Adenovirus Mediated Suicide Gene Therapy With Radiotherapy in Progressive Astrocytoma.

The primary goal of this Phase I study is to determine the maximum tolerated dose of oncolytic adenovirus mediated double suicide-gene therapy in combination with fractionated stereotactic radiosurgery in patients with recurrent high-grade astrocytoma undergoing resection.

Inclusion Criteria:Subjects with radiologic evidence of intracranial recurrence or progression of a previously diagnosed high-grade astrocytoma.To be eligible for this trial, the subjects must have:Histologically documented glioblastomas or anaplastic astrocytoma prior to the debulking surgery that is suspicious to have progressed on imaging. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiation while at least 4 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen.Patients must be ≥ 18 years of age, able to provide informed consent and express a willingness to meet all the expected requirements of the protocol for the duration of the study.Must have recovered from toxicity (grade 2 or less) of prior therapy.Eligible for partial or total resection of the recurrent tumorNo anticipated physical connection between post-resection tumor cavity and cerebral ventricleKarnofsky performance status (KPS) ≥ 60 at time of surgeryNo prior treatment of the tumor with gene or virus therapy, immunotherapy, brachytherapy, or implants of polymers containing chemotherapeutic agents (e.g. Gliadel Wafer)No immunosuppressive or immune disorderBaseline organ function testing intactPatients who are candidates for surgical debulking (re-resection) following recurrence of diseases based on multidisciplinary evaluation by neurosurgeons, radiation oncologists, neuro-radiologists, and neuro-oncologists.Subjects must have adequate baseline organ function, as assessed by the following laboratory values, within 30 days before initiating the study therapy:Adequate renal function with creatinine clearance ≥ 50 mL/min/m2Platelet count ≥ 100,000/μLAbsolute neutrophil count ≥ 1,000/μLHemoglobin > 10.0 g/dLBilirubin < 1.5 mg/dL; SGOT and SGPT < 2.5 times upper limit of normal (ULN).Women of child-bearing potential will be required to practice birth control for the duration of the treatment and for at least 90 days after surgery with intratumor virus inoculation. Men must use barrier protection for the duration of treatment and for at least 90 days after surgery with intratumor virus inoculation treatment.Exclusion Criteria:Acute infection. Acute infection is defined by any viral, bacterial, or fungal infection that has required active treatment and caused oral temperature >38.5oC and/or clinically significant leukocytosisSerum antibodies to human immunodeficiency virus (HIV)Previous history of liver disease including autoimmune or viral hepatitisPositive serologic test for Hepatitis B or C at baselineImmunosuppressive therapy except for corticosteroid useSerious medical or psychiatric illness or concomitant medication, which, in the judgment of the investigator, might interfere with the subject's ability to respond to or tolerate the treatment or complete the trialImpaired immunity or susceptibility to serious viral infectionsPregnant or lactating femalesAllergy to any product used on the protocolPatient is not able to undergo a brain MRI.Patients who are not eligible for debulking surgery or resection of recurrent disease will be considered ineligible.