Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) accounts for 0.4%-14.2% of primary hepatocellular carcinoma. As imaging and pathological diagnostic techniques for liver tumors have improved, the detection rate of cHCC-CCA puncture biopsies and surgical procedures has increased. Oxaliplatin-containing chemotherapy was previously recommended for the treatment of advanced cHCC-ICC, but its efficacy was not satisfactory. Targeted therapy and immunotherapy have made breakthroughs in both advanced HCC and CCA, providing a new direction for exploration in the treatment of advanced cHCC-CCA. Currently, targeted combination immunotherapy has become the preferred first-line treatment strategy for advanced HCC. Chemotherapy combined with immunotherapy is also the preferred first-line treatment option for advanced CCA. To balance the treatment of HCC and ICC, this study further investigates the efficacy and safety of Gemox chemotherapy combined with anlotinib and Sintilimab(anti-PD-1 monoclonal antibody) immunotherapy in advanced cHCC-ICC, to provide a new treatment strategy and reference for the clinical treatment of advanced cHCC-CCA patients.

Inclusion criteria

• .Age 18-75 years;
• .Histologically or cytologically confirmed diagnosis of aCombined hepatocellular-cholangiocarcinoma;
• .Non resectable or metastatic cHCC-ICC patients who have not received systemic treatment or first-line treatment progress (only non arotinib Targeted therapy or non GEMOX chemotherapy) in the past, and have at least one measurable lesion (RECIST v1.1);
• .Life expectancy ≥ 3 months;
• .ECOG PS 0-1;
• .Child Pugh A/B ≤ 7;
• .Adequate organ function including the following:Total bilirubin ≤1.5 times upper limit of normal (ULN),Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN,Alkaline phosphatase≤2.5×ULN (If the tumor invaded the liver, ≤3×ULN), Serum creatinine≤1.5×ULN,Serum amylase and lipase≤1.5×ULN,International standardized ratio (INR)/partial prothrombin time (PTT)≤1.5×ULN;Platelet count ≥ 75,000 /mm3.Hemoglobin (Hb) ≥ 9 g/dL.Absolute neutrophil count (ANC) ≥ 1500/mm3.
• .Strict contraception.
• .Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion criteria

• Has a history of severe allergic reactions to chimeric, human or humanized antibodies, or fusion proteins.
• Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures;
• History of other malignant tumors in the past 5 years, except for malignant tumors that have received treatment for the purpose of cure, and have no known active diseases for ≥ 5 years before the first administration, and have a low potential risk of recurrence; Fully treated non Melanoma skin cancer or malignant lentigo without disease evidence; Fully treated Carcinoma in situ, no disease evidence;
• Moderate or higher amounts of pleural and ascitic fluid with clinical symptoms;
• Active bleeding or abnormal coagulation function (PT>16s, APTT>43s, INR>1.5) × ULN), with a tendency to bleed or undergoing thrombolysis, anticoagulation, or antiplatelet therapy;
• Hepatic encephalopathy;
• Within the past 6 months, there has been a history of gastrointestinal bleeding or a clear tendency for gastrointestinal bleeding, such as known local active ulcer lesions, fecal occult blood+or above, which cannot be included in the group; If there is continuous fecal occult blood, gastroscopy should be performed;
• Patients with severe gastroesophageal varices who require interventional treatment;
• Untreated active hepatitis B. (Note: Hepatitis B patients who receive antiviral treatment and whose HBV Viral load is less than 2000IU/ml can be allowed to participate in the study)
• Active hepatitis C, that is, those who are anti-HCV positive or HCV-RNA positive and have abnormal liver function;
• Having a history of psychotropic substance abuse, unable to quit, or having a history of mental disorders;
• Patients who received solid organ transplantation or bone marrow transplantation, or had active autoimmune diseases requiring systemic Sex therapy within 2 years before the first administration;
• Existence of immune deficiency diseases or HIV infection;
• There has been objective evidence that Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and serious impairment of lung function exist in the past or at present;
• Major surgery on the liver or other parts has been performed within 4 weeks before the first administration, or minor surgery (such as simple resection, tooth extraction, etc.) has been performed within 1 week before the first administration;
• Received the vaccine within 30 days before the first administration;
• Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 4 weeks prior to the first administration;
• For any significant clinical and laboratory abnormalities, the researchers believe that they will affect the safety evaluators, such as: active infection requiring systemic Sex therapy, uncontrollable diabetes, hypertension patients who cannot fall to the normal range (systolic pressure>140mmHg, diastolic pressure>90mmHg), myocardial infarction within 6 months, thyroid dysfunction (>NCI CTCAE v4.0 Level 1 standard) after treatment with two or less antihypertensive drugs;
• Researchers believe that it is not suitable for inclusion in the study.