A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors

This is an Open label, Phase I, dose escalation study. Patients will receive an injection of
AdV-tk into the tumor or tumor bed during the surgical procedure followed by 14 days of
anti-herpetic prodrug, valacyclovir, starting 1-3 days after vector injection. Standard
radiotherapy will begin 3-7 days after AdV-tK injection. Standard chemotherapy may begin
after completion of valacyclovir at the discretion of the treating physician and family. Two
dose levels of AdV-tk will be evaluated with a fixed dose of valacyclovir.

Inclusion Criteria:

- Patients must be 3 years of age or older

- Patients must be planning to undergo standard of care treatment with surgery and
radiation therapy.

- Patients must have malignant glioma or recurrent ependymoma

- Tumor must be accessible for injection and must not be located in the brainstem or
deep midbrain

- Performance Score: Karnofsky ≥60% if >10y/o, Lansky ≥60 if ≤10y/o

- Bone Marrow Function: Patients must have adequate bone marrow function defined as a
peripheral absolute neutrophil count ≥ 1000/µl, platelet count ≥ 100,000/µl
(transfusion independent) and hemoglobin ≥ 8.0 gm/dL

- Renal Function: Patients must have serum creatinine ≤ 1.5 times upper limit of
institutional normal for age and/or GFR ≥ 70 mL/min/1.73 m2.

- Hepatic Function: Bilirubin ≤ 1.5 times institutional normal; SGPT (ALT) < 3 times
institutional normal

- Serum electrolyte values (sodium, potassium, magnesium, calcium) must be checked prior
to enrollment and clinically significant abnormalities corrected prior to
surgery/AdV-tk injection

- Patients with seizure disorder may be enrolled if well controlled

- Signed informed consent according to institutional guidelines must be obtained

Exclusion Criteria:

- Prior or ongoing liver disease including known cirrhosis, hepatitis B or C infection
but not to exclude patients with a distant history of resolved hepatitis A infection

- Patients on immunosuppressive drugs (with exception of corticosteroid)

- Known history of HIV or underlying immunodeficiency

- Patients with acute infections (viral, bacterial or fungal infections requiring
therapy)

- Pregnant or breast-feeding patients. Female patients of childbearing age must have
negative serum or urine pregnancy test within 1 week of beginning therapy

- Other serious co-morbid illness or compromised organ function

- No other investigational anti-tumor agents within 30 days prior to study entry or
during active participation in the study (defined as from study entry until tumor
progression)