Long-course versus short-course radiotherapy before immunotherapy and total neoadjuvant therapy for locally advanced rectal cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a national, multicenter, randomized, placebo-controlled Phase III trial comparing TNT combined with immunotherapy to a conventional long-course radiotherapy followed by TNT approach, and also comparing short-course versus long-course radiotherapy within the TNT-plus-immunotherapy strategy. Eligible patients with pMMR/MSS locally advanced rectal adenocarcinoma are randomized to receive radiotherapy (short- or long-course) plus standard chemotherapy (capecitabine and oxaliplatin) with or without the investigational immunotherapy agent HLX10. The trial incorporates dynamic minimal residual disease (MRD) monitoring for precision management of patients with clinical complete response, including baseline and follow-up testing for tumors ≤5 cm from the anal verge. Primary comparisons focus on efficacy and toxicity between the radiotherapy schedules and on whether adding immunotherapy to TNT improves outcomes compared with historical long-course RT followed by TNT.

Why it matters

Who can join: the full rules

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. Immunohistochemistry and/or genetic testing confirmed pMMR/MSS;
5. inferior margin ≤ 10 cm from the anal verge;
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 MSI-H/dMMR 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).

Where it's running

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  Wuhan, Hubei, China Recruiting

Study contacts

• Principal investigator: Zhenyu Lin, MD — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Zhenyu Lin, MD
• Email: whxhlzy@hust.edu.cn
• Phone: 027-85871982

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.