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

NCT07068763 | Recruiting Phase 2 DMC

• 1 other identifier: SRRS-mRCAT-E
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Rectal Cancer

Keywords

lymph-node-sparing short-course radiotherapy; capecitabine; PD-1 inhibitor; CTLA-4 inhibitor; organ preservation; clinical complete response

Outcome Measures

Primary Outcomes (1)

• Clinical and pathological complete response rate (CR rate)

  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.

  Up to 12 weeks after completion of chemo-immunotherapy

Secondary Outcomes (4)

• Organ preservation rate

  1 year after enrollment

• 3-year local recurrence rate

  3 years

• Overall survival(OS）

  3 years after chemotherapy or surgery

• Adverse effects rate

  From date of initiation of treatment until the date of death from any cause, assessed up to 3 years

Study Arms (1)

Experimental Arm

EXPERIMENTAL

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.

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

Interventions

Lymph-node-sparing short-course radiotherapy RADIATION

Three-dimensional conformal or intensity-modulated radiotherapy targeting only the primary tumor bed (no regional lymph nodes), delivering a total dose of 25 Gy in 5 Gy fractions over five consecutive days.

Experimental Arm

Capecitabine DRUG

Oral capecitabine 1,000 mg/m² administered twice daily on Days 1-14 of each 21-day cycle, for a total of four cycles.

Experimental Arm

PD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection) DRUG

Intravenous PD-1/CTLA-4 bispecific monoclonal antibody at 5 mg/kg every 3 weeks for four cycles, starting on Day 8 after completion of radiotherapy.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who have a strong willingness to preserve the anus and are willing to receive neoadjuvant therapy.
• Male or Female aged 18-80.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) score 0-1.
• No previous treatment (including anti-tumor therapy, immunotherapy or pelvic radiation).
• Informed consent form signed.

You may not qualify if:

• Patients with a previous history of malignant tumors besides rectal cancer.
• Patients with distant metastases before enrollment.
• Patients with metastatic regional or non-regional lymph nodes are assessed by MRI or CT.
• Patients with obstruction, perforation, or bleeding that require emergency surgery.
• Patients with severe concomitant diseases and estimated survival time ≤ 5 years.
• Allergic to any component of the therapy.
• Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of therapy.
• Contraindications to radiotherapy and chemotherapy.
• Patients who have received any other experimental drug (including immunotherapy) or participated in another interventional clinical trial within 30 days before screening.
• 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).
• 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.
• Patient not suitable for participating by other concerns of researchers.

Sponsors & Collaborators

• Sir Run Run Shaw Hospital: lead

Study Sites (1)

Sir run run shaw hospital

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (3)

• Lezoche E, Guerrieri M, Paganini AM, D'Ambrosio G, Baldarelli M, Lezoche G, Feliciotti F, De Sanctis A. Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low rectal cancers after neoadjuvant treatment: a prospective randomized trial with a 3-years minimum follow-up period. Surg Endosc. 2005 Jun;19(6):751-6. doi: 10.1007/s00464-004-8930-x. Epub 2005 May 4.

  PMID: 15868260 RESULT

• Annals of Oncology (2024) 24 (suppl_1): 1-20. 10.1016/iotech/iotech100744

  RESULT

• Habr-Gama A, Perez RO, Wynn G, Marks J, Kessler H, Gama-Rodrigues J. Complete clinical response after neoadjuvant chemoradiation therapy for distal rectal cancer: characterization of clinical and endoscopic findings for standardization. Dis Colon Rectum. 2010 Dec;53(12):1692-8. doi: 10.1007/DCR.0b013e3181f42b89.

  PMID: 21178866 RESULT

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Bingjun Bai, MD

CONTACT

8613858816897; echobai@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice president

Model Details: Single-arm, open-label trial

Study Record Dates

• First Submitted: July 7, 2025
• First Posted: July 16, 2025
• Study Start: October 9, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

CN (1)