specimens of those patients undergoing palliative resection following gene therapy, we will gain 
valuable information concerning the duration of transgene expression and extent of tumor penetration 
by adenovirus. 
III.B Study Design 
III.B.1 Patient Eligibilty 
III.B.I.a Patient Selection 
Eligible patients must be > 18 years old and have a histologic diagnosis of malignant glioma (anaplastic 
astrocytoma or glioblastoma), which has recurred after primary treatment. The first treatment must 
have included radiation therapy with or without chemotherapy. Radiation should have been completed at 
least 2 months prior to this study. There must be MRI scan evidence of tumor growth after treatment. 
Since treatment of glioma often induces brain edema or necrosis of brain, which may be difficult to 
distinguish from tumor growth, it is required that the tumor area show enhancement on MRI and that 
there be a clear increase in the enhancing area over a period of time. Positron emmission tomography 
(PET scan) will be used to help differentiate recurrent tumor from radiation necrosis. These techniques 
reflect metabolic activitiy in the brain, and generally demonstrate increased uptake of radionuclide in 
malignant tumor but decreased uptake in necrotic lesions. The aforementioned requirements should 
ensure that the patients selected for this study have recurrent disease despite standard therapy. Such 
patients have a median survival of 6 to 12 months, depending on their age and performance status. 
Therefore, this is an appropriate group for experimental therapy. 
The other eligibility requirements will help to select patients who can tolerate the proposed protocol 
with minimal concerns regarding safety. The patients must have no serious uncontrolled medical 
problems (such as infections, diabetes, angina, congestive heart failure). They must have a Karnofsky 
performance status of 70% or greater, meaning that they are independent in self care. Their MRI scan 
must show a tumor size of < 50cm 3 and no herniation or marked midline shift, so that they can 
undergo neurosurgery and injection of fluid into the brain. Solitary tumors are preferred. However, if 
the patient has multifocal glioma, the largest tumor must be in an area which can be surgically 
accessible for debulking. (Multifocal gliomas will offer an interesting opportunity to test the 
hypothesis that viral injection into one area of the brain will result in a "bystander effect "in distant 
regions.) The tumor for injection must not be adjacent to the optic chiasm or brain stem and must not 
be associated with subependymal spread. Patients will be recruited from all races and both genders will 
be equally represented. 
Laboratory evaluations prior to entry will include routine hematology, coagulation profile, chemistry 
test, chest x-ray, and EKG, all of which should be within normal limits. Mild abnormalities of liver 
function tests (less than 2 times the upper limit of normal) will be acceptable if patients are taking 
anticonvulsants which often cause these aberrations. A pregnancy test will be required in women of 
child bearing potential and such patients will be instructed to use contraception during and for 3 months 
after the adenovirus study. 
III.B.1 . b Screening evaluation 
Eligibility will be established by a review of the patients medical records with attention to the dose of 
radiation received, and a review of their MRI scans for tumor size and location. Two to three weeks 
prior to the planned therapy written informed consent will be obtained from the patient. Screening will 
consist of complete physical and neurological examinations, evaluation of performance status, blood 
chemistry screen, complete blood counts, blood coagulation profile, anti-adenovirus antibodies testing, 
pregnancy test (when indicated), chest x-ray, and review of prior histologic specimens from the brain 
tumor. 
III.B. 2 Imaging Studies 
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