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

• Status: Recruiting
• Trial end date: 2023-06-30
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Treatments: Bevacizumab; Capecitabine; Oxaliplatin

Criteria

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