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

NCT ID: NCT07198165

Last Updated: 2025-09-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-05
• Study Completion Date: 2030-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control group

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention group

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.

Group Type: EXPERIMENTAL

PD-1 inhibitor based immunotherapy

Intervention Type: 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).

Interventions

PD-1 inhibitor based immunotherapy

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 Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
• Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bo Feng

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Bo Feng

Role: CONTACT

Fengbo2022@163.com

+86 21 64370045 ext. +86 1351210399

Facility Contacts

Bo Feng

Role: primary

Fengbo2022@163.com

+86 21 64370045

Other Identifiers

TRAINER-2

Identifier Type: -

Identifier Source: org_study_id