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RecruitingNCT07113275Updated May 13, 2026

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 Locally Advanced Rectal Cancer

A Phase 3 interventional study of Short-course radiotherapy and Long-course radiotherapy in Rectal Cancer, Total Neoadjuvant Therapy and Radiotherapy, sponsored by Tao Zhang. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-05-13.

Sponsored by Tao Zhang · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
444
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This study is a national multicenter, prospective randomized, placebo- controlled Phase III clinical trial designed to investigate the potential therapeutic benefit of immunotherapy combined with total neoadjuvant therapy (TNT) and to compare the efficacy of different radiotherapy modalities followed by immunotherapy.

Read the detailed description

This study is a national multicenter, prospective randomized, placebo- controlled phase III clinical trial, with the following objectives: 1. For patients with LARC, to determine whether the efficacy of TNT combined with immunotherapy is superior to that of the treatment mode of LCRT followed by TNT; 2. To compare the differences in efficacy and toxicity between long-course radiotherapy and short-course radiotherapy under the mode of TNT combined with immunotherapy.

For precision management of patients with cCR post-neoadjuvant therapy, dynamic MRD monitoring was implemented, including baseline and follow-up testing for patients having tumors ≤5 cm from the anal verge.

02

Conditions studied

  • Rectal Cancer
  • Total Neoadjuvant Therapy
  • Radiotherapy
  • Immunotherapy

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03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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).
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
444 participants (estimated)

Study arms

  • Experimental
    Group A: SCRT + iTNT

    Group A: SCRT + iTNT Radiotherapy (SCRT): Total dose 25 Gy delivered in 5 fractions (5 Gy per fraction, once daily over 5 consecutive days). Immunotherapy (HLX10): 300 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion. Chemotherapy (CAPEOX regimen): Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

    Radiation: Short-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Drug: HLX10 · Procedure: TME surgery

  • Experimental
    Group B: LCRT + iTNT

    Group B: LCRT + iTNT Radiotherapy with Concurrent Chemotherapy (LCRT): Total dose 50.4 Gy delivered in 28 fractions (1.8 Gy per fraction, once daily, 5 days per week). Concurrent Capecitabine: 825 mg/m² orally twice daily, 5 days per week (administered on radiotherapy days). Immunotherapy (HLX10): 300 mg IV infusion q3w for 6 cycles, initiated 2 weeks after radiotherapy completion. Chemotherapy (CAPEOX regimen): Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; initiated 2 weeks post-radiotherapy; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

    Radiation: Long-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Drug: HLX10 · Procedure: TME surgery

  • Active comparator
    Group C: LCRT + TNT

    Group C: LCRT + TNT Radiotherapy with Concurrent Chemotherapy (LCRT): Total dose 50.4 Gy delivered in 28 fractions (1.8 Gy per fraction, once daily, 5 days per week). Concurrent Capecitabine: 825 mg/m² orally twice daily, 5 days per week (administered on radiotherapy days). TNT Chemotherapy (CAPEOX regimen) with immunotherapy placebo: HLX10 placebo: 300 mg IV infusion q3w for 6 cycles, initiated 2 weeks after radiotherapy completion. Oxaliplatin: 130 mg/m² IV infusion over 120 minutes on Day 1. Capecitabine: 1000 mg/m² orally twice daily (morning and evening, 30 minutes after meals) on Days 1-14. Cycle duration: 3 weeks per cycle; initiated 2 weeks post-radiotherapy; total of 6 cycles during the neoadjuvant phase. Then followed by a total mesorectal excision(TME) or Watch \& Wait strategy for clinical complete remission voluntary patients.

    Radiation: Long-course radiotherapy · Drug: Capecitabine · Drug: Oxaliplatin · Procedure: TME surgery · Drug: HLX10 placebo

Interventions

  • RadiationShort-course radiotherapy

    Eligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.

    Also known as: SCRT

  • RadiationLong-course radiotherapy

    Long-course radiotherapy (LCRT, 50.4 Gy administered in 28 fractions) will be delivered concurrently with oral capecitabine.

  • DrugCapecitabine

    1000mg/m2, bid, po, d1-14,q3w

  • DrugOxaliplatin

    130mg/m2, ivgtt, d1,q3w

  • DrugHLX10

    300mg, ivgtt, q3w

  • ProcedureTME surgery

    The surgery was performed 1 week after the end of neoadjuvant therapy.

  • DrugHLX10 placebo

    300mg, ivgtt, q3w

05

What researchers measure

Primary outcomes

  1. 3-year event-Free Survival

    The time from the start of treatment to the occurrence of any of the following events, which ever occurs first: tumor disease progression on imaging as assessed by RECIST 1.1; tumor recurrence, including local recurrence or distant recurrence, as assessed on imaging or tissue biopsy transfer; death from any cause

    Time frame: an expected average of 3 years

Secondary outcomes

  1. complete response (CR) rate

    Defined as pathological complete response (pCR) + Clinical complete response (cCR)

    Time frame: an expected average of 12 months

  2. Overall Survival

    The time from the date of randomization to the death caused by any cause

    Time frame: an expected average of 5 years

  3. Adverse events (AEs) were graded according to the NCI CTCAE version 5·0

    Adverse events and surgical safety

    Time frame: an expected average of 1.5 years

06

Study locations

1 of 1 sites recruiting
  • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
    Wuhan, Hubei 430022, China
    Recruiting
07

Registry details

Key details

Study ID
NCT07113275
Lead sponsor
Tao Zhang
Responsible party
Tao Zhang (MD, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) — Sponsor-investigator
First posted
Aug 8, 2025
Start date
May 15, 2026 (estimated)
Primary completion
Jan 1, 2028 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
May 13, 2026

Study contacts

Zhenyu Lin, MD
Contact
whxhlzy@hust.edu.cn
027-85871982
Tao Zhang, MD
Contact
Zhenyu Lin, MD
principal investigator · Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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