Chemoradiotherapy, Immunotherapy, Rectal Adenocarcinoma, Rectal Cancer, Rectal Cancer Patients, Rectal Cancer, Radiotherapy, Targeted Therapy, Total Neoadjuvant Therapy, Total Neoadjuvant Treatment
Conditions
Keywords
Rectal cancer, Total Neoadjuvant Therapy, Immunotherapy, Targeted therapy, Chemoradiotherapy
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.
Interventions
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).
Sponsors
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response rate | 2 weeks after the surgery | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Metastasis Rate | from enrollment to the end of follow-up at 48 months | 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. |
| Local Recurrence Rate | from enrollment to the end of follow-up at 48 months | 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. |
| Overall Survival (OS) | from enrollment to the end of follow-up at 48 months | 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. |
| Disease-Free Survival (DFS) | from enrollment to the end of follow-up at 48 months | 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. |
| Tumor Regression Grade(TRG) | 2 weeks after the surgery | Measurement Method: Chi-square test or Fisher's exact test |
| Sphincter Preservation Rate | 2 weeks after the surgery | 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. |
| Pathological Stage | 2 weeks after the surgery | ypT and ypN staging Measurement Method: Chi-square test or Fisher's exact test |
Countries
China
Contacts
Primary ContactBo Feng
Outcome results
None listed