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

NCT ID: NCT07113275

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2028-12-31

Brief Summary

This study is a national multicenter, prospective randomized 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.

Detailed Description

This study is a national multicenter, prospective randomized controlled phase III clinical trial, with the following objectives: 1. For patients with high-risk 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.

Conditions

Rectal Cancer; Total Neoadjuvant Therapy; Radiotherapy; Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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 (Camrelizumab): 200 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.

Group Type: EXPERIMENTAL

Short-course radiotherapy

Intervention Type: RADIATION

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

Capecitabine

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

130mg/m2, ivgtt, d1,q3w

Camrelizumab

Intervention Type: DRUG

200mg, ivgtt, q3w

TME surgery

Intervention Type: PROCEDURE

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

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 (Camrelizumab): 200 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.

Group Type: EXPERIMENTAL

Long-course radiotherapy

Intervention Type: RADIATION

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

Capecitabine

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

130mg/m2, ivgtt, d1,q3w

Camrelizumab

Intervention Type: DRUG

200mg, ivgtt, q3w

TME surgery

Intervention Type: PROCEDURE

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

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, without immunotherapy):

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.

Group Type: ACTIVE_COMPARATOR

Long-course radiotherapy

Intervention Type: RADIATION

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

Capecitabine

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

130mg/m2, ivgtt, d1,q3w

TME surgery

Intervention Type: PROCEDURE

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

Interventions

Short-course radiotherapy

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

Intervention Type: RADIATION

Long-course radiotherapy

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

Intervention Type: RADIATION

Capecitabine

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

Intervention Type: DRUG

Oxaliplatin

130mg/m2, ivgtt, d1,q3w

Intervention Type: DRUG

Camrelizumab

200mg, ivgtt, q3w

Intervention Type: DRUG

TME surgery

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

Intervention Type: PROCEDURE

Other Intervention Names

SCRT

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tao Zhang

OTHER

Sponsor Role: lead

Responsible Party

Tao Zhang

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zhenyu Lin, MD

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Countries

China

Central Contacts

Zhenyu Lin, MD

Role: CONTACT

whxhlzy@hust.edu.cn

027-85871982

Tao Zhang, MD

Role: CONTACT

Facility Contacts

Tao Zhang, MD

Role: primary

1277577866@qq.com

027-85871982

Other Identifiers

XHZDZLK

Identifier Type: -

Identifier Source: org_study_id