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

Phase 2RecruitingNCT07198165

Ruijin Hospital104 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

104

Conditions

Rectal Cancer Rectal Adenocarcinoma Rectal Cancer, Radiotherapy Rectal Cancer Patients

Interventions

PD-1 inhibitor based immunotherapyDRUG

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).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 2 weeks after the surgery

Secondary Outcomes

Disease-Free Survival (DFS)

Measurement Method: Kaplan-Meier survival analysis, Log-rank test to compare survival curves between the two groups. Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.

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

Distant Metastasis Rate

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

Local Recurrence Rate

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

Overall Survival (OS)

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

Pathological Stage

ypT and ypN staging Measurement Method: Chi-square test or Fisher's exact test

Time frame: 2 weeks after the surgery

Tumor Regression Grade(TRG)

Measurement Method: Chi-square test or Fisher's exact test

Time frame: 2 weeks after the surgery

Sphincter Preservation Rate

Measurement Method: Logistic regression analysis Methods for Handling Missing Values: * For missing data, the Last Observation Carried Forward (LOCF) method or multiple imputation method will be applied. * For subjects with significant non-compliance or loss to follow-up, sensitivity analysis will be considered to assess the impact on results.

Time frame: 2 weeks after the surgery

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts