Paclitaxel liver-artery infusion plus standard chemo for first-line colorectal liver metastases

Inclusion Criteria:

* 1\. Age range: 18 - 75 years old (inclusive), gender not limited.
* 2\. For patients with colorectal liver metastases have been histologically or cytologically confirmed and who are assessed by multidisciplinary team (MDT) to be inoperable for radical surgical resection:

  1. Have not received systemic treatment for the metastatic or recurrent disease;
  2. For patients who have received neoadjuvant/adjuvant therapy before, the time interval between the last administration and disease progression must be ≥ 6 months;
  3. Allow patients who have received local treatment and progressed.
* 3\. According to RECIST v1.1, at least one measurable lesion in the hepatic arterial infusion area (long diameter ≥ 1 cm and no previous local treatment).
* 4\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
* 5\. Life expectancy of at least 3 months.
* 6\. Adequate organ function, with laboratory tests meeting the following criteria (no blood transfusion or hematopoietic growth factors within 14 days)
* 7\. Fertile patients (male and female) must agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence) with their partners during the study and for at least 6 months after the last dose of study intervention. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
* 8\. Fully understand the clinical study and voluntarily sign a written informed consent form.

Exclusion Criteria:

* 1\. Patients known to have microsatellite instability high (MSI-H) or mismatch repair deficiency (dMMR), and have been evaluated by the investigators to be eligible for immune checkpoint inhibitor therapy.
* 2\. Patients known to have wild-type RAS and BRAF, and have been evaluated by the investigators to be eligible for anti-epidermal growth factor receptor (EGFR) drug therapy.
* 3\. Unresolved adverse reactions from previous anti-tumor treatments not yet recovered to CTCAE 5.0 grade ≤ 1 (except for alopecia or other toxicities deemed non-risky by the investigators).
* 4\. Central nervous system metastasis with clinical symptoms, or meningeal metastasis, or there are other evidences indicating that the patient's central nervous system metastasis or meningeal metastatic lesions have not been controlled, and the investigators judges that the patient is not suitable for enrollment.
* 5\. Patients with contraindications for transcatheter arterial infusion.
* 6\. Patients with active infections within 2 weeks prior to administration (NCI CTC AE v5.0 ≥ grade 2) (Defined as requiring intravenous administration of antibacterial, antifungal or antiviral drugs for treatment).
* 7\. Patients with grade 2 or above peripheral neuropathy (NCI CTC AE v5.0).
* 8\. Patients with a history of autoimmune diseases, immunodeficiency disorders, including HIV positive test results, or suffering from other acquired or congenital immune deficiencies, or those currently using immunosuppressive agents.
* 9\. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive with HBV DNA ≥ 2×103 IU/mL (can use continuous antiviral treatment); or anti-hepatitis C virus antibody (HCV-Ab) positive with HCV RNA above the measurable limit; or active syphilis.
* 10\. Patients with known contraindications to capecitabine or oxaliplatin, paclitaxel or cationic liposome, or have severe allergic reactions; note: If the subject has contraindications to bevacizumab or has severe allergic reactions to any component of bevacizumab, it will not affect the enrollment but should not use bevacizumab in the study, and the specific reasons need to be recorded.
* 11\. Patients need to receive strong inducers and strong inhibitors of CYP2C8 and CYP3A4 within 2 weeks before the first study treatment or during the treatment.
* 12\. Patients had or have non-infectious pneumonia/interstitial lung disease that requires systemic glucocorticoid treatment.
* 13\. Severe cardiovascular disease history, including but not limited to:

  * Long QT syndrome;
  * High-degree atrioventricular block;
  * Severe arrhythmia that is not well controlled by medication;
  * Chronic heart failure history and NYHA cardiac function classification ≥ 3;
  * Severe valvular regurgitation or stenosis that requires treatment;
  * Acute coronary syndrome or severe myocardial disease within 6 months before screening;
  * Uncontrolled hypertension;
  * Echocardiography suggests LVEF \< 50%;
* 14\. Patients with a previous history of severe neurological or mental disorders (including epilepsy or dementia) lead to compliance issues.
* 15\. Patients with ultrasound-detected limb vascular thrombosis with potentially serious consequences during screening, or who with thromboembolic events within 3 months prior to enrollment.
* 16\. Patients with a history of severe bleeding, or who experienced major bleeding events such as intracranial hemorrhage, gastrointestinal bleeding, or purpura within the last 3 months.
* 17\. Any other reasons deemed by the investigators.