A Phase I/II, Open-label, Single-center Study to Evaluate the Safety and Efficacy of the Pan-immunotherapy in Subjects With Local Advanced/Metastatic Biliary Tract Cancer
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS) at 6 months
研究概览
简要总结
Biliary tract cancer (BTC) is a rare heterogeneous collection of malignancies arising within the biliary tract, characterized by innate chemoresistance and abysmal prognosis. PD-1 blockade has been developed to a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This open-label, phase I/II study is designed to assess the safety and efficacy of Manganese primed combined therapy of anti-PD-1 antibody and gemcitabine/cisplatin chemotherapy.
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
- •≥ 18 years old.
- •Life expectancy of at least 3 months.
- •Subjects must have Histopathological/cytological diagnosis of unresectable or recurrent /metastatic biliary tract carcinoma (intra-hepatic, extrahepatic or gall bladder).
- •Eastern Cooperative Oncology Group performance status 0-
- •Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
- •Subjects 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.
- •Subjects with Anti-PD-1 antibody treatment history are eligible which must be resistance.
- •Adequate organ function.
- •Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
排除标准
- •Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
- •Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
- •Prior organ allograft.
- •Women who are pregnant or breastfeeding.
- •Women with a positive pregnancy test on enrollment or prior to investigational product administration.
- •Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
研究组 & 干预措施
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
干预措施: Manganese Chloride (Drug)
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
干预措施: nab-paclitaxel (Drug)
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
干预措施: Gemcitabine (Drug)
Manganese primed anti-PD-1 antibody plus nPG chemotherapy
Subject received Manganese primed anti-PD-1 antibody, nab-paclitaxel and gemcitabine every 3 weeks until achieving a second assessable stable disease or up to a maximum of 12 cycles. Treatment continued until progressive disease, development of unacceptable toxicity, or withdrawal of consent.
干预措施: anti-PD-1 antibody (Drug)
结局指标
主要结局
Progression-free survival (PFS) at 6 months
时间窗: 6 months
Progression free survival (PFS) at 6 months in patients with local advanced /metastatic BTCs treated with the combined regimen. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (RECIST V1.1) definition
Number of Subjects with treatment-related adverse events (AEs)
时间窗: 12 months
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.
次要结局
- Disease control rate (DCR)(12 months)
- Overall survival (OS)(24 months)
- Object response rate (ORR)(12 months)
- Number of participants with laboratory test abnormalities(12 months)
研究者
Han weidong
Principal Investigator
Chinese PLA General Hospital