RecruitingPhase 2Phase 3NCT06958432

Node-Sparing Short-Course Radiotherapy Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer (MODIFI-RC-II)

Node-Sparing Short-Course Radiotherapy Plus Sequential Chemotherapy and PD-1 Inhibitor for Mid/Low pMMR/MSS Rectal Cancer: An Open-Label, Randomized, Prospective Phase II/III Trial (MODIFI-RC-II)

Sponsor

Sixth Affiliated Hospital, Sun Yat-sen University

Enrollment

430 participants

Start Date

May 1, 2025

Study Type

INTERVENTIONAL

Conditions

Rectal Cancer Radiotherapy Neoadjuvant Therapies Immune Checkpoint Therapy

Summary

Most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) and respond poorly to PD-1 inhibitors. Radiotherapy can enhance tumor antigen release and improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes (TDLNs) are critical sites for anti-tumor immune activation, but radiation-induced damage and fibrosis may impair lymphatic drainage and immune responses. Previous studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This study aims to evaluate whether node-sparing short-course radiotherapy followed by sequential chemotherapy and PD-1 blockade can improve complete response rate in the phase II part and event-free survival in phase III part, together with sphincter preservation, treatment tolerance, and prognosis in patients with mid-low pMMR/MSS rectal cancer.

Eligibility

Min Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a combination of short-course radiation therapy, chemotherapy, and an immunotherapy drug (PD-1 inhibitor) for people with mid-to-lower rectal cancer that does not have certain genetic features (pMMR/MSS) that make it respond to immunotherapy alone. The goal is to improve how many patients can have surgery and achieve complete cancer elimination. **You may be eligible if...** - You are between 18 and 75 years old - You have been diagnosed with rectal cancer (adenocarcinoma) located in the mid or lower rectum - Your cancer is classified as pMMR or MSS (confirmed by lab testing) - Your cancer stage is T3–T4 or has spread to nearby lymph nodes, but not to distant organs - You have not yet started any treatment for this cancer - Your overall health is good (ECOG 0–1) **You may NOT be eligible if...** - Your cancer has already spread to distant organs (metastatic) - Your cancer is MSI-H or dMMR - You have had prior radiation to the pelvis - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

COMBINATION_PRODUCTNode-Sparing Radiotherapy plus Chemotherapy and PD-1 inhibitor

Patients will receive node-sparing modified short-course radiotherapy, followed by six cycles of CAPOX chemotherapy combined with a PD-1 inhibitor. After neoadjuvant treatment, patients will either undergo total mesorectal excision (TME) surgery or enter a watch-and-wait strategy based on clinical assessment.

COMBINATION_PRODUCTConventional Radiotherapy plus Chemotherapy and PD-1 inhibitor

Patients will receive conventional-target short-course radiotherapy, followed by six cycles of CAPOX chemotherapy. After neoadjuvant treatment, patients will either undergo TME surgery or enter a watch-and-wait strategy based on clinical assessment.