CNS 18 - 17 
9.0 OFF STUDY CRITERIA 
9.1 Progressive disease at any time after treatment. 
9.2 Refusal of further therapy by the patient or legal guardian. 
9.3 Development of unacceptable toxicity or death on study. Notify Principal 
investigator immediately. 
10.0 STATISTICAL CONSIDERATIONS 
This is a feasibility/phase I (no dose escalation) clinical trial which has the primary 
objective of evaluating the toxicity associated with intratumoral transduction with the 
thymidine kinase gene and subsequent treatment with intravenous ganciclovir. The 
statistical design is adapted from the CTEP recommended design for phase I trials in 
pediatric oncology and requires the successfully study of at most six patients. Patients 
will be treated one at a time and the trial will be terminated when two toxic episodes 
have been observed or six patients have been treated with one or none having 
experienced unacceptable toxicity. The above design has 34%, 58%, and 89% chance 
of identifying the regimen as having unacceptable toxicity if the true toxic rate is 20%, 
30% or 50, respectively. 
If one or none the six evaluable patients experience unacceptable toxicity, the regimen 
will be considered feasible and permission for a disease specific phase II trial will be 
sought to investigate efficacy. 
A total of 31 previously untreated patients who would ultimately have been eligible for 
this protocol were seen at SJCRH from January, 1989 to June, 1993. Based on this, 7 
patients/year are expected to be eligible for this study. Furthermore, it is anticipated that 
the numbers of eligible patients may be substantially increased, if required, through 
accession of previously treated patients with recurrent tumors. 
11.0 DATA MANAGEMENT/REPORTING REQUIREMENTS 
f 
Data including prior and current therapies, clinical status, laboratory results, neurologic 
and imaging evaluations, will be compiled and maintained by the data manager (L. 
Ogle), This information will be mailed to NCI investigators every 1-2 months as well 
as other monitoring agencies, when appropriate. 
Adverse drug reactions are to be promptly reported to the Investigational Drug Branch, 
NCI, phone (301) 496-7957. These reports are required even if the event is only a 
suspicious for a drug effect. Previously unknown grade 1,2, and 3 reactions will be 
reported in writing using the 'NCI forms within 10 working days ( Send to: 
Investigational Drug Branch, Cancer Therapy Evaluation Program, P.O. Box 30012, 
Bethesda, MD 20824). Grade 4 reactions, or deaths on study must be reported to the 
IRB within 24 hrs, with a written report to follow within 10 working days. 
[ 320 ] 
Recombinant DNA Research, Volume 18 
