A Pilot and Feasibility Study of PD-1 Blockade With Nivolumab in Combination With Chemotherapy in Patients With Borderline Resectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (mFFX) chemotherapy
研究概览
简要总结
This pilot and feasibility study studies how well nivolumab and combination chemotherapy work before surgery in treating patients with pancreatic cancer that could possibly be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab in combination with chemotherapy before surgery may work better in treating patients with pancreatic cancer compared to chemotherapy alone.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate development of clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (FFX).
II. To evaluate pathologic complete response after neoadjuvant nivolumab and FOLFIRINOX (FFX).
SECONDARY OBJECTIVES:
I. To evaluate early efficacy measured by percent change of CA 19-9 response rate, R0 resection rate, overall response rate (ORR) and disease free survival (DFS).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed pancreatic adenocarcinoma
- •One of the following:
- •Borderline resectable disease. There are multiple definitions of borderline resectable pancreatic ductal adenocarcinoma (PDAC) including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on computed tomography (CT):
- •An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring >= 180 degrees of the circumference of the vessel wall
- •Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
- •Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
- •An interface between the tumor and superior mesenteric artery (SMA) measuring < 180 degrees of the circumference of the vessel wall
- •Performance status of Eastern Cooperative Oncology Group (ECOG) of 0-1
- •Therapy naive
- •Absolute neutrophil count (ANC) >= 1500/mm^3
- •Platelets >= 100,000/mm^3
- •Hemoglobin >= 9 g/dl
- •Serum total bilirubin =< 1.5 x upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x ULN
- •Alkaline phosphatase =< 2.5 x ULN
- •Serum creatinine (sCr) =< 1.5 x ULN or creatinine clearance (Ccr) >= 40 mL/min as calculated by the modified Cockcroft-Gault formula
- •Peripheral neuropathy < grade 2
排除标准
- •Locally advanced (clearly unresectable) or metastatic disease
- •Known status of human immunodeficiency virus (HIV) which is not well-controlled at the time of study eligibility
- •Untreated hepatitis B infection
- •Active infection or antibiotics within 48 hours prior to study
- •Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (patients with history of skin cancers excluding melanoma will be eligible for participation)
- •Serious medical comorbidities such as New York Heart Association class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
- •Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a grade 2 or greater bleeding episode in the 3 weeks before day 1
- •Prior history of cerebrovascular accident or transient ischemic attack, or pre-existing carotid artery disease
- •Known pregnancy, nursing women or positive pregnancy test. Requirement for women of childbearing potential (WOCBP) must have a pregnancy test every 4 weeks and WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab
- •Any prisoners, or subjects who are compulsory detained are excluded
- •Any condition that would preclude informed consent, consistent follow-up and compliance for the study participation
研究组 & 干预措施
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Fluorouracil (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Irinotecan Hydrochloride (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Leucovorin Calcium (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Nivolumab (Biological)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Oxaliplatin (Drug)
Treatment (nivolumab, mFOLFIRINOX)
Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.
干预措施: Therapeutic Conventional Surgery (Procedure)
结局指标
主要结局
Clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (mFFX) chemotherapy
时间窗: Up to 3 years
Descriptive statistics with frequency and proportion will be used.
Pathologic complete response after nivolumab and mFFX treatment
时间窗: Up to 3 years
Descriptive statistics with frequency and proportion will be used.
次要结局
- R0 resection rate(Up to 3 years)
- Percent change of CA 19-9 response rate(Baseline up to 3 years)
- Overall response rate (ORR)(Up to 3 years)
- Wound infection(Up to 3 years)
- Delayed wound healing(Up to 3 years)
- Disease free survival (DFS)(Up to 3 years)
- Incidence of adverse events(Up to 28 days after last dose of study drug)
- Wound dehiscence(Up to 3 years)