(Journal of Molecular Oncology Research) Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies


Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) <10%. Recently, with an emphasis on targeted approaches, response rates may have changed. Authors analyzed outcomes of recent phase I pediatric oncology trials.

This was a systematic review of phase I pediatric oncology trials published in 2012–2017, identified through PubMed and EMBASE searches conducted on March 14, 2018. Selection criteria included full‐text articles with a pediatric population, cancer diagnosis, and a dose escalation schema. Each publication was evaluated for patient characteristics, therapy type, trial design, toxicity, and response.

Of 3,431 citations, 109 studies (2,713 patients) met eligibility criteria. Of these, 78 (72%) trials incorporated targeted therapies. Median age at enrollment/trial was 11 years (range 3–21 years). There were 2,471 patients (91%) evaluable for toxicity, of whom 300 (12.1%) experienced dose‐limiting toxicity (DLT). Of 2,143 patients evaluable for response, 327 (15.3%) demonstrated an objective response. Forty‐three (39%) trials had no objective responses. Nineteen trials (17%) had an ORR >25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58).

Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target‐specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials.

Implications for Practice

Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.

Best Regards,


Managing Editor

Journal of Molecular Oncology Research


Email: oncology@openaccessjournal.org