Voices of children and adolescents on phase 1 or phase 2 cancer trials: A new trial endpoint?

Abstract

Background Pediatric participants on Phase I or Phase II clinical trials for incurable cancer are at risk of experiencing toxicities (adverse events, AEs) related to trial participation. Multiple AEs are subjective; thus, the real impact of trial treatment cannot be known unless patient subjective reports are solicited. Methods We assessed the feasibility and acceptability of soliciting symptom, function and quality of life (QoL) reports from 8- to 18-year-old participants enrolled on Phase I/II clinical trials at four cancer centers during the first course of chemotherapy. We also assessed the reliability and validity of six self-report PROMIS pediatric measures and four open-ended interview questions at two time points (trial enrollment, T1 and 3 to 4 weeks later, T2). Results The enrollment rate of 75.9% (n=20) exceeded our feasibility criterion, and missingness of measures by person, measure and items at T1 and T2 were lower than our acceptability criteria. New QoL themes were limited to the impact of treatment on families and being away from home, family and friends for treatment. All but one measure at T1 met the reliability criterion and all did at T2. Validity support was limited though as theorized, mobility decreased and fatigue increased as AEs increased. Conclusions Soliciting and documenting symptom, function and QoL reports from 8- to 18-year-olds enrolled on a Phase I/II clinical trial is feasible and acceptable to participants, particularly when embedded in trials. Reliable and valid findings can result, making patient self-reported outcomes a possible new trial endpoint.

PROMIS pediatric measures validated in a longitudinal study design in pediatric oncology

“…To be embedded, pediatric self‐report measures must have demonstrated responsiveness to change. Responsiveness in pediatric PROs is rarely measured or achieved in pediatric cancer clinical trials . This study directly addressed responsiveness, construct, and concurrent validity of selected PROMIS pediatric short‐form psychological, symptom, and performance measures in order to assess their appropriateness for pediatric cancer clinical trials.…”

Comparison of Legacy Fatigue Measures With the PROMIS Pediatric Fatigue Short Form

“…Feasibility, acceptability, reliability, and knowngroup validity of the original eight PROMIS pediatric measures have been established in pediatric patients with cancer in cure-directed treatment, in survivorship, and in enrollment in phase 1 or 2 trials for incurable cancer (Dobrozsi et al, 2017;Hinds et al, 2013Hinds et al, , 2017. Evaluating the measures' responsiveness to capture change over time is essential to inform their use in clinical trials.…”

Utilization of palliative care consultations in pediatric oncology phase I clinical trials

“…Patients participating in early‐phase clinical trials have reported distressing symptoms, including anxiety and/or depression (70‐80%), pain (90%), and fatigue (85%) . To add to this complexity, patients and families often enroll in experimental therapy away from their primary institution, their home, and their support systems.…”

“…[9][10][11][12] Patients participating in early-phase clinical trials have reported distressing symptoms, including anxiety and/or depression (70-80%), pain (90%), and fatigue (85%). 13 To add to this complexity, patients and families often enroll in experimental therapy away from their primary institution, their home, and their support systems. Systematic integration of palliative care considerations into phase I clinical trials has the potential to improve patients' experience, as supported by recent Abbreviation: PCC, palliative care consultation.…”

“…Systematic integration of palliative care considerations into phase I clinical trials has the potential to improve patients' experience, as supported by recent Abbreviation: PCC, palliative care consultation. publications, [8][9][10][11][12][13][14] although this may not affect end of life outcomes for these patients. 14 We sought to determine the utilization of palliative care consultation (PCC) in pediatric phase I clinical trials by examining the prevalence of a PCC, the reason for palliative care involvement and the prescribing patterns of medications targeted toward symptom relief among oncology providers caring for these patients.…”