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

Official title

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

Overview

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.

Interventions

• Radiation short-course radiaotherapy
  short-course radiaotherapy (25Gy/5Fx)
• Radiation long-course chemoradiaothearpy
  long-course chemoradiotherapy (50Gy/25Fx concurrent with oral capecitabine 825mg/m2 bid d1-5 qw)
• Drug Capecitabine
  Capecitabine: 1000mg/m2 bid d1-14 q3w
• Drug Oxaliplatin
  Oxaliplatin 130mg/m2 d1 q3w
• Drug PD-1 inhibitor
  Serplulimab 300mg d1 q3w

Primary outcome measures

• 3 year event-free survival rate [Time frame: 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 (10)

• Complete response (CR) rate [Time frame: 1 month after the surgery or the decision of W&W]
• 3 year organ preservation rate [Time frame: From date of randomization until the resection of rectum or anus, assessed up to 36 months.]
• 3 year disease free survival rate [Time frame: 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 [Time frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.]
• 3 year distant metastasis free survival rate [Time frame: From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.]
• 3 year overall survival rate [Time frame: From date of randomization until the date of death from any cause, assessed up to 36 months.]
• Grade 3-4 adverse effects rate [Time frame: From date of randomization until 3 months after the completion neoadjuvant therapy]
• Rate of surgical complications [Time frame: The surgical complications were assessed within 1 year after the surgery.]
• Low Anterior Resection Syndrome Score [Time frame: From date of randomization until five years after the completion of treament.]
• Wexner Continence Grading Scale [Time frame: From date of randomization until five years after the completion of treament.]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT07551479 · FDRT-2025-665-4814

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗