A novel neoadjuvant regimen of chemo-immuno-embolization with transcatheter rectal arterial intervention in locally advanced rectal cancer: a study protocol for a phase II trial (CIETAI-R)

Abstract

Background Recent evidence suggests that patients with mismatch repair-deficient/microsatellite instability-high LARC are exceptionally sensitive to immune checkpoint inhibitors (ICIs), However, the majority of LARC patients are microsatellite-stable. Therefore, there is an urgent need to enhance the effectiveness of ICIs in this population. Hence, we propose a novel neoadjuvant protocol for LARC patients: chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), followed by concurrent chemoradiotherapy and programmed cell death 1 (PD-1) immunotherapy. Methods This prospective, single-arm, phase II clinical trial is designed to evaluate the effectiveness and safety of CIETAI in the management of LARC. The trial will consecutively recruit at least 37 stage II/III LARC patients from Daping hospital in China whose distal tumor are ≤ 15 cm from the anal verge. Enrolled patients will receive a sequential arterial infusion of oxaliplatin (100 mg) and PD-1 monoclonal antibody tislelizumab (200 mg) and subsequent embolization of the major rectal tumor-feeding artery using gelatin sponge particles and iodixanol. The dose of oxaliplatin was calculated according to body surface area (BSA; 130 mg/m2), of which 100 mg was infused and the remaining dose was administered intravenously. Tislelizumab will be administered intravenously every 3 weeks for an additional two cycles. Additionally, all enrolled patients will receive LCRT (45 Gy in 25 fractions: 1.8 Gy per fraction, 5 days/week), along with two 21-day cycles of capecitabine (1000 mg/m2, bid, po, day1–14). The TME surgery will be scheduled for 4 to 8 weeks after the completion of radiotherapy. Trial accrual opened on January, 2023, and scheduled to end on June, 2026. Discussion We will explore if the addition of CIETAI to chemoradiotherapy as part of neoadjuvant therapy in LARC will be safe and improve the pathological complete response rate. This study protocol is pioneering in its approach, as it introduces the administration of an anti-PD-1 antibody through tumor-feeding arteries within the neoadjuvant treatment framework, which may help reverse the immune desertification observed in LARC and their resistance to immunotherapy. Trial registration ClinicalTrials.gov Identifier: NCT05957016