SCRT Based iTNT vs. LCRT Based TNT for MSS Locally Advanced Rectal Cancer

NCT07551479 | Not Yet Recruiting Phase 3

• 1 other identifier: FDRT-2025-665-4814
• Study Type: interventional
• Target: 612
• Locations: 1 country
• Sites: 1

Brief Summary

In this prospective, multicentre, randomized phase III trial, 612 locally advanced rectal cancer (LARC, T3-4/N+M0) patients with at least one high-risk features (lower location (≤5cm), cT4, cN2, MRF+, EMVI+, TD+) will be included, and randomly assigned to TNT group and iTNT group (1:1). TNT group receives long-course chemoradiotherapy (50Gy/25Fx concurrent with oral capecitabine) followed by 6 cycles of CAPOX. iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX. After the efficacy evaluation, the patients who achieves clinical complete response (cCR) will be managed by a watch and wait (W\&W) protocol and non-cCR patients will be recommended surgery. The primary endpoint is 3-year event-free survival rate (3yEFS%). The secondary endpoints include the complete response (CR, pathological complete response \[pCR\] plus cCR) rate, 3-year organ preservation rate, 3-year disease-free survival rate (3yDFS%), 3-year local recurrence free survival rate (3yLRFS%), 3-year distant metastasis free survival rate (3yDMFS%), 3-year overall survival rate (3yOS%), grade 3-4 acute adverse effects (AE) rate, rate of surgical complications, anal functions and quality of life, etc.

Conditions

MSS (Microsatellite Stable); Locally Advanced Rectal Cancer (LARC)

Keywords

Total Neoadjuvant Therapy; Immunotherapy; Survival Rate; Organ preservation; Locally advanced rectal cancer

Outcome Measures

Primary Outcomes (1)

• 3 year event-free survival rate

  Rate of 3 year event free survival

  From date of randomization until the date of first documented early local failure, disease progression during neoadjuvant therapy, pelvic recurrence, distant metastasis, or death, whichever came first, assessed up to 36 months.

Secondary Outcomes (10)

• Complete response (CR) rate

  1 month after the surgery or the decision of W&W

• 3 year organ preservation rate

  From date of randomization until the resection of rectum or anus, assessed up to 36 months.

• 3 year disease free survival rate

  From date of randomization until the date of first documented recurrence and metastasis after the completion of treatment or death from any cause, whichever came first, assessed up to 36 months.

• 3 year local recurrence free survival rate

  From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.

• 3 year distant metastasis free survival rate

  From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.

Study Arms (2)

TNT group

OTHER

TNT group receives long-course chemoradiotherapy (concurrent with oral capecitabine) followed by 6 cycles of CAPOX.

Radiation: long-course chemoradiaothearpy; Drug: Capecitabine; Drug: Oxaliplatin

iTNT group

EXPERIMENTAL

iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.

Radiation: short-course radiaotherapy; Drug: Capecitabine; Drug: Oxaliplatin; Drug: PD-1 inhibitor

Interventions

short-course radiaotherapy RADIATION

short-course radiaotherapy (25Gy/5Fx)

iTNT group

long-course chemoradiaothearpy RADIATION

long-course chemoradiotherapy (50Gy/25Fx concurrent with oral capecitabine 825mg/m2 bid d1-5 qw)

TNT group

Capecitabine DRUG

Capecitabine: 1000mg/m2 bid d1-14 q3w

TNT group; iTNT group

Oxaliplatin DRUG

Oxaliplatin 130mg/m2 d1 q3w

TNT group; iTNT group

PD-1 inhibitor DRUG

Serplulimab 300mg d1 q3w

iTNT group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old, female and male;
• Pathological confirmed adenocarcinoma;
• The distance from anal verge ≤ 10 cm;
• MSI/MMR status: MSS/pMMR;
• Clinical stage T3-4 and/or N+, without distance metastases;
• At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, positive tumor deposit or positive lateral lymph node;
• KPS ≥ 70;
• No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
• Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
• With good compliance and signed the consent form.

You may not qualify if:

• Pregnancy or breast-feeding women;
• Known history of other malignancies within 5 years;
• Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
• Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
• Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
• Uncontrolled infection which needs systemic therapy;
• Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
• Allergic to any component of the therapy.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

MeSH Terms

Conditions

Spinocerebellar Degenerations

Interventions

Capecitabine; Oxaliplatin; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Zhen Zhang, MD, PhD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 24, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2035
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)