Assessment of enrollment characteristics for Children’s Oncology Group (COG) upfront therapeutic clinical trials 2004-2015

Abstract

Background Improvements in pediatric cancer survival are attributed to cooperative clinical trials. Underrepresentation of specific demographic groups has been described in adult and pediatric cancer trials and poses a threat to the generalizability of results. An evaluation of data provided by the Children's Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed. Methods US cancer cases were estimated using incidence data and US population estimates from the Surveillance, Epidemiology, and End Results Program and compared to observed COG cases. Percent enrollment and standardized ratios of enrollment were calculated across demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available trials and assess age eligibility. Results 19.9% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were more represented across diseases and races/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors. Conclusion COG trial enrollment rates are declining when compared to previously published data, potentially from challenges in pediatric drug development, difficulty designing feasible trials for highly curable diagnoses, and issues ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/ young adult (AYA) population and younger patients with solid and CNS tumors remains a

Association Between Participation in Clinical Trials and Overall Survival Among Children With Intermediate- or High-risk Neuroblastoma

“…In a multivariable analysis accounting for age, disease stage, and ploidy, enrollment in a clinical trial was not significantly associated with OS, suggesting that differences in these features were associated with the observed difference in OS. Thus, there appears to be physician bias toward off-trial treatment of patients with intermediate-risk disease with more unfavorable tumor biology.Contrasting studies identifying discrepancies in clinical trial enrollment according to demographic features, such as older age, and race/ethnicity,28,[33][34][35][36][37][38][39][40] we found no evidence of bias in recruitment across demographic groups. Of the 3986 patients enrolled in studies, 12.9% were Black and 11.3% were Hispanic, mirroring the prevalence of Black and Hispanic individuals in the US population and in the overall neuroblastoma population in North America.…”

Navigating the Regulatory Landscape to Develop Pediatric Oncology Drugs: Expert Opinion Recommendations

“…As outlined above, fewer pediatric patients are available for clinical trials, compared with adult oncology populations. However, compared with the small proportion (~8%) [70] of adult cancer patients enrolled in clinical trials, trial enrollment is more common among pediatric cancer patients, with enrollment rates between 19.9% and 27.5% reported in the US [71], Canada [72], and New Zealand [73]. However, disparities have been observed in the proportion of patients enrolled across different pediatric age groups; notably, the proportion of adolescents participating in clinical trials is often smaller than for younger children [71].…”

NCI support for pediatric radiation therapy: Past, present, and future

“…These trials are in the early stages of individualizing treatment selection 11 . New trials involving the adolescent and young adult cohort are also in their early phases of deployment and represent close coordination between the adult NCTN groups and COG 12,13 …”