surgery, the tumor bed will be infiltrated with the same dose of H5.010RSV77C as used in the patient's 
first treatment. GCV will be given for 14 days following tumor resection. 
III.C Evaluation for Safety 
III.C.1 Neurologic and surgical risk. 
Patients may be at risk for the usual complications of brain surgery which include hemorrhage, edema, 
permanent or temporary neurological damage or infection. Preoperative corticosteroids will be given 
to decrease these risks. Careful neurolgic examination will be performed daily while patients are 
hospitalized (for two weeks after the surgical injection of the virus), and a record will be kept of the 
neurolgic findings. The physician will assess for level of consciousness, signs of increased intracranial 
pressure, seizure activity and focal signs. The MRI scan will be repeated once weekly for two weeks, 
and then monthly. In case of any unexpected neureolgic changes which persist, the MRI will be 
performed more frequently. The MRI will be used to assess for increased edema and postoperative 
hemorrhage. Increased intracranial pressure will be treated with higher doses of corticosteroid or 
Mannitol. Prophylactic antibiotics will be given to reduce the risk of wound infection, which may be 
greater than average because of the previous surgery and scalp irradiation these patients have received. 
III.C. 2 Virus Infection. 
Patients will be assessed for evidence of virus dissemination, with chest x-rays, examination of spinal 
fluid in patients where it is deemed safe to perform a lumbar puncture, and MRI will be analyzed for 
signs of encephalitis and meningitis. Biopsies performed after viral injection in patients with 
resectable tumor will be submitted for viral culture and histologic examination for encephalitis. 
III.C. 3 Ganciclovir Toxicity 
The major toxicity is expected to be myelo suppression. Complete blood counts will be performed every 
2 to 3 days after adenovirus treatment. Dose adjustment for myelo toxicity will be as follows: absolute 
granulocyte count (polymorphs and bands) < 1000/mm 3 or platelet count < 100,000/mm 3 : reduce 
dose to 75% ; absolute granulocyte count < 500/mm 3 or platelet count < 50,000/mm 3 : discontinue 
ganciclovir, and resume the drug at 50% of the original dose when the granulocyte count is > 500 and 
platelets > 50,000. Less frequent side effects of ganciclovir include headache, venous irritation with 
pain or redness, renal insufficiency, infertility, birth defects, fever, rash, and liver function 
abnormalities. Patients will be assessed for headache and fever and treated symptomatically but the dose 
will not be adjusted. Venous irritation will be avoided by the use of central venous catheters (such as a 
Hickman port or Portacath) in patents who have poor venous access. Renal function tests (BUN, 
Creatinine) will be performed weekly. If the level of creatinine rises to > 2, the ganciclovir will be 
discontinued until the creatinine falls below 2 and then resumed at 75% of the original dose. Women of 
child bearing age will be requested to use effective contraceptives during and for 3 months after the 
treatment. Ganciclovir will be discontinued if grade 3 or 4 skin or hepatic toxicity occurs (see 
Appendix VI. H, page 44, for toxicity criteria). 
III.C. 4 Dose escalation 
Patients will be enrolled in phase IA and phase IB studies in groups of three. Each group will be followed 
for a minimum of 30 days before enrolling patients to the next higher dose within each study. If one or 
more patients in a group develop dose limiting toxicity, then three subsequent patients will be enrolled 
at a one log lower dose. If these patients are successfully treated without dose limiting toxicity, then 
treatment at the next higher dose will be done in three additional patients. If none of these patients 
experience dose limiting toxicity, the planned dose escalations will continue. If any develop dose limiting 
toxicity, the study will stop enrolling patients. 
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