Use of modernized eligibility criteria in pancreatic cancer clinical trials.
Authors: Riner Andrea N , Freudenberger Devon Clemons , Herremans Kelly M , Neal Daniel W , Vudatha Vignesh , George Thomas J. , Trevino Jose G 
Published: June 2022

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Background: In 2017, ASCO + Friends recommended modernized eligibility criteria to improve generalizability of clinical trial results. Traditional criteria contribute to disparities in trial participation, yet modernized criteria can equalize eligibility rates. We aimed to assess use of modernized eligibility criteria in pancreatic ductal adenocarcinoma (PDAC) clinical trials since the updated guidelines. Methods: Modernized eligibility criteria were obtained from ASCO + Friends guidelines. Clinicaltrials.gov was queried for “pancreas adenocarcinoma” trials from Jan. 1, 2018 onward and eligibility criteria were assessed for compliance with modernized criteria. Kruskal-Wallis and Fisher’s exact tests were used to determine differences in compliance based on disease stage(s), starting year, phase, and funder. Results: In total, 108 clinical trials were identified - 31.5% for resectable, 56.5% for unresectable, 12.0% for both resectable/unresectable disease. Most trials were phase 1 (24.1%), phase 1|2 (15.7%) or phase 2 (45.4%). Funding sources included industry (38.0%), NIH (22.2%) and other sources (39.8%). No trial was compliant with all modernized criteria. Only 34.7% of trials allowed patients with ECOG performance status of 2. HIV+ patients were not allowed in 56.5% of trials. Only 7 trials (6.5%) were compliant with assessing renal function whereas 64.8% appropriately used upper limit of normal cutoffs for labs. Among trials that excluded patients for CHF, 59.6% used a classification system for exclusion. Specific cardiac abnormalities were excluded in 60.2% of trials. Prior malignancy was allowed in 71.3% of trials if treated > 2 years prior and concurrent malignancy, if stable, was allowed in 21.3% of trials. Prior PDAC treatment was allowed for 38.0% and required for 24.1% of trials. If prior treatment was allowed, 94% justified drug exclusions, 40.3% did not require a washout period, and 35.8% required recovery from prior adverse events. Stable/treated brain metastases were allowed in 33.8% of trials for unresectable cancer. Compliance with prior malignancy criteria improved from 2018-2019 to 2020-2022 (56.0% vs 84.5%, respectively; p = 0.001). Requirement of prior PDAC treatment was associated with disease stage (8.8% for resectable, 32.8% for unresectable, and 23.1% for both; p = 0.024), as was exclusion based on prior therapy (58.8% for resectable disease, 14.8% for unresectable, and 30.8% for both; p < 0.0001). Earlier trial phase was associated with prior treatment allowance (p = 0.002), whereas later phase trials were less likely to allow prior treatment (p = 0.021). NIH-funded trials required prior treatment (37.5%) more than industry (29.3%) or other (11.6%) funded trials (p = 0.034). Conclusions: Modernized eligibility criteria are inadequately implemented in PDAC clinical trials. Efforts to improve their use are warranted to produce more generalizable results and advance inclusivity.