SCRT Followed by CAPOX + Bev ± PD-1 Inhibitor for TNT in LARC

NCT07198165 | Recruiting Phase 2

• 1 other identifier: TRAINER-2
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.

Conditions

Rectal Cancer; Rectal Adenocarcinoma; Rectal Cancer, Radiotherapy; Rectal Cancer Patients; Immunotherapy; Total Neoadjuvant Therapy; Total Neoadjuvant Treatment; Targeted Therapy; Chemoradiotherapy

Keywords

Rectal cancer; Total Neoadjuvant Therapy; Immunotherapy; Targeted therapy; Chemoradiotherapy

Outcome Measures

Primary Outcomes (1)

• Complete Response rate

  Measurement Methods: Chi-square test, Fisher's exact test, multivariate regression analysis (Cox regression model). Description: For pCR and cCR, chi-square test or Fisher's exact test was used to compare differences between the two groups. Multivariate regression analysis (Cox regression model) was employed to assess the relationship between the intervention and the CR rate.

  2 weeks after the surgery

Secondary Outcomes (7)

• Disease-Free Survival (DFS)

  from enrollment to the end of follow-up at 48 months

• Distant Metastasis Rate

  from enrollment to the end of follow-up at 48 months

• Local Recurrence Rate

  from enrollment to the end of follow-up at 48 months

• Overall Survival (OS)

  from enrollment to the end of follow-up at 48 months

• Pathological Stage

  2 weeks after the surgery

Study Arms (2)

Control group

NO INTERVENTION

Short-course radiotherapy (25Gy/5Fx) followed by 4 cycles of CAPOX regimen (Oxaliplatin 130mg/m² IV infusion, Capecitabine 1000mg/m² orally for 14 days, Q3w) combined with Bevacizumab (7.5mg/kg IV infusion, D1, Q3w) .Following completion of total neoadjuvant therapy, the treatment strategy (watch-and-wait or surgical resection) will be selected based on tumor response. The decision regarding adjuvant chemotherapy will be determined according to postoperative pathological findings.

Intervention group

EXPERIMENTAL

Short-course radiotherapy (25Gy/5Fx) followed by 4 cycles of CAPOX regimen (Oxaliplatin 130mg/m² IV infusion, Capecitabine 1000mg/m² orally for 14 days, Q3w) combined with Bevacizumab (7.5mg/kg IV infusion, D1, Q3w) + PD-1 inhibitor (Toripalimab 240mg IV infusion, D1, Q3w). Following completion of total neoadjuvant therapy, the treatment strategy (watch-and-wait or surgical resection) will be selected based on tumor response. The decision regarding adjuvant chemotherapy will be determined according to postoperative pathological findings.

Drug: PD-1 inhibitor based immunotherapy

Interventions

PD-1 inhibitor based immunotherapy DRUG

Short-course radiotherapy (25Gy/5Fx) followed by 4 cycles of CAPOX regimen (Oxaliplatin 130mg/m² IV infusion, Capecitabine 1000mg/m² orally for 14 days, Q3w) combined with Bevacizumab (7.5mg/kg IV infusion, D1, Q3w) + PD-1 inhibitor (Toripalimab 240mg IV infusion, D1, Q3w).

Intervention 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:

• Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
• Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
• Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
• Age 18 to 75 years.
• ECOG Performance Status of 0 to 1, without severe comorbid medical conditions.
• Adequate organ function:
• Hematopoietic: Hemoglobin ≥90 g/L, Platelets ≥80 × 10\^9/L, Absolute Neutrophil Count ≥1.5 × 10\^9/L.
• Hepatic: ALT and AST \< 2.5 × ULN. Renal: Serum Creatinine \< 1.5 × ULN.
• Provision of signed and dated written informed consent.

You may not qualify if:

• Patients found to have BRAF mutations or MSI-H status.
• Patients who have previously received chemotherapy, radiotherapy, immunotherapy, targeted therapy, or surgical resection for colorectal cancer prior to enrollment.
• History or presence of another malignancy (except for early-stage basal cell carcinoma or carcinoma in situ of the cervix) within the past 3 years, with the disease not under control.
• Patients who are pregnant (confirmed by serum or urine β-HCG test) or breastfeeding.
• Patients with severe cardiac, hepatic, renal, neurological, or psychiatric diseases.
• Patients with active infections.
• Poor overall health status, with an ECOG performance status ≥2.
• Patients who have undergone organ transplantation requiring immunosuppressive therapy, or those requiring long-term corticosteroid treatment for autoimmune diseases.
• Patients with comorbid conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the completion of the study.
• Known hypersensitivity to any of the study drugs.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Bo Feng

CONTACT

+86 21 64370045; Fengbo2022@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 21, 2025
• First Posted: September 30, 2025
• Study Start: September 5, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)