Purpose: Clinical trials (CTs) in proton beam therapy (PBT) are important for determining its benefits relative to other treatments. An analysis of PBT trials is, thus, warranted to understand the current state of PBT CTs and the factors affecting current and future trials. Materials and Methods: We queried the clinicaltrials.gov Website using the search terms: proton beam therapy, proton radiation, and protons. A total of 152 PBT CTs were identified. We used χ2 analysis and logistic regression to evaluate trial characteristics. Results: Most CTs were recruiting (n = 79; 52.0%), phase II (n = 95; 62.5%), open label (n = 134; 88.2%), single-group assignment (n = 84; 55.3%), and with primary treatment endpoints of safety and efficacy (n = 94; 61.8%). The primary treatment sites included gastrointestinal (n = 32; 21.1%), central nervous system (n = 31; 20.4%), lung (n = 21; 13.8%), prostate (n = 19; 12.5%), sarcoma (n = 15; 9.9%), and others (n = 24; 15.8%). Comparison studies between radiation modalities involved PBT and intensity-modulated photon therapy (n = 11; 7.2%), PBT and general photon therapy (n = 8; 5.3%), and PBT and carbon-ion therapy (n = 7; 4.6%). The PBT CTs underwent substantial growth after 2008 but now appear to be in decline. Nongovernmental institutions, comprising university centers, hospital systems, and research groups, have funded the greatest number of CTs (n= 106; 69.7%). The National Institutes of Health (NIH) were more likely to fund CTs involving the central nervous system ( P = 0.02). Trials involving NIH funding were more likely to result in successful trial completion ( P = 0.02). Conclusion: Among PBT CTs, most were phase II trials, with a very few being phase III CTs. Funding of PBT CTs originating from industry or the NIH is limited. Recently, there has been a declining trajectory of newly initiated PBT trials. It is not yet clear whether this represents a true trend or just a pause in CT implementation. Despite multiple impediments to PBT CTs, the particle therapy community continues to work toward evidence generation.
A 20-Year Analysis of Clinical Trials Involving Proton Beam Therapy