Voices of children and adolescents with incurable cancer on Phase I or II Trials

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DESCRIPTION (provided by applicant): In the United States, cancer is the number one disease-related cause of death in children between the ages of 1 and 19 years; approximately 25% of the 12,400 children newly diagnosed with cancer will die of their disease. A priority of the National Institute of Nursing Research and the National Cancer Institute is to improve the quality of life of pediatric cancer patients at end of life in part by measuring patient- reported outcomes (PROs). Inviting and measuring the pediatric cancer patients' symptom and quality of life reports when their disease is incurable will help clinicians to anticipate and better manage their symptoms secondary to cancer and reduce patient suffering. PROs are included in multiple Phase III therapeutic trials where the objective is cure. No PRO is a component of pediatric Phase I (drug dose finding and toxicity) or Phase II (drug activity and safety) trials, yet it is these two trial types that contribute to new drug indications and labeling. Quite recently, the U.S. Food and Drug Administration (FDA) has released guidance concerning the use of PROs in trials to support drug labeling, including clear language requiring PROs in pediatrics and not parent or clinician proxy reports. To date, no pediatric oncology drug indication has been secured on the basis of a PRO; organ and system toxicities are documented but not the child's voice in terms of symptom and QoL experiences while enrolled on the experimental drug trial. We now have pediatric instrumentation to measure symptoms and aspects of quality of life (QoL) by patient report in 8 to 18 year olds, developed and validated as part of the PROMIS (Patient-Reported Outcomes Measurement Information System) initiative sponsored by the NIH Roadmap for Medical Research. These instruments combined with an interview will allow us to go beyond the single traditionally measured benefit (tumor response) of Phase I or Phase II participation by children and adolescents with incurable cancer to documenting their symptoms and QoL during this phase of care. With these tools to measure pediatric PROs, we will provide knowledge to help clinicians diminish patient suffering and we could position pediatric oncology to meet FDA standards for drug labeling and in this two-site, longitudinal validity study (T1, time of trial enrollment; T2, 3 to 4 weeks later), we will assess the feasibility, acceptability, reliability, validity and responsiveness of the PROMIS pediatric instruments for the first time ever in up to 80, 8 to 18 year olds with incurable or refractory cancer enrolled on Phase I or Phase II trials. PUBLIC HEALTH RELEVANCE: Children and adolescents with incurable cancer can receive experimental drugs that cause them troubling symptoms. Clinicians could better manage these symptoms and reduce patient suffering if the troubling symptoms were measured directly in reports from these young patients. This study will allow us to measure direct symptom and quality of life reports of children and adolescents with incurable cancer who are receiving experimental drugs.