A phase 3, randomized, double-blind, placebo-controlled study of lecithinized superoxide dismutase (PC-SOD) for the prevention of chemotherapy-induced peripheral neuropathy in patients with colorectal cancer receiving adjuvant mFOLFOX6 therapy (PROSPER study).

TPS257 Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Oxaliplatin-based chemotherapy regimens, such as FOLFOX, are recognized as standard adjuvant therapy for improving survival outcomes in patients with stage II and III CRC. However, their clinical utility is often limited by chemotherapy-induced peripheral neuropathy (CIPN) that affects up to 85% of patients. CIPN seriously affects patients’ quality of life and often persists for months or even years after chemotherapy ends. In many cases, CIPN leads to dose reductions or early discontinuation of oxaliplatin, which negatively affect treatment outcomes and overall survival. Despite its clinical necessity, no pharmacologic agents have been approved for the prevention of CIPN. Lecithinized superoxide dismutase (PC-SOD) shows much longer stability in plasma than SOD, which reduces oxidative stress, one of the key mechanisms of CIPN. In rat models of oxaliplatin-induced peripheral neuropathy, PC-SOD demonstrated significant neuroprotective effects. A phase 2 clinical trial (jRCT2031210466) in CRC patients receiving adjuvant mFOLFOX6 therapy yielded promising results regarding its preventive effect on CIPN (the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2, hazard ratio (HR) 0.88; CTCAE grade ≥1, HR 0.62; Neurotoxicity Criteria of DEBIOPHARM (DEB-NTC) grade ≥2, HR 0.73) and safety. Interestingly, the study also suggested a preventive effect on oxaliplatin-induced infusion-related reactions (IRRs) (HR 0.27). Methods: This ongoing, phase 3, randomized, double-blind, placebo-controlled trial is investigating the efficacy on CIPN and safety of PC-SOD in CRC patients receiving adjuvant mFOLFOX6 therapy. Key eligibility criteria include curatively resected stage II or III colorectal adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and suitability to complete a planned 12 cycles of mFOLFOX6 at time of screening. Approximately 350 patients will be randomly assigned in a 1:1 ratio to receive mFOLFOX6 in combination with either PC-SOD or placebo. The primary endpoint is the time to onset of grade ≥2 CIPN (CTCAE), estimated using the Kaplan–Meier method and compared between groups with the log-rank test. Key secondary endpoints include the time to onset of grade ≥2 CIPN (DEB-NTC) and the incidence of grade ≥2 oxaliplatin-induced IRRs. The study is currently recruiting patients. Clinical trial information: jRCT2041250081, jRCT2031210466 .