NCT06599827

Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk LARC

Neoadjuvant Moderately Hypofractionated Radiotherapy Combined with Chemotherapy and Immunotherapy for High-risk PMMR/MSS Locally Advanced Rectal Cancer: a Prospective, Exploratory Phase II Trial（iMHRT-LARC）

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Sponsor: Shanghai Zhongshan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This study aims to evaluate the effectiveness and safety of combining moderately hypofractionated radiotherapy with chemotherapy and anti-PD-1 antibodies as a neoadjuvant treatment for high-risk locally advanced rectal cancer.

Detailed description

This study investigates a novel treatment approach involving moderately hypofractionated radiotherapy (3-3.5Gy×10) combined with chemotherapy and immunotherapy for patients with high-risk locally advanced rectal adenocarcinoma, aiming to optimize treatment efficacy and patient outcomes. Neoadjuvant chemoradiotherapy followed by total mesorectal excision (TME) is the standard of care for locally advanced rectal cancer, improving surgical resection rates, local control, and sphincter preservation. Conventional long-course radiotherapy is the standard modality for neoadjuvant therapy, but it has drawbacks such as long treatment duration, high cost, and prolonged preoperative waiting time. Short-course radiotherapy, on the other hand, offers shorter treatment duration, lower cost, and shorter preoperative waiting time, but it is associated with higher rates of local recurrence. Immunotherapy has demonstrated promising anti-tumor activity in colorectal cancers with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) status, but its role in proficient mismatch repair (pMMR) and/or microsatellite stable (MSS) colorectal cancers remains unclear. However, studies have shown that the combination of chemoradiotherapy and immunotherapy can increase the pathologic complete response rate compared to chemoradiotherapy alone, suggesting that radiotherapy may serve as a stimulator of adaptive immunity and synergize with immunotherapy. Therefore, this study aims to explore the following regimen: neoadjuvant moderately hypofractionated radiotherapy at a dose of 3.5 Gy × 10 fractions to the tumors and 3 Gy × 10 fractions to the pelvic lymph node drainage area, combined with chemotherapy (capecitabine and oxaliplatin) and immunotherapy (Serplulimab). This prospective, single-center, non-randomized Phase II trial is designed to explore the efficacy and safety of the treatment regimen. Patients will receive CapeOx chemotherapy, anti-PD-1 monoclonal antibody immunotherapy, and a course of moderately hypofractionated radiotherapy. The trial protocol prioritizes safety monitoring and efficacy assessments through standardized clinical and imaging evaluations.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
RADIATION	moderately hypofractionated radiotherapy	35 Gy in 10 fractions to mesorectal and metastatic lymph nodes, and 30 Gy in 10 fractions to pelvic lymphatic drainage area, weekly over 5 days at 3-3.5 Gy/day.
DRUG	chemotherapy	CapeOx-Capecitabine 1000 mg/m² orally twice daily (days 1-14, every 21 days) + Oxaliplatin 130 mg/m² IV (day 1, every 21 days).
DRUG	immunotherapy	Serplulimab 300 mg IV infusion on day 1 every 21 days.
PROCEDURE	Total mesorectal excision (TME) surgery	Total mesorectal excision (TME) surgery assessment post 3 cycles of chemotherapy and immunotherapy; eligible patients undergo TME surgery.

Timeline

• Start date: 2024-09-20
• Primary completion: 2026-09-20
• Completion: 2029-09-20
• First posted: 2024-09-19
• Last updated: 2024-09-19

Locations

1 site across 1 country: China