Approaches to Child-First Trials in Pediatric Oncology

Statement of Need

First-in-child clinical trials of anti-cancer drugs almost always follow initial testing in adult cancer populations, providing critical safety, pharmacokinetic, and dosing data to inform the pediatric trial. Advances in precision pediatric oncology and immunotherapy, such as innovative and pediatric specific cell therapies, may require development of new agents only relevant to pediatric and not adult cancer populations. To ensure timely evaluation of novel agents for children with life-threatening malignancies, we must anticipate a need for “child-first” trials that advance to the clinic without data from early phase adult cancer trials. Such development raises unique ethical, regulatory, scientific, and patient-centered challenges. This invitation only workshop aims to address these challenges by developing a shared framework for responsible, efficient, and globally-coordinated child-first drug development.

Issues related to child-first trials also impact the development of innovative therapies for rare or ultra rare pediatric diseases, such as patient specific in vivo gene editing to treat an inborn error of metabolism. The workshop will be inspired by lessons learnt in this field and develop recommendations.

From the patient and family perspective, delays in accessing targeted therapies and personalized immunotherapies, lack of alternatives, and reliance on adult-centric models all contribute to treatment inequities and missed therapeutic opportunities. A child-first approach must therefore be crafted with rigorous safeguards, transparent communication, and meaningful participation of patients and families.

Objectives:



1. Frame ethical principles relevant to conducting child-first cancer clinical trials.
2. Understand how child-first trials have been conducted in other rare pediatric life-threatening conditions
3. Understand scope of child-first trials in pediatric oncology
4. Develop a multistakeholder framework for the design and conduct of child-first trials in oncology
5. Identify and propose potential solutions to facilitate the conduct of child-first trials.