The proposal outlines a plan for the evaluation of Phase I agents in children using the Pediatric Oncology Group (POG) consortium.
The aims are to: (1) establish the maximum tolerated dose and dose-limiting toxicities of new cytotoxic agents, biological response modifiers, or maturational agents; (2) determine the quantitative and qualitative toxicity of new agents, the supportive care necessary and the precautions to be observed; (3) establish doses and schedules which can be used in Phase II trials; (4) note any antitumor effects of the tested agents at all dose levels, or evidence of biologic modulation or maturation, and correlate response with the pharmacokinetic, biological modulation and/or maturational data; (5) conduct pharmacodynamic and/or pharmacokinetic studies of new cytotoxic agents, and appropriate pharmacokinetic and correlative biological studies on biologic response modifier agents and maturational agents, and compare the results obtained with those obtained in animals and/or adults; (6) characterize the range and distribution of pharmacokinetic parameters and determine whether these parameters correlate with clinical variables such as plasma protein concentrations, creatinine clearance, etc.; (7) establish and validate an electronic data transmission system for pediatric Phase I trials; (8) closely monitor activities of investigators and reference laboratories; (9) provide CTEP and the NCI with timely reports of studies; and (10) increase the use of preclinical screening of cytotoxic and biologic agents in the selection of medications for entry into Phase I trials in children. In order to improve patient accrual, the current institutional pool will be expanded to all full-member institutions which also demonstrate an interest in Phase I trials, two available Phase I investigators, an ability to procure the necessary pharmacokinetic samples, an ability to enroll at least three patients per year, adequate facilities, adequate drug storage and logs, and an ability to transmit data electronically by July 1, 1997. New agents may be proposed by any investigator. The proposal will then be reviewed by a decision group, which includes the pharmacology chair, the new agents and pharmacology chair and the biologic response modifier chair. If the project is approved, the study coordinator and the operations office are involved, and a letter of intent (LOI) is submitted to CTEP. If the LOI is approved, a protocol will be prepared by the study coordinator. The protocol will be reviewed by the New Agents and Pharmacology (NAP) Core Committee and the Operations Office. After appropriate revision, the protocol is submitted to CTEP. After approval by CTEP, the protocol will circulate to the statistical office two weeks prior to activation for patient registration setup and fast fact sheet preparation, and is then distributed via the newsletter. The NAP chair/scientific Principal Investigator will have the overall scientific responsibility for the successful and timely completion of Phase I trials.
