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

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: PD-1 inhibitor based immunotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07198165

TRAINER-2

Details and patient eligibility

About

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.

Enrollment: 104 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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104 participants in 2 patient groups

Control group

No Intervention group

Description:

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 group

Description:

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.

Treatment:

Drug: PD-1 inhibitor based immunotherapy