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.
Detailed study description: Patients with recurrent glioblastoma (GBM) or progressive high grade astrocytoma who are scheduled to undergo repeat surgery are eligible. After the removal of as much tumor tissue as possible, a modified oncolytic adenovirus is injected into the wall of the resection cavity and any residual tumor tissue. The goal of this study is to determine the maximum tolerated dose (MTD) of the injected adenovirus. This treatment is combined with a combination of oral 5-fluorocytosine (5-FC) and valganciclovir (vGCV) prodrug therapy. Following the surgery, patients will be treated with fractionated radiosurgery (fSRS). Patients will be monitored for 30 days before they start on next line anti-cancer therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Ad5-yCD/mutTKSR39rep-ADP adenovirus will be injected intratumoral
Henry Ford Health System
Detroit, Michigan, United States
RECRUITINGMaximum 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.
Time frame: 30 days
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).
Time frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.
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
Time frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.
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).
Time frame: Pre-surgery (day 0), 3, 7, 14, 21, 30, 90 days.
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