Preoperative Extended Chemotherapy vs. Chemotherapy Plus Hypofractionated Radiation Therapy for Borderline Resectable Adenocarcinoma of the Head of the Pancreas
试验速览
- 阶段
- 2 期
- 入组人数
- 126
- 试验地点
- 155
- 主要终点
- Overall Survival (OS) Rate
研究概览
简要总结
This randomized phase II trial studies how well combination chemotherapy (mFOLFIRINOX) with or without hypofractionated radiation therapy before surgery works in patients with pancreatic cancer that can be removed by surgery. Drugs used in combination chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, and irinotecan hydrochloride, 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. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. It is not yet known if combination chemotherapy is more effective with or without hypofractionated radiation therapy before surgery in treating patients with pancreatic cancer.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate and estimate 18 months overall survival (OS) rate of patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) receiving neoadjuvant therapy.
SECONDARY OBJECTIVES:
I. To evaluate and estimate the R0 resection rates in patients receiving each of the two multimodality treatment regimens.
II. To evaluate and estimate the event-free survival in patients receiving each of the two multimodality treatment regimens.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmation of radiographic stage as borderline resectable disease by real-time Alliance central radiographic review
- •No prior chemotherapy or radiation for pancreatic cancer
- •No definitive resection of pancreatic cancer
- •Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
- •Chronic concomitant treatment with strong CYP3A4 inducers is not allowed; patients must discontinue the drug 14 days prior to the start of study treatment
- •No grade >= 2 neuropathy
- •No known Gilbert's syndrome or known homozygosity for UGAT1A1*28 polymorphism
- •No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease) within 28 days of registration
- •Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •Platelet count >= 100,000/mm^3
- •Creatinine =< 1.5 x upper limit of normal (ULN) or
- •Calculated (calc.) creatinine clearance > 45 mL/min
- •Total bilirubin =< 2.0 mg/dL
- •Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 X upper limit of normal (ULN)
排除标准
- 未提供
研究组 & 干预措施
mFOLFIRINOX + surgery + FOLFOX
Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: surgery (Procedure)
mFOLFIRINOX + surgery + FOLFOX
Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: mFOLFIRINOX (Drug)
mFOLFIRINOX + surgery + FOLFOX
Patients receive 8 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: FOLFOX (Drug)
mFOLFIRINOX + radiation + surgery + FOLFOX
Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: radiation therapy (Radiation)
mFOLFIRINOX + radiation + surgery + FOLFOX
Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: surgery (Procedure)
mFOLFIRINOX + radiation + surgery + FOLFOX
Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: mFOLFIRINOX (Drug)
mFOLFIRINOX + radiation + surgery + FOLFOX
Patients receive 7 cycles of mFOLFIRINOX. One cycle is 14 days. mFOLFIRINOX consists of oxaliplatin, irinotecan, leucovorin and 5-FU. Patients receive radiation therapy then undergo surgery and receive 4 cycles of FOLFOX 4-12 weeks after surgery. FOLFOX consists of oxaliplatin, leucovorin and 5-FU.
干预措施: FOLFOX (Drug)
结局指标
主要结局
Overall Survival (OS) Rate
时间窗: 18 months
Defined as the percentage of patients who are alive at 18 months after randomization divided by the total number of evaluable patients in each arm. An evaluable patient is defined as any patient who signed informed consent, deemed eligible by central review and received any protocol-defined treatment. 95% confidence interval will be estimated based on standard method. Chi-squared test (or Fisher's exact test if the data in contingency table is sparse) will be used to compare 18 month OS rates among treatment arms. OS within each arm will be summarized by Kaplan-Meier method. Median, 1-year and 2-year rates will be estimated based on Kaplan-Meier curves.
次要结局
- Residual Tumor (R)0 Resection Rate(24 months)
- Event-free Survival(4 years and 7 months)
- Pathologic Complete Rate (pCR) Rate(24 months)
- Incidence of Adverse Events Assessed Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4 and the Patient-Reported Outcomes Version of the CTCAE(1 year)