Related Experiment Videos
Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective
Lucas Moreno1, Andrew D J Pearson2, Xavier Paoletti3
1Paediatric Phase I-II Clinical Trials Unit, Paediatric Haematology &Oncology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain.
Abstract:
In the past decade, the landscape of drug development in oncology has evolved dramatically; however, this paradigm shift remains to be adopted in early phase clinical trial designs for studies of molecularly targeted agents and immunotherapeutic agents in paediatric malignancies. In drug development, prioritization of drugs on the basis of knowledge of tumour biology, molecular 'drivers' of disease and a drug's mechanism of action, and therapeutic unmet needs are key elements; these aspects are relevant to early phase paediatric trials, in which molecular profiling is strongly encouraged. Herein, we describe the strategy of the Innovative Therapies for Children with Cancer (ITCC) Consortium, which advocates for the adoption of trial designs that enable uninterrupted patient recruitment, the extrapolation from studies in adults when possible, and the inclusion of expansion cohorts. If a drug has neither serious dose-related toxicities nor a narrow therapeutic index, then studies should generally be started at the adult recommended phase II dose corrected for body surface area, and act as dose-confirmation studies. The use of adaptive trial designs will enable drugs with promising activity to progress rapidly to randomized studies and, therefore, will substantially accelerate drug development for children and adolescents with cancer.
Insights
Innovative trial designs are crucial for accelerating the development of targeted and immunotherapy drugs for paediatric cancers. The Innovative Therapies for Children with Cancer (ITCC) Consortium proposes strategies to improve early phase clinical trials for children.
Area of Science:
- Oncology
- Paediatric Malignancies
- Clinical Trial Design
Background:
- Drug development in oncology has advanced, but early phase trials for paediatric cancers lag behind.
- Molecularly targeted agents and immunotherapies require adapted trial designs for children.
Purpose of the Study:
- To describe the Innovative Therapies for Children with Cancer (ITCC) Consortium's strategy for optimising early phase paediatric cancer trials.
- To advocate for trial designs that facilitate patient recruitment and accelerate drug development.
Main Methods:
- Adopting trial designs enabling uninterrupted patient recruitment.
- Extrapolating data from adult studies where feasible.
- Including expansion cohorts and utilizing adaptive designs.
- Starting dose-confirmation studies at the adult recommended phase II dose (adjusted for body surface area) for drugs without serious toxicities or narrow therapeutic index.
Main Results:
- Proposed strategies aim to streamline the drug development process for paediatric malignancies.
- Adaptive designs can accelerate promising drugs into randomized studies.
Conclusions:
- Implementing ITCC Consortium's strategies can significantly speed up the availability of novel cancer therapies for children and adolescents.
- Optimized trial designs are essential to address therapeutic unmet needs in paediatric oncology.