Abstract 89P
Background
Chronic kidney disease (CKD), defined by the KDIGO Consensus as a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 or markers of kidney damage persisting for more than three months, is prevalent in cancer patients due to factors like tumor location, drug-induced toxicities or comorbidities. Despite its high prevalence, CKD remains a frequent exclusion criterion in clinical trials due to concerns over drug pharmacokinetics and potential safety risks, limiting data on cancer treatment efficacy and safety in this population. The aim of this study was to evaluate the use of renal function-related exclusion criteria and to characterize them in early-phase oncology clinical trials.
Methods
We conducted a review of all early-phase oncology clinical trial protocols (phase 1 and 2) opened in our institution in June 2024. Renal exclusion criteria, creatinine clearance thresholds, and methods for estimating renal function were systematically analyzed. Additional data included trial type, cancer types, and therapeutic modalities. Statistical analyses explored associations between renal thresholds and trial characteristics.
Results
All 147 trial protocols included renal exclusion criteria based on creatinine clearance and/or serum creatinine. The majority of trials (98.6%) used a creatinine clearance threshold, with the most common being 50 mL/min (26%) and 60 mL/min (21%). Trials with thresholds > 45 mL/min were more likely to be phase I studies (54%, p = 0.032) or involve chemotherapy (28%, p = 0.003). There was a significant heterogeneity in renal function assessment methods: Cockcroft-Gault (C-G) was the most frequently used formula (66%), followed by MDRD (23%) and CKD-EPI (11%).
Conclusions
This study highlights the widespread reliance on outdated renal function assessment methods, particularly the C-G formula, in early-phase oncology clinical trials. Despite its limitations, C-G remains dominant. Our findings suggest a need to shift towards more precise methods such as cystatin C-based clearance, which offers better accuracy especially in cachectic patients. Adoption of modern assessment methods could improve patient safety and trial inclusivity, particularly for those with CKD.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Taiho; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Invited Speaker: Janssen, Pfizer, Janssen, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Astellas, Gilead/Immunomedics, Basilea, Taiho; Non-Financial Interests, Personal, Member: ESMO, ASCO, AACR; Non-Financial Interests, Personal, Other, scientific committee: ARC. C.P. Massard: Other, Personal, Other, Christophe Massard: Consultant/Advisory fees from Amgen, Astellas, AstraZeneca, Bayer Ipsen, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Netcancer, PegascyPrincipal/sub-Investigator of Clinical Trials for AbbVie, Aduro, Agios, Amgen, Argen-x, Astex, AstraZeneca, Aveo Pharmaceuticals, Bayer, Beigene, Blueprint, BMS, Boeringer Ingelheim, Celgene, Chugai, Clovis, Daiichi Sankyo, Debiopharm, Eisai, Eos, Exelixis, Forma, Gamamabs, Genentech, Gortec, GSK, H3 Biomedecine, Incyte, Innate Pharma, Janssen, Kura Oncology, Kyowa, Lilly, Loxo, Lysarc, Lytix Biopharma, MedImmune, Menarini, Merus, MSD, Nanobiotix, Nektar Therapeutics, Novartis, Octimet, Oncoethix, Oncopeptides AB, Orion, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Servier, Sierra Oncology, Taiho, Takeda, Tesaro, Xencor. All other authors have declared no conflicts of interest.