Grant Number:	1R01CA311879-01 Interpret this number
Primary Investigator:	Patel, Jai
Organization:	Wake Forest University Health Sciences
Project Title:	CHAMPION-DPYD: a Community-Based Hybrid Type 2 Implementation-Effectiveness Trial of Dpyd Genotyping in Patients with Gastrointestinal Cancers
Fiscal Year:	2026

Project Summary/Abstract Genetic variations in DPYD, which encodes the key metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD), critically impair the inactivation of fluoropyrimidine (FP)-based chemotherapies, leading to substantial drug overexposure and an increased risk of severe, often life-threatening toxicity. The clinical momentum for implementing DPYD genotyping is accelerating, driven by a recent U.S. Food and Drug Administration safety announcement and updated oncology guidelines recommending consideration of pre-treatment testing prior to FP administration; however, critical gaps remain in understanding effective implementation strategies, particularly in community oncology settings – and identifying the key barriers and facilitators to adopting universal DPYD genotyping in routine clinical practice. Here, we propose the first implementation-effectiveness hybrid (type 2) trial in U.S. community oncology sites to evaluate an implementation strategy for DPYD testing. Specifically, this trial will assess the effectiveness of reducing FP-related severe toxicities and toxicity-related hospitalizations. We will conduct a cluster-randomized trial of 12 community oncology sites part of the National Cancer Institute Community Oncology Research Program. Sites will be randomized 1:1 to a "Test Only” or Test plus Implementation Strategy (“Test+IS”) group. The “Test Only” cohort will only have access to central DPYD testing, whereas the “Test+IS” group will have access to central DPYD testing plus a multicomponent implementation strategy involving targeted clinician (physicians, nurses, and pharmacists) education, central pharmacogenomics support for dosing patients with an actionable genotype, informatics support, and patient education handouts. Our first aim is to quantify the real-world uptake of pre-treatment DPYD genotyping among patients with gastrointestinal cancers initiating FP-based chemotherapy, and to evaluate adherence to pharmacogenomics guideline–concordant dose modifications among identified DPYD variant carriers. Implementation metrics will be evaluated using mixed methods and key stakeholder interviews. Aim 2 is to evaluate the clinical effectiveness of pre-treatment DPYD genotyping in reducing the incidence of severe FP-related toxicities and unplanned hospitalizations among DPYD variant allele carriers, compared to historical cohorts lacking genotype-guided dosing. Aim 3 is to assess the relative dose intensity of FP-based chemotherapy among DPYD variant allele carriers receiving genotype-guided dosing. This study is significant because it will generate critical evidence to inform clinical guideline recommendations and support the widespread adoption of DPYD testing as a standard in oncology. It is innovative as the first multisite trial to use an implementation-effectiveness hybrid design to evaluate the feasibility and clinical impact of genotype-guided FP dosing in reducing severe toxicity and hospitalization.





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