Combining Icaritin with Bevacizumab and FOLFIRI for liver metastases from colorectal cancer

Inclusion Criteria:

* 1). Age ≥ 18 years. 2).Patients with unresectable advanced metastatic colorectal cancer confirmed by clinical diagnostic criteria and/or histopathological or cytological examination. Metastases include, but are not limited to the liver.

  3). Presence of clearly measurable (RECIST 1.1 compliant) liver metastases on imaging assessment (unresectable by MDT assessment).

  4). Patients who have failed prior first-line systemic systemic therapy, including bevacizumab.

  5).ECOG PS score 0-1. 6). Have normal organ function and meet the following criteria on laboratory tests within 7 days prior to initiation of therapy:
  1. Haemoglobin level \> 80 g/L;
  2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;
  3. Platelet count ≥50×10-9/L;
  4. Serum albumin ≥ 30 g/L;
  5. Total bilirubin ≤ 2 × upper limit of normal (ULN);
  6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 5 × ULN;
  7. Alkaline phosphatase (ALP) ≤ 2.5 x ULN;
  8. creatinine ≤ 1.5 x ULN and creatinine clearance ≥ 50 ml/min. 7). Good swallowing function. 8). Coagulation function: international normalised ratio (INR) ≤ 1.5 x ULN or prothrombin time (PT)≤16s.

     9). Life expectancy ˃3 months. 10). Voluntary participation in this study and voluntary signing of informed consent.

     11). Men and women of gestational age must agree to use adequate contraception throughout the study and for 3 months after the end of treatment.

     Exclusion Criteria:
* 1). Pre-existing or coexisting other active malignant tumours (except for malignant tumours that have been curatively treated and have been free of malignancy that has received curative treatment and has been free of morbidity for more than 5 years or carcinoma in situ that can be cured by adequate treatment).

  2). Concomitant administration of modern Chinese medicinal preparations for antitumour and anti-tumour indications.

  3). Patients who have received chemotherapy or anti-vascular endothelial growth factor receptor (VEGF) therapy.

  4). Patients receiving systemic chemotherapy, hormonal therapy, immunotherapy, approved proteins/antibodies or any experimental drugs or treatments (30 days) or radiotherapy (within 14 days).

  5). Tumour invasion of large blood vessels. 6). Significant cardiovascular compromise within 12 months prior to the first dose of study drug: e.g., New York Heart Association (NYHA) Class II or higher. Stroke, myocardial infarction or cerebral haemorrhage, or arrhythmia associated with haemodynamic instability; Corrected QT (QTc) interval prolongation \>480ms.

  7). Any surgical procedure within the last 28 days. 8). Bleeding from ruptured oesophageal or gastric varices within the last 2 weeks, or unconfirmed severe varices and bleeding in the judgement of the investigator.

  9). Bleeding or thrombotic disorders or on thrombolytic therapy, coagulation disorders; study intervention Clinically significant haemoptysis or tumour bleeding of any cause within 2 weeks prior to first dose.

  10). Patients with uncontrolled epilepsy, history of central nervous system disease or psychiatric disorders, hypertension.

  11). Active autoimmune disease requiring systemic therapy within the past 2 years.

  12). Clinically significant ascites on physical examination that cannot be controlled medically.

  13). Pregnant or breastfeeding female patients, or those unwilling to use contraception during the trial.

  14). Known hypersensitivity to Icaritin, Bevacizumab and chemotherapeutic drug components.

  15). Suspect that it may cause contraindication to the use of the drug, or affect the reliability of the study results, or place the patient at a disease or condition that places the patient at high risk for treatment complications, or affects the patient's adherence to the trial medication.

  16). Vulnerable populations, including those with mental illness, cognitive impairment, critically ill patients, illiteracy, etc.

  17). Presence of other reasons that the investigator considers inappropriate for participation in this study.