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RECRUITINGPhase 2INTERVENTIONAL

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

Short-Course Radiotherapy Combined With CAPOX and Bevacizumab, With or Without PD-1 Inhibitors, as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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. - You should be able to carry out daily activities with 0 level of ability (ECOG 0) to 1, without severe comorbid medical conditions. - your organs (liver, kidneys, etc.) are working well enough based on blood tests: Hematopoietic: blood count (hemoglobin) at least 90 g/L, platelet count at least 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 willing to sign a consent form. Who Should NOT Join This Trial: - 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

DRUG

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).

Locations (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Shanghai, China