A Phase II Study to Evaluate the Safety and Efficacy of Sintilimab Combined with Nab-paclitaxel and Gemcitabine for Neoadjuvant and Adjuvant Therapy of Patients with Resectable and Borderline Resectable Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- 2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
研究概览
简要总结
The purpose of this research is to investigate the activity and safety of the combination of gemcitabine plus nab-paclitaxel and sintilimab as neoadjuvant therapy in treating patients with resectable and borderline resectable pancreatic cancer.
The drugs involved in this study are:
- Sintilimab
- Nab-paclitaxel
- Gemcitabine
详细描述
Pancreatic cancer is a highly fatal disease with a 5-year survival rate of less than 5%, and it is becoming an increasingly common cause of cancer mortality. Neoadjuvant therapy, such as gemcitabine plus nab-paclitaxel, can effectively avoid the proliferation of residual tumors and reduce the risk of lymph node metastasis, implantation metastasis during surgery, and early relapse after operation. Most importantly, it can change the immune status by turning the "immune cold" pancreatic cancer into an "immune hot" condition, which will enable the application of immune checkpoint inhibitors. Sintilimab is an immune checkpoint inhibitor against programmed cell death protein 1, which is applicable for treatment of a range of cancers including non-small cell lung cancer, melanoma, esophageal cancer, and liver cancer. It could block the interaction between PD-1 and its ligands and help the anti-tumor effect of T cells to recover. The present study is intended to investigate the activity and safety of the combination of gemcitabine plus nab-paclitaxel and sintilimab as neoadjuvant therapy in treating patients with resectable and borderline resectable pancreatic cancer.
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
- •Signed informed content obtained prior to treatment
- •Age ≥ 18 years and ≤ 75 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Patients must have imaging evaluations to confirm that their pancreatic adenocarcinoma is resectable and borderline resectable. Patients must have histologically confirmed pancreatic adenocarcinoma, too.
- •Therapy-naïve for their pancreatic cancer. Patients should receive no anti-tumor treatment, including systemic chemotherapy, interventional chemotherapy, high-energy focused ultrasound, radiotherapy, immunotherapy, molecular targeted therapy, and anti-tumor Chinese medicine therapy.
- •No serious dysfunction in blood system, heart, lung function, or autoimmune system (refer to the respective diagnostic criteria)
- •White blood cell (WBC) ≥ 3 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelets (PLT) ≥ 100 × 109/L; Hemoglobin (Hgb) ≥ 90 g/L
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
- •Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
- •Able to comply with research visit plans and other protocol requirements.
排除标准
- •The diameter of the resectable tumor is ≤ 2 cm in imaging evaluation
- •Associated with other malignant tumors
- •Patients receiving anti-tumor treatment before neoadjuvant therapy, including systemic chemotherapy, interventional chemotherapy, high-energy focused ultrasound, radiotherapy, immunotherapy, molecular targeted therapy, and anti-tumor Chinese medicine therapy
- •Use of any other investigational agents
- •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or nursing women
- •History of allergic reactions attributed to compounds of similar chemical or biological composition to nab-paclitaxel, gemcitabine, or sintilimab
- •Patients who are using and need to use warfarin for a long period
- •Patients who are unwilling or unable to comply with study procedures
- •Patients who are expected to be out of the observation period for 14 days or more during the treatment
研究组 & 干预措施
sintilimab + nab-paclitaxel + gemcitabine
Experimental: sintilimab + nab-paclitaxel + gemcitabine nab-paclitaxel at 125 mg/m^2 on days 1, and 8; gemcitabine at 1000 mg/m^2 on days 1, and 8; sintilimab at 200mg on day 1;
干预措施: sintilimab (Drug)
sintilimab + nab-paclitaxel + gemcitabine
Experimental: sintilimab + nab-paclitaxel + gemcitabine nab-paclitaxel at 125 mg/m^2 on days 1, and 8; gemcitabine at 1000 mg/m^2 on days 1, and 8; sintilimab at 200mg on day 1;
干预措施: nab-paclitaxel (Drug)
sintilimab + nab-paclitaxel + gemcitabine
Experimental: sintilimab + nab-paclitaxel + gemcitabine nab-paclitaxel at 125 mg/m^2 on days 1, and 8; gemcitabine at 1000 mg/m^2 on days 1, and 8; sintilimab at 200mg on day 1;
干预措施: gemcitabine (Drug)
结局指标
主要结局
2-year overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel
时间窗: From date of enrollment to the date of death for any cause, assessed 2 months during therapy and 3 months thereafter up to 24 months
To evaluate the overall survival of patients with resectable and borderline resectable pancreatic cancer treated with the combination of sintilimab and gemcitabine plus nab-paclitaxel. Outpatient visit, phone interview
次要结局
- Objective response rate and disease control rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel(One month during therapy and 3 months thereafter up to 24 months)
- Resection rate and R0 resection rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection(One month during therapy and 3 months thereafter up to 24 months)
- Overall survival after the application of sintilimab and gemcitabine plus nab-paclitaxel(From date of enrollment until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months)
- Major pathological response rate after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection(One month during therapy and 3 months thereafter up to 24 months)
- Correlation between patients' immunological parameters before and after the application of sintilimab and gemcitabine plus nab-paclitaxel and prognosis of them(One month during therapy and 3 months thereafter up to 24 months)
- Event-free survival after the application of sintilimab and gemcitabine plus nab-paclitaxel(From date of enrollment until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months)
- Node-negative resection rate, the occurrence rate and severity of perioperative complications after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection(One month during therapy and 3 months thereafter up to 24 months)
- Correlation among ctDNA, serum tumor markers, and CT evaluations before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy.(One month during therapy and 3 months thereafter up to 24 months)
- Recurrence-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel and curative resection(One month during therapy and 3 months thereafter up to 24 months)
- Progression-free survival after finishing the course of the treatment of sintilimab and gemcitabine plus nab-paclitaxel, but being determined as unresectable after surgical exploration(One month during therapy and 3 months thereafter up to 24 months)
- Number and severity of toxicities according to NCI CTCAE version 4.0(One week during therapy and 3 months thereafter up to 24 months)
- Whole exome sequencing before and after the application of sintilimab and gemcitabine plus nab-paclitaxel(One month before therapy and one month after therapy)
- Correlation between circulating tumor DNA (ctDNA) and serum tumor marker before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy(One month during therapy and 3 months thereafter up to 24 months)
- Correlation between ctDNA and CT evaluations before and after neoadjuvant therapy, before and after curative resection, during and after adjuvant therapy, and during and after the maintenance treatment of immunotherapy(One month during therapy and 3 months thereafter up to 24 months)