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