoid confounding the study results:
• Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5 F/37.5 C).
• Patients with known immunosuppressive disease or known human immunodeficiency virus infection.
• Unstable or severe intercurrent medical conditions such as severe heart (New York Heart Association Class 3 or 4) or known lung (FEV1 < 50%) disease, uncontrolled diabetes mellitus.
• Albumin allergy. Albumin is added to the agent as a stabilizer. Patients with a known allergy will be excluded.
• Current or history of anaphylactic reaction to gadolinium. Gadolinium is used as contrast for the MRI.
• Previous Poliomyelitis. A history of neurological complications due to poliovirus 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.
• Prior Therapy.