Prospective Safety Study of Sintilimab Combined With XELOX Plus Bevacizumab for Preoperative Neoadjuvant Therapy of CRLM Patients With pMMR/MSS Status

neoSXB-MSS-CRLM

This prospective, single arm study aims to evaluate the preoperative neoadjuvant safety of Sintilimab combined with XELOX plus bevacizumab in colorectal patients with liver metastasis and pMMR/MSS status.

2021-06-16

2023-10-30

2024-10-30

Active (not recruiting)

Early phase I

36

Inclusion Criteria: * Age ≥18 years old and ≤75 years old * Histologically confirmed colorectal adenocarcinoma * Radiologically and/or pathologically confirmed liver metastasis * Immunohistochemistry and/or genetic testing confirmed pMMR/MSS * Absence of extrahepatic metastasis confirmed by CT, MRI or PET/CT (if necessary) * Primary lesion has been or can be removed by radical surgery * Liver metastases can be resected (or using intraoperative radiofrequency) and is expected to achieve tumor-free status (NED) after surgery. Resectable liver metastases are defined explicitly as ① less than 5 metastatic lesions; ② R0 resection is achievable by resection or intraoperative radiofrequency; ③ Remaining liver volume is expected to be sufficient after surgery; ④ The following can be retained after resection: One hepatic vein, preserve blood flow in and out of the remaining liver, the bile duct, and at least 2 adjacent livers segments ⑤ There is no extrahepatic metastasis. * Apart from surgical resection of the primary lesion, he/she has not received any anti-tumor treatment for liver metastasis (including chemotherapy, targeted drugs, interventional therapy, immunotherapy, radiotherapy, etc.) * Normal hematological function (platelets\>90×109/L; white blood cells\>3×109/L; neutrophils\>1.5×109/L) * Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN), transaminase ≤ 5 times ULN, alkaline phosphatase ≤2.5 ULN, No ascites, normal coagulation function, albumin ≥35g/L * Child-Pugh classification of the liver is A * Serum creatinine is less than the upper limit of normal (ULN), or the calculated creatinine clearance rate is greater than 50ml/min (using Cockcroft-Gault formula) * ECOG score 0-1 * Life expectancy\> 3 months * Signed and written informed consent * Willing and able to follow up until death or the end of the study or the study is terminated Exclusion Criteria: * Presence of distant metastases outside the liver after the diagnosis of colorectal cancer * Liver metastases have been treated with chemotherapy, targeted drugs, intervention, immunotherapy, radiotherapy, etc. * No surgical resection plan for liver metastases * Received oxaliplatin-containing adjuvant chemotherapy in the past 1 year * Any residual toxicity from previous chemotherapy (except for hair loss), such as peripheral neuropathy ≥NCI CTC v3.0 Grade 2 * Use of immunosuppressive drugs within 1 week before treatment, not including nasal sprays, inhalation or other local treatments, partial glucocorticoids or physiological doses of systemic glucocorticoids (i.e. not more than 10 mg/day prednisone or equivalent doses of other glucocorticoids) or use of corticoids to prevent contrast agent allergy * Suffering from interstitial lung disease that requires steroid therapy * Medical history of active autoimmune disease that needs symptomatic treatment within the past 2 years. Vitiligo, psoriasis, hair loss, or Grave's disease that do not require systemic treatment within the past 2 years, or hypothyroidism patients that only need thyroid hormone replacement therapy and type I diabetic patients requiring only insulin replacement therapy can be enrolled * History of primary immunodeficiency * Active tuberculosis * Known history of allergies related to organ transplantation or hematopoietic stem cell transplantation * Allergic to any monoclonal antibody or chemotherapeutic drug (fluorouracil, oxaliplatin) and its ingredients * Have bleeding tendency or coagulopathy * Patients with apparent symptoms of intestinal obstruction * Hypertensive crisis or hypertensive encephalopathy * Serious uncontrollable systemic complications such as infection or diabetes * Clinically severe cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (enrollment within the first 6 months), uncontrollable hypertension, unstable angina pectoris, heart failure (NYHA 2-4), arrhythmia requiring medical treatment * Presence of central nervous system disease ( such as primary brain tumor, history of uncontrollable epilepsy, any brain metastases or stroke) * Suffered from other malignant tumors in the past 5 years (except resected skin basal cell carcinoma and/or cervical carcinoma in situ) * Received any drug treatment used for this study in the last 28 days * Women who are pregnant and breastfeeding. Women of childbearing age who do not use or refuse to use effective non-hormonal contraceptive methods (intrauterine contraceptive ring, barrier contraception combined with spermicidal gel or female sterilization ) (\<2 years after the last menstruation) or men with childbearing potential who are unable or unwilling to comply with the research protocol

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2024-01-09