A Clinical Trial Comparing Long-Course Versus Short-Course Radiotherapy Followed by Immunotherapy Combined With Total Neoadjuvant Therapy (TNT) to Long-Course Radiotherapy Followed by TNT in High-Risk Locally Advanced Rectal Cancer

Launched by TAO ZHANG · Aug 2, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new approach to treating high-risk, locally advanced rectal cancer. Researchers want to see if combining immunotherapy—a treatment that helps the immune system fight cancer—with a type of chemotherapy given before surgery, called total neoadjuvant therapy (TNT), works better when paired with either a shorter or longer course of radiation treatment. The goal is to find out which radiation plan, followed by immunotherapy and chemotherapy, helps patients the most.

People who might join this study are adults between 18 and 75 years old who have a certain type of rectal cancer that is considered high-risk based on detailed imaging tests. Participants must not have had previous cancer treatments like chemotherapy, radiation, or surgery for their rectal cancer. If they join, patients will receive either a short or long course of radiation therapy, followed by immunotherapy combined with chemotherapy before surgery. The study aims to understand which treatment plan is safer and more effective, helping doctors improve care for patients with this type of cancer.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patients or their family members agree to participate in the study and sign the informed consent form;
• • 2. Age 18-75 years, male or female;
• • 3. Histologically confirmed Locally Advanced rectal adenocarcinoma
• • 4. inferior margin ≤ 10 cm from the anal verge;
• • 5. Pelvic MRI shows high risk \[meets one of the following conditions\]: • Clinical tumor (cT) staging cT4a or cT4b (according to AJCC 8th Edition) • Extramural vascular infiltration • Clinical lymph node (cN) staging cN2 (according to AJCC 8th Edition) • Mesenteric fascia is involved • Lateral lymph node enlargement
• • 6. ECOG performance status score is 0-1;
• • 7. Untreated with anti-tumor therapy for rectal cancer, including radiotherapy, chemotherapy, surgery, etc;
• • 8. There was no operative contraindication;
• • 9. Laboratory tests were required to meet the following requirements: white blood cell (WBC) ≥ 4×109/L; Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelet count ≥ 100×109/L; Hemoglobin ≥90 g/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Serum creatinine ≤1.5 times the upper limit of normal value or creatinine clearance rate ≥50 mL/min; International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
• • 10. Urinary protein \< 2+ or 24-hour urinary protein excretion \< 1 g at baseline.
• Exclusion Criteria:
• • 1. Patients with non-high-risk pMMR LARC；
• • 2. Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
• • 3. Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).