Explore the Efficacy and Safety of Sintilimab Plus Bevacizumab Combined With Gemcitabine and Albumin-paclitaxel (AG Regimen) in First-line Treatment of Initial Unresectable Gallbladder Cancer: a Phase II Clinical Study
Study design: Prospective, single-arm, single-center phase II clinical study; Primary endpoint: Objective response rate via investigator, Safety; Secondary endpoints: disease control rate, disease-free survival, overall survival, and proportion of acceptable radical resection of primary lesions; Main characteristics of enrolled patients: Patients with initially unresectable gallbladder cancer; Interventions: Combination of Gemcitabine, Nab-paclitaxel, Sintilimab and Bevacizumab; Sample size: Using Simon's two-stage design, 15 patients in the first stage, and if more than 4pts response, enlarge the sample size to 45 patients in total; Treatment until: 1. successfully conversed to resectable disease 2. progressed disease 3. intolerable toxicity 4. patient requests withdrawal; Research process: In this study, patients who met the inclusion criteria were evaluated at the end of every 9 weeks of treatment, up to surgical treatment or disease progression; Safety evaluation: Evaluate adverse reactions according to CTCAE 5.0; Follow up: every 90 days (±7 days) until the subject died, lost follow-up or the end of the study.
⁃ 1\. Before the implementation of any trial-related procedures, sign a written informed consent 2. Male or female ≥18 years old, ≤75 years old 3. Gallbladder carcinoma confirmed by histology or cytology 4. No previous systemic anti-tumor therapy (radiotherapy, chemotherapy, targeted or immunotherapy, etc.) 5. Expected survival time \> 3 months 6. At least 1 measurable lesion according to RECIST1.1 criteria 7. ECOG PS score of 0-1 8. Sufficient organ function, the subject needs to meet the following laboratory indicators:
• Absolute value of neutrophils (ANC) ≥ 1.5x109/L and platelets ≥ 90×109/L without using granulocyte colony-stimulating factor in the past 14 days;
• Hemoglobin \> 9g/dL without blood transfusion or use of erythropoietin in the past 21 days;
• Total bilirubin ≤ 3 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are ≤2.5×ULN (patients with liver metastases are allowed ALT or AST ≤5×ULN);
• Alkaline phosphatase (AKP) ≤2.5×ULN
• Creatinine clearance rate (calculated using the Cockcroft-Gault formula) ≥ 50 ml/min;
• Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
• Normal thyroid function, defined as thyroid-stimulating hormone (TSH ≤ 10) within the normal range; thyroid dysfunction without clinical significance after thyroid hormone supplementation can also be included.
• Myocardial enzyme spectrum is within the normal range (such as simple laboratory abnormalities that are judged by the investigator to have no clinical significance are also allowed to enter the group); 9. For female subjects of childbearing age, they should receive a urine or serum pregnancy test within 3 days before receiving the first study drug administration (day 1 of cycle 1) and the result is negative. If the urine pregnancy test result cannot be confirmed negative, a blood pregnancy test will be ordered. Women of non-reproductive age are defined as postmenopausal for at least 1 year, or who have undergone surgical sterilization or hysterectomy 10. If there is a risk of pregnancy, all subjects (regardless of male or female) need to use contraceptive measures with an annual failure rate of less than 1% during the entire treatment period until 120 days after the last study drug administration