study of pd-1 inhibitor in combination with gemcitabine/cisplatin for advancer btcs

Conditions: Biliary Tract Cancer

Summary: this is a single-arm, phase i/ii trial in biliary tract cancer (btc) patients. the purpose of this trial is to evaluate the safety and effect of pd-1 inhibitor in combination with gemcitabine/cisplatin chemotherapy in patients with advanced unresectable or metastatic btcs. the primary objective: 6-month progression free survival (pfs). the second objectives: objective clinical response(according to recist version 1.1), safety, symptom control and quality of life (qol) (according to eortc qol c30 and bil 21), overall survival. the exploratory objectives: assessment of immunological response (cytokines, lymphocyte phenotype, immunoglobulins), and evaluation of pathological, immunological and clinical predictive factors for response/toxicity.


Eligibility criteria:
inclusion criteria: * age≥18 years with estimated life expectancy \>3 months. * histopathological/cytological diagnosis of unresectable or recurrent / metastatic biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder) and had at least one measurable disease (≥1cm) by ct or mri. * patients should provide samples of tumor tissue biopsied or resected no more than 3 months before enrollment and be willing to accept biopsy in the process of the study. * patients may have received prior radiotherapy,chemotherapy,or other local ablative therapies, which completed ≥ 4 weeks prior to registration and patient has recovered to \<= grade 1 toxicity. * ecog (eastern cooperative oncology group) performance status of 0-2. * adequate organ and marrow function obtained ≤ 2 weeks prior to registration as defined below: leukocytes greater than or equal to 3.0 x 10\^9/l absolute neutrophil count greater than or equal to 1.0 x 10\^9/l platelets greater than or equal to 100 x 10\^9/l hemoglobin greater than or equal to 90 g/l total bilirubin less than or equal to 2 xuln serum albumin should be no less than 25g/l alt or ast less than 2 xuln serum creatinine less than 1.5 x uln * ability to understand and willingness to sign a written informed consent document. * women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 120 days after the last dose of the drug. exclusion criteria: * active, known or suspected autoimmune diseases. * known brain metastases or active central nervous system (cns). if patients with cns metastases were treated with radiotherapy for at least 3 months prior to enrollment and have no central nervous symptoms and are off corticosteroids, they will be eligible but will need a brain mri prior to enrollment. * participants are being treated with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. * prior therapy with anti-pd-1, anti-pd-l1, or anti-ctla-4 antibody (including ipilimumab or any other antibody specifically targeting t-cell costimulation or checkpoint pathways). * history of severe hypersensitive reactions to other monoclonal antibodies. * history of allergy or intolerance to study drug components. * substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results. * history or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function. * uncontrolled intercurrent illness including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient. * history of human immunodeficiency virus (hiv) infection or acquired immunodeficiency syndrome (aids). * pregnant or breast-feeding patients. women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented. * previous or concurrent cancer within 3 years prior to treatment start except for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors \[ta (non-invasive tumor), tis (carcinoma in situ) and t1 (tumor invades lamina propria)\]. * vaccination within 30 days of study enrollment. * active bleeding or known hemorrhagic tendency. * patients with unhealed surgical wounds for more than 30 days. * being participating any other trials or withdraw within 4 weeks.