Safety and outcome of children, adolescents and young adults participating in phase I/II clinical oncology trials: a 9-year center experience.

Introduction: Enrolling children with cancer in early phase trials is crucial to access innovative treatments, contributing to advancing pediatric oncology research and providing tailored therapeutic options. Our objective is to analyze the impact of these trials on patient outcomes and safety, and to examine the evolution and feasibility of trials in pediatric cancer over the past decade.
Methods: All patients recruited in pediatric anticancer phase I/II clinical trials from January 2014 to December 2022 were included. Clinical records and trial protocols were analyzed.
Results: A total of 215 patients (median age 11.2 years, range 1-29.5) were included in 52 trials (258 inclusions). Patients with extracranial solid tumors (67%), central nervous system (CNS) tumors (24%), and leukemia (9%) were included. The most common investigational drugs were small molecules (28.3%) and antibodies (20.5%). Serious adverse events were experienced by 41% of patients, 4.4% discontinued treatment because of toxicity and two had toxic deaths. Median event-free survival was 3.7 months (95%CI: 2.8-4.5), longer in phase II trials than in phase I (2 vs. 6.3 months; p  ≤ 0.001). Median overall survival was 12 months (95%CI: 9-15), higher in target-specific vs. non-target-specific trials (14 vs. 6 months; p  ≤ 0.001).
Discussion: A significant and increasing number of patients have been included in early clinical trials, suggesting that both oncologists and families consider it valuable to be referred to specialized Units to access new therapies. Moreover, our data suggests that participation in early clinical trials, although not without potential toxicities, might have a positive impact on individual outcomes.
Competing Interests: AR-S-S had a consulting role for EusaPharma, Sanofi and SERB. She received honoraria from EusaPharma and Roche. FB has been a member of a data monitoring committee (DMC) in a clinical trial sponsored by Sanofi, had a consulting or advisory role for Bayer, Amgen, Roche Genentech, EusaPharma and Eisai and received honoraria from Servier (through his current affiliation). LM is member of a Data Monitoring Committee (DMC) for clinical trials sponsored by Novartis, Actuate Therapeutics, Shionogi, Incyte, the University of Southampton and the Royal Marsden NHS Foundation Trust; had a consulting role for Novartis, Bayer, BMS, Merck, Gilead and Shionogi, has received travel expenses from Recordati Rare Diseases and is member of the Executive Committee of SIOPEN (European neuroblastoma research cooperative group), organization which receives royalties for the sales of dinutuximab beta. His institution receives funding from sponsors for DMC participation, advisory role or conducting industry-sponsored clinical trials. LS received honoraria as consultant from Sobi, Agios, Novartis, Amgen and Rocket Pharmaceuticals Inc. He has also licensed medicinal products from Rocket Pharmaceuticals Inc. JV-A received honoraria from EusaPharma, Jazz Pharmaceuticals and Servier. M Ramirez has received honoraria for participation in advisory boards from Amplicell and stock options from Orgenesis. AL received honoraria from Servier, Alexion, and Lilly. BH received honoraria from Servier, Novartis and Pfizer. MA received honoraria from Servier and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2024 Pujol Manresa, Buendía López, Andión, Herrero, Lassaletta, Ramirez, Ruano, Hernández-Marqués, Varo, de Rojas, Cortés Hernández, Verdú-Amorós, Martín Prado, Artigas, Redondo, Ruiz Pato, Herreros López, Sevilla, Madero, Moreno, Bautista Sirvent and Rubio-San-Simón.)