Fecal Microbiota Transplantation Combined With SHR-1701(an Anti-PD-L1/TGF-βRII Fusion Protein) and Nab-Paclitaxel Plus Gemcitabine as First-Line Treatment for Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma：A Randomized, Open-Label, Single-Center, Two-Arm, Prospective Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Median Progression-Free Survival (mPFS)
研究概览
简要总结
This is a prospective, single-center, randomized, open-label, two-arm Phase II clinical trial design to evaluate the feasibility, safety and preliminary efficacy of combining fecal microbiota transplantation （FMT） with Nab-paclitaxel plus Gemcitabine and as first-line treatment in patients for locally advanced or metastatic pancreatic ductal adenocarcinoma （PDAC）.
详细描述
This phase II study aims to assess the efficacy and safety of fecal microbiota transplantation （FMT) combined with SHR-1701 and Nab-paclitaxel plus Gemcitabine as first-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma （PDAC) . This study plans to enroll a total of 60 treatment-naïve patients diagnosed with locally advanced or metastatic PDAC; eligible patients will be randomized in a 1:1 ratio into experimental group (group A, n=30）or control group (group B, n=30) The primary objective is to evaluate the median progression free-survival （mPFS） of fecal microbiota transplantation （FMT） combined with SHR-1701 Plus AG chemotherapy in patients for locally advanced or metastatic pancreatic ductal adenocarcinoma （PDAC）.
The secondary objectives are to determine the overall survival （OS）, objective response rate （ORR）, disease control rate （DCR）, and duration of response （DoR） according to RECIST v1.1 criteria. Furthermore, to assess adverse drug events （ADEs） and other reported adverse events will be evaluated and graded in based on the NCI-CTCAE, version 6.0.
As exploratory objectives, this study aims to investigate multi-omics prognosis prediction biomarkers and their associated mechanisms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Main inclusion criteria 1）18-75 years 2）Histologically or cytologically confirmed pancreatic ductal adenocarcinoma that is locally advanced, unresectable with no prior systemic therapy for advanced disease.
- •3）At least one measurable lesion per RECIST v1.
- •4）Adequate hematologic, hepatic, renal, cardiac and coagulation function. 5）Have the ability to ingest capsule. 6）ECOG performance status of 0-1 7）Life expectancy of at least 3 months
排除标准
- •Patients with metastatic disease, peritoneal metastasis, malignant ascites, or unsuitable for NALIRIFOX treatment.
- •Patients with active autoimmune diseases or requiring systemic immunosuppressive therapy and patients with immunodeficiency, HIV infection, or history of organ/hematopoietic stem cell transplantation.
- •Patients with uncontrolled infection, active hepatitis B/C infection, or severe infectious diseases.
- •Patients with gastrointestinal perforation, fistula, abscess, active bleeding, or contraindications to FMT.
- •Patients with severe cardiac, hepatic, renal, or pulmonary dysfunction.
- •Patients with known hypersensitivity to study drugs or FMT-related components.
研究组 & 干预措施
FMT+Chemotherapy+Immunotherapy
Bowel preparation with Polyethylene Glycol is administered on Day 0, followed by Fecal Microbiota Transplantation （FMT） on Day 1. AG is administered intravenously at Day8，Day15 and Day 22 of each 28 days. SHR-1701 is also initiated on Day 8 and administered intravenously once every 3 weeks, with FMT given concurrently with each SHR-1701.If the patient's disease is assessed as not having progressed, the current treatment regimen will be continued. For patients with stable or partial or complete response, the current treatment regimen will be continued in accordance with the study protocol.
干预措施: FMT+Chemotherapy+Immunotherapy (Drug)
Chemotherapy+Immunotherapy
AG is administered intravenously at Day8，Day15 and Day 22 of each 28 days. SHR-1701 is also started on Day 8 and administered intravenously once every 3 weeks, for patients with stable or partial or complete response, the current treatment regimen will be continued in accordance with the study protocol.
干预措施: Chemotherapy+Immunotherapy (Drug)
结局指标
主要结局
Median Progression-Free Survival (mPFS)
时间窗: From the first dose of study treatment until the first documented radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first, assessed up to 12 months.
The primary efficacy outcome will be median progression-free survival （mPFS）, defined as the time from the date of first administration of study treatment to the first occurrence of objectively documented disease progression or death from any cause, whichever occurs first. mPFS will be used to evaluate the potential antitumor activity of FMT combined with SHR-1701 and nab-paclitaxel Plus Gemcitabine in the treatment-naïve patients with locally advanced pancreatic ductal adenocarcinoma （PDAC）. Tumor response and disease progression will be assessed by the investigator according to Response Evaluation Criteria in Solid Tumors （RECIST）, version 1.1. Radiographic assessments will be performed at baseline and subsequently every 9 weeks （±1 week） during the treatment period.
次要结局
- Objective Response Rate （ORR）(From the first dose of study treatment until documented disease progression or initiation of a new anticancer therapy, assessed up to 12 months.)
- Disease Control Rate （DCR）(From the first dose of study treatment until documented disease progression or initiation of a new anticancer therapy, assessed up to 12 months.)
- Duration of Response (DoR)(From the first documented complete or partial response until the first documented disease progression or death from any cause, whichever occurs first, assessed up to 12 months.)
- Overall Survival (OS)(From the first dose of study treatment until death from any cause, assessed up to 36 months.)
- Safety and Adverse Events(approximately 3 years)