Neoadjuvant Safety of Sintilimab + XELOX + Bevacizumab in pMMR/MSS CRLM Patients

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Colorectal liver metastasis, pMMR/MSS, Sintilimab, XELOX, Bevacizumab Read More

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