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

Tao Zhang

Status and phase: Not yet enrolling; Phase 3

Conditions: Total Neoadjuvant Therapy; Immunotherapy; Radiotherapy; Rectal Cancer

Treatments: Drug: Capecitabine; Drug: Camrelizumab; Drug: Oxaliplatin; Radiation: Long-course radiotherapy; Radiation: Short-course radiotherapy; Procedure: TME surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT07113275

XHZDZLK

Details and patient eligibility

About

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.

Full 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.

Enrollment: 435 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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435 participants in 3 patient groups

Group A: SCRT + iTNT

Experimental group

Description:

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.

Treatment:

Procedure: TME surgery

Drug: Oxaliplatin

Radiation: Short-course radiotherapy

Drug: Camrelizumab

Drug: Capecitabine

Group B: LCRT + iTNT

Experimental group

Description:

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.

Treatment:

Procedure: TME surgery

Drug: Oxaliplatin

Radiation: Long-course radiotherapy

Drug: Camrelizumab

Drug: Capecitabine

Group C: LCRT + TNT

Active Comparator group

Description:

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.

Treatment:

Procedure: TME surgery

Drug: Oxaliplatin

Radiation: Long-course radiotherapy

Drug: Capecitabine