TY - JOUR
T1 - Evolution of the Innovative Therapies for Children With Cancer Consortium Trial Portfolio for Drug Development for Children With Cancer
AU - Innovative Therapies for Children with Cancer (ITCC) Consortium
AU - Bautista, Francisco
AU - Verdú-Amorós, Jaime
AU - Geoerger, Birgit
AU - Rubio-San-Simón, Alba
AU - Paoletti, Xavier
AU - Zwaan, C Michel
AU - Casanova, Michela
AU - Marshall, Lynley V
AU - Carceller, Fernando
AU - Doz, Francois
AU - Lecinse, Carole
AU - Vassal, Gilles
AU - Pearson, Andrew D J
AU - Kearns, Pamela
AU - Moreno, Lucas
PY - 2024/5/14
Y1 - 2024/5/14
N2 - PURPOSE: The aim of the Innovative Therapies for Children with Cancer (ITCC) consortium is to improve access to novel therapies for children and adolescents with cancer. The evolution of the ITCC clinical trial portfolio since 2003 was reviewed.METHODS: All ITCC-labeled phase I/II trials opened between January 1, 2003 and February 3, 2018 were analyzed in two periods (2003-2010 and 2011-2018), and data were extracted from the ITCC database, regulatory agencies' registries, and publications.RESULTS: Sixty-one trials (62% industry-sponsored) enrolled 3,198 patients. The number of trials in the second period increased by almost 300% (16
v 45). All biomarker-driven trials (n = 14) were conducted in the second period. The use of rolling six and model-based designs increased (1 of 9, 11%
v 21 of 31, 68%), and that of 3 + 3 designs decreased (5 of 9, 55%
v 5 of 31, 16%;
P = .014). The proportion of studies evaluating chemotherapeutics only decreased (5 of 16, 31%
v 4 of 45, 9%), the proportion of single-agent targeted therapies did not change (9 of 16, 56.2%
v 24 of 45, 53.3%), the proportion of combination targeted therapies trials increased (2 of 16, 12%,
v 17 of 45, 38%), the proportion of randomized phase II trials increased (1 of 7, 14%
v 8 of 14, 57%). More trials were part of a pediatric investigation plan in the second period (4 of 16, 25%
v 21 of 45, 46%). The median time for Ethics Committees' approvals was 1.7 times longer for academic compared with industry-sponsored trials.
CONCLUSION: This study reports a shift in the paradigm of early drug development for childhood cancers, with more biologically relevant targets evaluated in biomarker-driven trials or in combination with other therapies and with more model-based or randomized designs and a greater focus on fulfilling regulatory requirements. Improvement of trial setup and recruitment could increase the number of patients benefiting from novel agents.
AB - PURPOSE: The aim of the Innovative Therapies for Children with Cancer (ITCC) consortium is to improve access to novel therapies for children and adolescents with cancer. The evolution of the ITCC clinical trial portfolio since 2003 was reviewed.METHODS: All ITCC-labeled phase I/II trials opened between January 1, 2003 and February 3, 2018 were analyzed in two periods (2003-2010 and 2011-2018), and data were extracted from the ITCC database, regulatory agencies' registries, and publications.RESULTS: Sixty-one trials (62% industry-sponsored) enrolled 3,198 patients. The number of trials in the second period increased by almost 300% (16
v 45). All biomarker-driven trials (n = 14) were conducted in the second period. The use of rolling six and model-based designs increased (1 of 9, 11%
v 21 of 31, 68%), and that of 3 + 3 designs decreased (5 of 9, 55%
v 5 of 31, 16%;
P = .014). The proportion of studies evaluating chemotherapeutics only decreased (5 of 16, 31%
v 4 of 45, 9%), the proportion of single-agent targeted therapies did not change (9 of 16, 56.2%
v 24 of 45, 53.3%), the proportion of combination targeted therapies trials increased (2 of 16, 12%,
v 17 of 45, 38%), the proportion of randomized phase II trials increased (1 of 7, 14%
v 8 of 14, 57%). More trials were part of a pediatric investigation plan in the second period (4 of 16, 25%
v 21 of 45, 46%). The median time for Ethics Committees' approvals was 1.7 times longer for academic compared with industry-sponsored trials.
CONCLUSION: This study reports a shift in the paradigm of early drug development for childhood cancers, with more biologically relevant targets evaluated in biomarker-driven trials or in combination with other therapies and with more model-based or randomized designs and a greater focus on fulfilling regulatory requirements. Improvement of trial setup and recruitment could increase the number of patients benefiting from novel agents.
U2 - 10.1200/JCO.23.01237
DO - 10.1200/JCO.23.01237
M3 - Article
C2 - 38743911
SN - 0732-183X
SP - JCO2301237
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
ER -
