Hepatic Arterial Infusion Chemotherapy Combined With Sintilimab and Regorafenib as Adjuvant Therapy for Colorectal Liver Metastasis Patients With a High Risk of Recurrent: a Single-arm, Phase II Study

Inclusion Criteria

• •1. Aged over 18 years， men or women who are not pregnant；
• •2. ECOG PS 0/1 evaluated 14 days before enrollment, and expected survival \>12 months after liver resection;
• •3. Liver function: Child-Pugh score Class A or ≤7 Class B；
• •4. Patients with histologically- or clinically-confirmed CRLM（TxNxM1）and CRS\>2；
• •5. Patients had completely resected Primary lesions and liver metastases as well as no evidence of extrahepatic disease；
• •6. No complications such as bleeding, jaundice, infection, abdominal pleural effusion, obstruction and perforation were observed within 7 days (including 7 days) before the screening. The subjects recovered well after surgery, the surgical incision healed well, the stitches were removed, and the drainage tube was removed;
• •7. Preoperative chemoradiotherapy was limited to neoadjuvant or conversion therapy；
• •8. Patients must have the ability to understand and voluntarily sign the informed consent, and must sign an informed consent before starting any specific procedure for the study；
• •9. Patients were considered capable of complying with the study protocol；
• •6. Idiopathic pulmonary fibrosis, institutionalized pneumonia (e.g., bronchiolitis obliterans), drug-induced or idiopathic pneumonia, or evidence of active pneumonia on a chest computed tomography (CT) scan during screening. Radiation pneumonia was present in the allowable area (fibrosis)
• •7. Active TB disease
• •8. Major cardiovascular disease (such as New York Heart Society Class II or worse heart disease, myocardial infarction, or cerebrovascular accident), unstable arrhythmia, or unstable angina in the 3 months prior to enrollment;
• •9. A history of congenital long QT syndrome or a corrected QT interval \>500ms at screening (calculated using Fridericia's method);
• •10. A history of uncorrected electrolyte disturbances such as serum potassium, calcium, or magnesium
• •11. Received major surgery within 4 weeks prior to the enrollment (except for diagnosis) or expected to require major surgery during the study period;
• •12. Malignancies other than CRC that have developed within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, duct carcinoma in situ, or stage I uterine cancer;
• •13. Severe infections, including but not limited to hospitalization due to infection, bacteremia, or severe pneumonia complications, occurred in the 4 weeks prior to the enrollment;
• •14. Therapeutic antibiotics were given orally or intravenously within 2 weeks prior to the enrollment. Subjects who received prophylactic antibiotics (for example, to prevent urinary tract infections or exacerbations of COPD) were eligible;
• •15. Previous allogeneic stem cell or solid organ transplantation;
• •16. Received live attenuated vaccine within 4 weeks prior to the enrollment, or expected to receive such vaccine during sintilimab treatment or within 5 months after the last dose;
• •17. With untreated or incompletely treated esophageal and/or gastric varicose veins associated with bleeding or at high risk of bleeding. Prior to enrollment, subjects must undergo ultrasound, CT, MRI, or liver elasticity tests, assess the size of all varicose veins (small to large), and be treated according to local standard care. Subjects who received the corresponding examination within 6 months prior to the enrollment do not need to be re-examined;
• •18. Co-infection with HBV and HCV. Subjects with a history of HCV infection but negative PCR results for HCV RNA are considered not infected with HCV;
• •19. Symptomatic, untreated, or progressive central nervous system (CNS) metastases. Asymptomatic subjects whose CNS lesions have been treated are eligible as long as they meet all of the following criteria: They must have measurable lesions outside the CNS according to RECIST v1.1; Subjects had no history of intracranial or spinal bleeding; Metastases are limited to the cerebellar or supratentorial regions (i.e., no midbrain, pontine, medullary, or spinal cord metastases); No evidence of progress between completion of CNS oriented therapy and initiation of study therapy; Subjects had not received stereotactic, whole brain radiation, and/or neurosurgical resection within 28 days prior to the enrollment; There was no need for continuous use of glucocorticoids to treat CNS disease. A steady dose of anticonvulsant therapy is permitted. Asymptomatic subjects with newly detected CNS metastases at the time of screening are eligible after radiotherapy or surgery, and no need for repeated screening of brain scan results;
• •20. Refuse follow-up and participating in other clinical trials that may interfere with this study;
• •21. Patients are not suitable for enrollment judged by investigators.