A Pilot Study of PD-1 Inhibitor in Combination With Gemcitabine/Cisplatin for Patients With Advanced Unresectable or Metastatic Biliary Tract Cancers
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- The percentage of patients alive and without progression at 6 months
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
研究组 & 干预措施
PD-1 inhibitor + Gemcitabine+Cisplatin
Patients will be enrolled in the experimental arm and will receive Gemcitabine on day 1 and 5 (1000mg/m2 ) +Cisplatin on day 1(75mg/m2)+ PD-1 inhibitor on day 3 (Nivolumab 3mg/kg, or SHR-1210 200mg) every 3 weeks. If there is continued benefit after 6 months, PD-1 inhibitor will be administered as maintenance treatment until tumor progression or death.
干预措施: PD-1 inhibitor + Gemcitabine + Cisplatin (Drug)
结局指标
主要结局
The percentage of patients alive and without progression at 6 months
时间窗: 6 months
The primary objective of this trial is the progression free survival (PFS) at 6 months in patients with advanced unresectable or metastatic BTCs treated with PD-1 inhibitor in combination with gemcitabine plus cisplatin. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition
次要结局
- The percentage of patients that respond to combination treatment(Enrolled patients will be followed until death, withdrawal from study, or until 2 years.)
- Median overall survival time(Patients will be followed until death, withdrawal from study, or until 2 years.)
- List of adverse event frequency and grade(Up to 120 days after last administration of PD-1 inhibitor)
研究者
Han weidong
Ph.D
Chinese PLA General Hospital