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

Official title

Node-Sparing Short-Course Radiation Combined With Capecitabine and PD-1/CTLA-4 for MSS Early Middle and Low Rectal Cancer (mRCAT-E): An Open-label, Single-arm, Prospective Multicenter Clinical Trial

Overview

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.

Interventions

• Radiation Lymph-node-sparing short-course radiotherapy
  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.
• Drug Capecitabine
  Oral capecitabine 1,000 mg/m² administered twice daily on Days 1-14 of each 21-day cycle, for a total of four cycles.
• Drug PD-1/CTLA-4 inhibitor (Aiparolitoworixureli injection)
  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.

Primary outcome measures

• Clinical and pathological complete response rate (CR rate) [Time frame: Up to 12 weeks after completion of chemo-immunotherapy]

Secondary outcome measures (4)

• Organ preservation rate [Time frame: 1 year after enrollment]
• 3-year local recurrence rate [Time frame: 3 years]
• Overall survival(OS） [Time frame: 3 years after chemotherapy or surgery]
• Adverse effects rate [Time frame: From date of initiation of treatment until the date of death from any cause, assessed up to 3 years]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sir run run shaw hospital — Hangzhou

Publications

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

Identifiers

NCT: NCT07068763 · SRRS-mRCAT-E

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗