A systematic review of eligibility criteria for phase II clinical trials for patients with lung cancer


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Gary Doherty1,Innocent Ogunmwonyi2,Rohan Shotton1
1Cambridge University Hospitals NHS Foundation Trust,2University of Cambridge

Abstract

Background

Significant barriers exist for the successful enrolment of Oncology patients in early phase clinical trials. These include restrictive eligibility criteria that often exclude patients with intracranial disease, abnormal organ function or laboratory tests, and particular co-morbidities. To investigate these further, we performed a systematic review of the eligibility criteria in recent phase II clinical trials for patients with lung cancer.

Method

We searched the clinicaltrials.gov database for trials registered in 2016 using the criteria “lung cancer” and “phase 2.” 223 trials were identified. Duplicate/incomplete entries, and those not investigating systemic anti-cancer agents, were excluded. Eligibility criteria were then determined for the remaining 173 trials. Results were matched against known pharmacokinetic/toxicity data for the relevant agents, trial outcomes, sponsorship type, and country. Further analyses were performed to determine temporal trends.

Results

Common eligibility criteria were highly variable. Highly significant variability existed for the exclusion of patients with liver function derangement (used in 79.2%; 12.7% even without known hepatic drug metabolism/hepatotoxicity), renal function derangement (used in 79.2%; 14.5% even without known renal drug clearance/nephrotoxicity), low blood cell/haemoglobin counts (used in 78.6%), or coagulation abnormalities (used in 16.8%). Wide ranges of cut-offs and methodologies were used to determine eligibility. While 89.6% of trials permitted patients with brain metastases, 41.2% of these excluded patients taking concomitant corticosteroids. Successfully suppressed HIV/HepB/HepC was permitted in 41.6, 82.7% and 81.5%, respectively. Comprehensive eligibility criteria analyses, pairwise correlations with drug metabolism/toxicities, temporal trends, and correlation between eligibility restrictiveness and trial outcomes, will be presented.

Conclusion

The safety of patients participating in clinical trials is paramount. However, our results suggest that the significant variability in eligibility criteria cannot be wholly explained by a priori knowledge of the investigational agents’ metabolism and known toxicities, which may lead to irrational and unjustifiable exclusion of patients in a high-need population from access to experimental therapies.