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.
Subjects with radiologic evidence of intracranial recurrence or progression of a previously diagnosed high-grade astrocytoma.
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.
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 leukocytosis
Serum antibodies to human immunodeficiency virus (HIV)
Previous history of liver disease including autoimmune or viral hepatitis
Positive serologic test for Hepatitis B or C at baseline
Sequential
Ad5-yCD/mutTKSR39rep-ADP adenovirus and fractionated stereotactic radiosurgery (fSRS)
Biological/VaccineAd5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral
Maximum Tolerated Dose
The primary objective is to determine the maximum tolerated dose of injected of Ad5-yCD/mutTKSR39rep-ADP adenovirus into the resection cavity at the time of surgery.
1. Assessment of antitumor immune response
Assessment of antitumor immune response by serum levels of interferon-gamma (IFN-γ) measured by ELISA and will be described by pico-gram per milliliter (pg/mL).
2. Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts
Assessment of change in antitumor immune response by peripheral blood monoclonal cell (PBMC) counts measured by flow cytometry
Assessment of antitumor immune response by using antibodies against surface markers
Assessment of antitumor immune response by using antibodies against surface markers (CD3, CD56, CD4, CD8, CD45, CD69).
Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30
Assessment of quality of life (QOL) by using the European Organization for Research and Treatment of Cancer (EORTC) tools consisting of the EORTC QLQ-C30
Quality of life as assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20
Assessment of quality of life (QOL) by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BN20
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