Safety and Efficacy Study of REOLYSIN® in the Treatment of Recurrent Malignant Gliomas

Abbreviated Inclusion Criteria:

• PHASE I: 1st, 2nd or 3rd recurrence of: glioblastoma multiforme; gliosarcoma; anaplastic astrocytoma; anaplastic mixed glioma; or anaplastic oligodendroglioma
• PHASE II: 1st recurrence of glioblastoma multiforme (only)
• Progressing/recurrent lesion which is ≥1cmx1cm. For the Phase II study the lesion must be ≤5cmx5cm, defined by MRI only
• Be fully recovered from any prior therapy
• Have been treated at the time of original diagnosis by surgery and external beam radiation to a dose of at least 5000 cGy; radiotherapy completed at least 6 weeks before REOLYSIN® therapy
• Any intracranial surgery, except for stereotactic needle biopsy, must have occurred at least 4 weeks before REOLYSIN® therapy
• Any anti-cancer drug therapy must have been completed at least 4 weeks (6 weeks in the case of prior nitrosourea therapy) before REOLYSIN® therapy
• Have a life expectancy of ≥8 weeks and a Karnofsky Performance Status (KPS) of ≥60
• Absolute neutrophils ≥1.5 x10^9/L; hemoglobin ≥100g/L; platelets ≥100 x 10^9/L
• ALT ≥1.5 x ULN; total bilirubin ≥1.5 x ULN
• Serum creatinine ≤1.5 x ULN
• EKG with no evidence of active, acute cardiovascular disease
• PT within normal limit
• Women of childbearing potential must have a negative pregnancy test
• Reside or have suitable living arrangements within a reasonable geographical area of the study site and be able to participate in all follow-up visits
• Patients requiring corticosteroids must be on a stable dose of steroid for at least two weeks prior to baseline MRI and when entered in the study. Maximum daily dose of 24 mg/day of dexamethasone/decadron or equivalent

Abbreviated Exclusion Criteria:

• Patients who are sexually active and not willing to use barrier methods of contraception; women who are breastfeeding
• Patients with unstable or serious concurrent medical or psychiatric conditions that would interfere with study treatment or follow-up
• Patients with more than one discrete enhancing lesion on MRI, or radiographic evidence of satellite lesions or leptomeningeal disease not obviously contiguous by FLAIR imaging
• Patients who may require further neurosurgery within 4 weeks after REOLYSIN® treatment
• Patients with a prior history of encephalitis, multiple sclerosis or other significant chronic CNS disease
• Patients who have evidence of a current CNS infection, meningeal gliomatosis or gliomatosis cerebri
• Patients with tumor that to be treated would require needle or catheter passage through a ventricle, the posterior fossa or basal ganglia; or patients with tumors invading the ventricle
• Patients who have previously participated in experimental viral therapy protocols
• Patients who have had prior intratumoral gene therapy or other intratumoral therapies
• Patients who have had Gliadel wafer therapy less than 6 months prior to enrollment
• Patients who have a history of bleeding disorders including congenital or acquired coagulopathies
• Patients who have a known history of hepatitis or tuberculosis
• Patients who have a known history of hereditary or acquired immunodeficiency including HIV infection
• Patients who have impaired non-neurological organ function (>Grade 1)
• Patients who have used systemic antiviral (or potentially antiviral) therapies within 28 days of enrollment
• Patients who have had brachytherapy or radiosurgery to the brain at any time
• Patients with previous or concurrent malignancies at other sites (except surgically-cured carcinoma in situ of the cervix and non-melanoma skin cancer)
• Prior or current medical history indicating that a patient may be significantly immunosuppressed