Predictors of Success of Phase II Pediatric Oncology Clinical Trials.

Background: There are limited data to predict which novel childhood cancer therapies are likely to be successful. To help rectify this, we sought to identify the factors that impact the success of phase II clinical trials for pediatric malignancies.

Materials And Methods: We examined the impact of 24 preclinical and trial design variables for their influence on 132 phase II pediatric oncology clinical trials. Success was determined by an objective assessment of patient response, with data analyzed using Fisher's exact test, Pearson's chi-square test, and logistic regression models.

Results: Trials that evaluated patients with a single histological cancer type were more successful than those that assessed multiple different cancer types (68% vs. 47%, 27%, and 17% for 1, 2-3, 4-7, and 8+;  < .005). Trials on liquid or extracranial solid tumors were more successful than central nervous system or combined trials (70%, 60%, 38%, and 24%;  < .005), and trials of combination therapies were more successful than single agents (71% vs. 28%;  < .005). Trials that added therapies to standard treatment backbones were more successful than trials testing novel therapies alone or those that incorporated novel agents ( < .005), and trials initiated based on the results of adult studies were less likely to succeed ( < .05). For 61% of trials (80/132), we were unable to locate any relevant preclinical findings to support the trial. When preclinical studies were carried out (52/132), there was no evidence that the conduct of any preclinical experiments made the trial more likely to succeed ( < .005).

Conclusion: Phase II pediatric oncology clinical trials that examine a single cancer type and use combination therapies have the highest possibility of clinical success. Trials building upon a standard treatment regimen were also more successful. The conduct of preclinical experiments did not improve clinical success, emphasizing the need for a better understanding of the translational relevance of current preclinical testing paradigms.

Implications For Practice: To improve the clinical outcomes of phase II childhood cancer trials, this study identified factors impacting clinical success. These results have the potential to impact not only the design of future clinical trials but also the assessment of preclinical studies moving forward. This work found that trials on one histological cancer type and trials testing combination therapies had the highest possibility of success. Incorporation of novel therapies into standard treatment backbones led to higher success rates than testing novel therapies alone. This study found that most trials had no preclinical evidence to support initiation, and even when preclinical studies were available, they did not result in improved success.