Intra-pleural and intra-peritoneal tocilizumab therapy for managing malignant pleural effusions and ascites: The Regional Immuno-Oncology Trial (RIOT)−2 study protocol

Abstract

BackgroundMalignant pleural effusions (MPE) and malignant ascites (MA) are serious complications of advanced cancer, marked by debilitating symptoms and limited treatment options. Based on a wealth of previous literature implicating the cytokine IL-6 as a central mediator in the pathogenesis of MPE and MA, the Regional Immuno-Oncology Trial 2 (RIOT-2) clinical protocol was developed to explore intra-cavitary delivery of tocilizumab, an IL-6 receptor antagonist, as treatment for these conditions. MethodsThis phase I clinical trial (NCT 06016179) is being conducted to assess the safety and pharmacokinetics of intra-cavitary tocilizumab administration to patients with MPE and MA. Eligible patients are those with pleural effusion or peritoneal ascites due to metastatic cancer who are scheduled to undergo standard-of-care catheter placement for pleural or peritoneal drainage. Following catheter placement, patients will receive a starting dose of tocilizumab 0.5 µg/mL via intra-pleural or intra-peritoneal implantable catheters. Weekly escalating doses of tocilizumab will be given over four weeks. Primary endpoints are frequency and type of adverse events, while secondary endpoints include pharmacokinetic and immunological parameters. This single-center study will proceed until 12 patients have been treated. DiscussionInhibition of the IL-6 signaling pathway with tocilizumab is hypothesized to be a rational mitigating treatment strategy for the maladaptive intra-cavitary immune environment in patients with MPE and MA. The RIOT-2 study aims to assess the safety of intra-cavitary tocilizumab therapy, administered via indwelling catheters. Pharmacologic and translational immunologic findings generated by this study could pave the way for future research into clinical applications of intra-cavitary immunotherapy. Trial registrationThe trial is registered at ClinicalTrials.gov; NCT06016179 (registered on August 29th, 2023).