Abstract Background While care delivery trials to integrate early palliative care in community oncology practices are needed to enhance guideline-concordant care, little is known about how to successfully implement these trials within national research networks. Methods A process evaluation was conducted to identify and address practice and patient recruitment challenges within a nationwide cluster randomized trial testing two implementation strategies (virtual learning collaborative vs technical assistance) for integrating the Educate, Nurture, Advise, Before Life Ends (ENABLE) early palliative care program in the National Cancer Institute Community Oncology Research Program (NCORP). To examine implementation barriers, we collected quantitative practice and clinician characteristics via surveys and conducted qualitative interviews with clinicians and staff. Interview data were coded and summarized using content analyses to identify barriers to implementing study procedures and the ENABLE program. Results Surveys and interviews were completed by 33 clinicians, 23 ENABLE coaches, and 19 coordinators in 9 practice clusters between April 2021 and June 2022. Although 78% of practice clusters identified availability of some palliative care services, none routinely referred all newly diagnosed advanced cancer patients to these services as recommended by guidelines. Key research and clinical ENABLE implementation barriers included: limited staffing during and after COVID-19, low physician buy-in, belief that ENABLE overlapped with existing palliative services, and participant burden. In response, several trial modifications were made to enhance flexibility with study procedures and the clinical ENABLE intervention. Conclusions Implementation trials within cancer clinical trial networks must employ pragmatic and iterative study procedures to accommodate clinical practice workflows. Trial Registration ClinicalTrials.gov Identifier: NCT04062552
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