Node-Sparing Short-Course Radiation Combined With Capecitabine and PD-1/CTLA-4 for MSS Early Rectal Cancer

Not Applicable

Not yet recruiting

• Conditions: Rectal Cancer
• Interventions: Radiation: Lymph-node-sparing short-course radiotherapy; Drug: Capecitabine; Drug: PD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection)

• Registration Number: NCT07068763
• Lead Sponsor: Sir Run Run Shaw Hospital

Brief Summary

This is a single-arm, prospective, multicenter study evaluating a novel neoadjuvant treatment strategy for patients with early, mid-low rectal adenocarcinoma that is microsatellite stable (MSS). Instead of irradiating regional lymph nodes, we deliver short-course radiotherapy (25 Gy in 5 fractions) exclusively to the primary tumor ("lymph-node-sparing" approach), immediately followed by four 3-week cycles of capecitabine plus combined PD-1/CTLA-4 immune checkpoint inhibitors. Two weeks after completing chemo-immunotherapy, tumor response is assessed. Patients who achieve a clinical complete response may enter a "watch-and-wait" program; others will undergo local excision or total mesorectal excision (TME) as appropriate. The primary endpoint is the rate of complete response (clinical and pathological). Secondary endpoints include organ-preservation rate, 3-year local recurrence, 3-year disease-free and overall survival, toxicity, and quality-of-life measures. Results from a pilot study suggest that this regimen may substantially improve complete response rates while reducing radiation-related toxicity, potentially allowing more patients to avoid radical surgery and permanent stoma.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-07
• Study First Submitted QC: 2025-07-07
• Study First Posted: 2025-07-16
• Last Update Submitted: 2025-07-27
• Last Update Posted: 2025-07-30
• Study Start: 2025-08-08
• Primary Completion: 2026-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

1. Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
2. Male or Female aged 18-80.
3. Patients diagnosed with low rectal cancer within 7 cm from the lower edge of the tumor to the anal verge by pelvic MRI and rectal ultrasound, the clinical stage is cT2-3N0M0.
4. Histologically confirmed rectal adenocarcinoma; Genetic testing suggests MSI-L or MSS, or tumor biopsy immunohistochemistry reveals pMMR, that is, MSH1, MSH2, MSH6, and PMS2 are all positive.
5. Eastern Cooperative Oncology Group (ECOG) score 0-1.
6. No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation).
7. Informed consent form signed.

Exclusion Criteria

1. Patients with a previous history of malignant tumors besides rectal cancer.

2. Patients with distant metastases before enrollment.

3. Patients with metastatic regional or non-regional lymph nodes are assessed by MRI or CT.

4. Patients with obstruction, perforation, or bleeding that require emergency surgery.

5. Patients with severe concomitant diseases and estimated survival time ≤ 5 years.

6. Allergic to any component of the therapy.

7. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.

8. Contraindications to radiotherapy and chemotherapy.

9. Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.

10. Factors leading to study termination, such as alcoholism, drug abuse, other serious illnesses (including psychiatric disorders) requiring combination therapy, and patients with severe laboratory abnormalities. Patients with congenital or acquired immune deficiency (such as HIV infection).

11. Vulnerable groups, including mentally ill, cognitively impaired, critically ill patients, minors, pregnant or lactating women, illiterate, etc.

    Other conditions that investigators consider not suitable for this study.

12. Patient not suitable for participating by other concerns of researchers.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental Arm	Lymph-node-sparing short-course radiotherapy	Patients receive lymph-node-sparing short-course radiotherapy of 25 Gy delivered in five daily fractions to the primary tumor bed (no nodal fields). Beginning on treatment Day 8, patients receive capecitabine 1,000 mg/m² orally twice daily on Days 1-14 plus PD-1/CTLA-4 inhibitor (5 mg/kg IV every 3 weeks) for four cycles. Tumor response is assessed 1-2 weeks after the last cycle; patients with clinical complete response enter a watch-and-wait program, while non-responders proceed to local excision or total mesorectal excision.
Experimental Arm	Capecitabine	Patients receive lymph-node-sparing short-course radiotherapy of 25 Gy delivered in five daily fractions to the primary tumor bed (no nodal fields). Beginning on treatment Day 8, patients receive capecitabine 1,000 mg/m² orally twice daily on Days 1-14 plus PD-1/CTLA-4 inhibitor (5 mg/kg IV every 3 weeks) for four cycles. Tumor response is assessed 1-2 weeks after the last cycle; patients with clinical complete response enter a watch-and-wait program, while non-responders proceed to local excision or total mesorectal excision.
Experimental Arm	PD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection)	Patients receive lymph-node-sparing short-course radiotherapy of 25 Gy delivered in five daily fractions to the primary tumor bed (no nodal fields). Beginning on treatment Day 8, patients receive capecitabine 1,000 mg/m² orally twice daily on Days 1-14 plus PD-1/CTLA-4 inhibitor (5 mg/kg IV every 3 weeks) for four cycles. Tumor response is assessed 1-2 weeks after the last cycle; patients with clinical complete response enter a watch-and-wait program, while non-responders proceed to local excision or total mesorectal excision.

Primary Outcome Measures

Name	Time	Method
Clinical and pathological complete response rate (CR rate)	Up to 12 weeks after completion of chemo-immunotherapy	Proportion of enrolled patients who achieve a clinical complete response (cCR) on imaging, endoscopy, and biopsy and/or a pathological complete response (pCR) in surgical specimens (if resected) following lymph-node-sparing short-course radiotherapy combined with capecitabine and PD-1/CTLA-4 inhibitor.

Secondary Outcome Measures

Name	Time	Method
Organ preservation rate	1 year after enrollment	Proportion of patients who avoid total mesorectal excision (TME) and permanent stoma by remaining in watch-and-wait or undergoing only local excision.
3-year local recurrence rate	3 years	Proportion with tumor recurrence in the pelvis
Overall survival(OS）	3 years after chemotherapy or surgery	The three-year overall survival of patients.
Adverse effects rate	From date of initiation of treatment until the date of death from any cause, assessed up to 3 years	Rate of radiotherapy, chemotherapy and immunotherapy related adverse events