SCRT Based iTNT vs. LCRT Based TNT for MSS Locally Advanced Rectal Cancer (TORCH-STAR)

SCRT Followed by CAPOX and PD-1 Inhibitor Versus LCCRT Followed by CAPOX in Total Neoadjuvant Treatment for High-risk LARC: A Prospective, Randomized, Multicenter, Phase III Study

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Rectal Cancer (LARC); MSS (Microsatellite Stable)
• Intervention / Treatment: Drug: Capecitabine; Drug: Oxaliplatin; Radiation: long-course chemoradiaothearpy; Radiation: short-course radiaotherapy; Drug: PD-1 inhibitor

• Study Type: Interventional
• Enrollment (Estimated): 612
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhen Zhang, MD, PhD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Zhen Zhang, MD, PhD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn
    • Contact: Yaqi Wang, MD; Phone Number: 18121299593; Email: 10301010093@fudan.edu.cn
    • Principal Investigator: Zhen Zhang, MD PhD
    • Principal Investigator: Xinxiang Li, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age 18-75 years old, female and male;
2. Pathological confirmed adenocarcinoma;
3. The distance from anal verge ≤ 10 cm;
4. MSI/MMR status: MSS/pMMR;
5. Clinical stage T3-4 and/or N+, without distance metastases;
6. 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;
7. KPS ≥ 70;
8. No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
9. 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;
10. With good compliance and signed the consent form.

Exclusion Criteria

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: TNT group; TNT group receives long-course chemoradiotherapy (concurrent with oral capecitabine) followed by 6 cycles of CAPOX.	Drug: Capecitabine; Capecitabine: 1000mg/m2 bid d1-14 q3w; Drug: Oxaliplatin; Oxaliplatin 130mg/m2 d1 q3w; Radiation: long-course chemoradiaothearpy; long-course chemoradiotherapy (50Gy/25Fx concurrent with oral capecitabine 825mg/m2 bid d1-5 qw)
Experimental: iTNT group; iTNT group receives short-course radiotherapy (25Gy/5Fx) followed by 6 cycles of Serplulimab combined with CAPOX.	Drug: Capecitabine; Capecitabine: 1000mg/m2 bid d1-14 q3w; Drug: Oxaliplatin; Oxaliplatin 130mg/m2 d1 q3w; Radiation: short-course radiaotherapy; short-course radiaotherapy (25Gy/5Fx); Drug: PD-1 inhibitor; Serplulimab 300mg d1 q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year overall survival rate	Rate of 3 year overall survival	From date of randomization until the date of death from any cause, assessed up to 36 months.
3 year local recurrence free survival rate	Rate of 3 year local recurrence free survival	From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.
Complete response (CR) rate	Rate of complete response (CR), including the rate of pathologic complete response (pCR) after surgery and the rate of cCR with W&W strategy.	1 month after the surgery or the decision of W&W
Grade 3-4 adverse effects rate	Rate of chemotherapy, radiotherapy and immunotherapy related adverse events	From date of randomization until 3 months after the completion neoadjuvant therapy
3 year distant metastasis free survival rate	Rate of 3 year distant metastasis free survival	From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.
3 year organ preservation rate	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	Rate of 3 year disease free survival	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.
Rate of surgical complications	Rate of surgical complications	The surgical complications were assessed within 1 year after the surgery.
Low Anterior Resection Syndrome Score	Evaluating the anal function using Low Anterior Resection Syndrome (LARS) score（range 0-42, with higher scores representing worse anal function）	From date of randomization until five years after the completion of treament.
Wexner Continence Grading Scale	Evaluating the anal function using Wexner Continence Grading Scale (range 1-20, with higher scores representing worse anal function)	From date of randomization until five years after the completion of treament.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2032
• Study Completion (Estimated): December 31, 2035

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Locally advanced rectal cancer; Organ preservation; Total Neoadjuvant Therapy; Survival Rate
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Cerebellar Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinocerebellar Degenerations; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Immune Checkpoint Inhibitors
• Other Study ID Numbers: FDRT-2025-665-4814

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No