Topics to address in the Background and Rationale Section include:
- Background Information: sufficient information to identify and clarify the scientific and medical context from which the opportunity emerges.
- Preclinical molecular target (mechanism of action): Sufficient information should be provided to document the degree of specificity of the agent for its claimed molecular target(s) or mechanism of action. The known or potential relevance of the agent’s target or mechanism of action to childhood cancers should be summarized.)
- Preclinical in Vitro Studies: A summary of data from single agent in vitro studies and combination in vitro studies should be provided if performed.
- Preclinical in Vivo Studies: Summary of data concerning the in vivo anticancer activity of the agent should be summarized. In general, appropriate agent administration schedules for demonstrating anti-cancer activity and the maximum tolerated doses for these schedules should be known at the time that an agent is proposed for pediatric preclinical testing. For most agents, these data will likely be primarily taken from adult cancer preclinical models, but data from pediatric models should be provided as well when available.
- Preclinical Pharmacokinetics (when available): Of particular interest is the availability of pharmacokinetic data from preclinical models used to demonstrate efficacy.
- Status of Clinical Development: Priority is given to studying agents that are entering (or have entered) clinical evaluation. Information concerning the current status of the clinical development of the agent should be provided, along with any plans for potential pediatric evaluations of the agent.