GOT Applied As Neoadjuvant Regimen for Patients of Resectable ICC with High-risk Factors of Recurrence

Prior treatment

• Anti-cancer therapy or surgery such as radiotherapy, radiofrequency ablation, interventions in 28 days prior to the first dose of the study (except for previous non-tumor-related surgeries and diagnostic biopsies)；
• Long-term glucocorticoid users require long-term systemic hormones (equivalent to \>10 mg Prednisone/day) or any other form of immunosuppressive therapy；
• Clinically significant bleeding or bleeding tendencies within 3 months prior to enrollment or on thrombolytic or anticoagulant therapy；
• Active severe clinical infections (\> grade 2, NCI-CTCAE version 5.0), including active TB; Have a history of active TB infection at least 1 year before enrolment, have not received regular anti-tuberculosis (TB) treatment or are still active; active, known or suspected autoimmune disease;
• Patient who are receiving renal replacement therapy；
• Others situations are not expected to tolerate surgical treatment；

Other illness

• hepatitis B virus (HBV) DNA\>2000 copies/ml, hepatitis C virus (HCV) RNA\>1000;
• Clinically significant cardiovascular diseases; With hypertension, antihypertensive drugs cannot be well controlled (systolic blood pressure≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
• History of other malignancies in the last 5 years. With the exception of carcinoma of the skin basal cells that have been cured or carcinoma in situ in the cervix;
• People with allergic reactions to any component of the drug under study;
• There are other unsuitable candidates for clinical trials, such as alcohol dependence, mental illness, pregnancy (or lactation).

Lab values

• Uncontrolled diabetes mellitus (fasting blood glucose ≥10 mmol/L), severe lung disease (eg, acute lung disease, pulmonary fibrosis that affects lung function, interstitial lung disease). except for recovered radiation pneumonia);

Other

• Patient with non-intrahepatic cholangiocarcinoma；
• Distant metastasis；
• Patients with complete bowel obstruction and incomplete intestinal obstruction that require treatment, but patients who have been relieved of obstruction by ostomy or stent placement can be enrolled；

• 18-75 yo;
• Patients of Pathological confirmed intrahepatic cholangiocarcinoma who has never received systemic therapy including chemotherapy, immunotherapy, target therapy and other anti-cancer therapy;
• Patients of resectable ICC with high risk recurrent factors:
  • ①Maximum diameter greater than 5cm or multiple tumors.
  • ②Preoperative CA19-9 greater than 200 Unit(U)/mL
  • ③Tumors invaded adjacent blood vessels
  • ④Preoperative radiology hints suspected regional lymph node metastasis.
  • ⑤Tumor tissues confirmed by CT or MRI, at least one measurable lesion exists according to RECIST v1.1.
• Eastern Cooperative Oncology Group(ECOG)-Performance status(PS) score is 0 before first drug administration;
• Child-Pugh classification is class A;
• Estimated overall survival is greater than 16 weeks;
• The level of organ function meets the criteria and can tolerate surgery before the first treatment. Main organs meet the criteria as below:
  • haemoglobin≥90g/L，Neutrophil count≥1.5×10⁹/L，Platelet count≥100×10⁹/L；Aspartate or alanine aminotransferase≤5 upper limits of normal(ULN），alkaline phosphatase≤2.5 ULN，Serum albumin≥30g/L；serum creatinine\<1.5 ULN；International normalized ratios（INR）≤2 or Prothrombin time（PT）exceed ULN≤6s；Creatinine clearance≥60 mL/min.
• Male and female subjects with potential fertility had to agree to the use of effective contraceptive methods throughout the study period；
• Sign an informed consent form agreeing to provide previously preserved specimens of tumor tissue or fresh detection of tumor lesions.