Bortezomib Combined with PD-1 MAb and MFOLFIRINOX for First-line Treatment of Metastatic Pancreatic Cancer：An Exploratory Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
This is an single-center, prospective, open-label clinical trial, to explore the safty and efficacy of combination of Bortezomib, Sindilizumab, and mFOLFIRINOX Chemotherapy (oxaliplatin, fluorouracil, irinotecan, leucovorin) in metastatic pancreatic cancer
详细描述
Phase 1 (Evaluation of Drug Tolerance) Primary objective: To evaluate the tolerability of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer, and to determine the dose of bortezomib in the combination regimen; Secondary objectives: To evaluate the immunogenicity characteristics and safety of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Phase 2 (Dose Expansion) Primary objective: To evaluate the tolerability and efficacy of the combination regimen of bortezomib, PD-1 mAb and mFOLFIRINOX in patients with advanced metastatic pancreatic cancer; Secondary Objective: ORR; PFS; OS; and to evaluate the immunogenicity and safety of bortezomib, PD-1 mAb and mFOLFIRINOX in subjects with advanced metastatic pancreatic cancer; and to explore biomarkers related to combination therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma (PDAC).
- •Recurrent disease or metastatic disease (such as liver, peritoneum, lung) evaluated by abdominal contrast-enhanced CT, MRI, and chest CT. PET/CT or other imaging examinations would be used if necessary.
- •Never receive any systematic treatment or Progression after fisrt line Gemcitabine base chemotherapy
- •ECOG score 0 or
- •Serum creatinine level is normal, and serum total bilirubin level is less than 1.5 x ULN.
- •ALT and AST are less than 2 x ULN.
- •Signed informed consent.
排除标准
- •History of participation of other clinical trails within 4 weeks
- •History of autoimmune disease or other condition receiving glucocorticoid treatment
- •History of receiving chemotherapy within 2 weeks
- •History of radiotherapy and molecular target therapy within 2 weeks
- •History if active tuberculosis
- •History of malignance treatment in the past, excluding basal and cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma
- •Major cardiovascular diseases (including myocardial infarction, unstable angina, congestive heart failure, severe uncontrolled arrhythmia) during the past six months of enrollment.
- •Hematological precancerous diseases, such as myelodysplastic syndromes.
- •Evidence of clinical-related or previous interstitial lung disease, such as noninfectious pneumonia or pulmonary fibrosis, or baseline chest CT scan or chest X-ray findings
- •Previous or physical findings of central nervous system disease, except for adequately treated (e.g. primary brain tumors, uncontrolled seizures or strokes with standard medications)
- •Preexisting neuropathy > 1 (NCI CTCAE).
- •Immune deficiency syndrome, such as active tuberculosis and HIV infection.
- •Allograft requires immunosuppressive therapy or other major immunosuppressive therapies.
- •Severe serious wounds, ulcers or fractures.
- •Clinical evaluation is unacceptable
研究组 & 干预措施
Phase 1 (Drug Tolerance Evaluation)
Using a 3 + 3 trial design, bortezomib dose exploration was performed to determine the stage 2 bortezomib dose. The number of participants at this stage is 6-9.
干预措施: mFOLFIRINOX (Drug)
Phase 1 (Drug Tolerance Evaluation)
Using a 3 + 3 trial design, bortezomib dose exploration was performed to determine the stage 2 bortezomib dose. The number of participants at this stage is 6-9.
干预措施: Bortezomib Injection (Drug)
Phase 1 (Drug Tolerance Evaluation)
Using a 3 + 3 trial design, bortezomib dose exploration was performed to determine the stage 2 bortezomib dose. The number of participants at this stage is 6-9.
干预措施: Sintilimab (Drug)
Phase 2 (Dose extension)
Phase 2: This phase will adopt competitive enrollment, and the Bayesian prediction probability method will be used to monitor the main efficacy index of the trial ORR in real time to determine the early termination or continue the trial. A maximum number of 57 patients were enrolled in this stage.
干预措施: Bortezomib Injection (Drug)
Phase 2 (Dose extension)
Phase 2: This phase will adopt competitive enrollment, and the Bayesian prediction probability method will be used to monitor the main efficacy index of the trial ORR in real time to determine the early termination or continue the trial. A maximum number of 57 patients were enrolled in this stage.
干预措施: Sintilimab (Drug)
Phase 2 (Dose extension)
Phase 2: This phase will adopt competitive enrollment, and the Bayesian prediction probability method will be used to monitor the main efficacy index of the trial ORR in real time to determine the early termination or continue the trial. A maximum number of 57 patients were enrolled in this stage.
干预措施: mFOLFIRINOX (Drug)
结局指标
主要结局
Phase 1: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
时间窗: Up to 2 years.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0，including Complete Blood Count, liver function, renal function lab test and other blood test will be evaluated by using CTCAE 5.0 during study.
Phase 2: Objective reponse rate (ORR)
时间窗: Up to 2 years
The proportion of patients who had tumor evaluated as PR according to RECIST1.1 criteria during phase 2
次要结局
- Disease control rate (DCR)(Up to 2 years)
- Progression-free survival （PFS）(Up to 2 years)
- Duration of remission （DoR）(Up to 2 years)
- Overall survival (OS)(Up to 2 years)
研究者
TingBo Liang
Professor
Zhejiang University