S1313, A Phase IB/II Randomized Study of Modified FOLFIRINOX + Pegylated Recombinant Human Hyaluronidase (PEGPH20) Versus Modified FOLFIRINOX Alone in Patients With Good Performance Status Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 153
- 主要终点
- Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX
研究概览
简要总结
This partially randomized phase I/II trial studies the side effects and best dose of pegylated recombinant human hyaluronidase (PEGPH20) when given together with combination chemotherapy and to see how well they work compared with combination chemotherapy alone in treating patients with newly diagnosed pancreatic cancer that has spread to other places in the body. Pegylated recombinant human hyaluronidase may help chemotherapy drugs work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, irinotecan hydrochloride, 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. It is not yet known whether combination chemotherapy is more effective with or without pegylated recombinant human hyaluronidase in treating pancreatic cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety of modified leucovorin calcium, fluorouracil, irinotecan hydrochloride and oxaliplatin (mFOLFIRINOX) in combination with PEGPH20 and select the optimal dose of PEGPH20 for the phase II portion in patients with metastatic pancreatic adenocarcinoma. (Phase I) II. To assess the overall survival of patients with metastatic pancreatic adenocarcinoma treated with mFOLFIRINOX + PEGPH20 compared to those treated with mFOLFIRINOX alone. (Phase II)
SECONDARY OBJECTIVES:
I. To assess progression free survival (PFS) in patients receiving mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.
II. To assess objective tumor response (confirmed and unconfirmed, complete and partial) in patients with measurable disease treated with mFOLFIRINOX with PEGPH20 and patients receiving mFOLFIRINOX alone in this patient population.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
干预措施: 5-fluorouracil (Drug)
Phase II: mFOLFIRINOX
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Oxaliplatin (Drug)
Phase II: mFOLFIRINOX
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
Phase II: mFOLFIRINOX
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
Phase II: mFOLFIRINOX
Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and irinotecan hydrochloride IV over 1.5 hours on day 2, and 5-fluorouracil (5-FU) IV over 46 hours on days 2-4. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: 5-fluorouracil (Drug)
Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: PEGPH20 (Drug)
Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Oxaliplatin (Drug)
Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Leucovorin (Drug)
Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: Irinotecan (Drug)
Phase II: mFOLFIRINOX + PEGPH20
Patients receive pegylated recombinant human hyaluronidase (PEGPH20) IV over 10 minutes on day 1 and oxaliplatin, leucovorin calcium, irinotecan hydrochloride, and 5-fluorouracil (5-FU) as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: 5-fluorouracil (Drug)
Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
干预措施: PEGPH20 (Drug)
Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
干预措施: Oxaliplatin (Drug)
Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
干预措施: Leucovorin (Drug)
Phase I
PEGPH20, 3 ug/kg on Day 1 and Day 3/4, IV over 15 minutes; Oxaliplatin, 85 mg/m^2, on Day 2, IV over 2 hours; Leucovorin, 400 mg/m^2, on Day 2, IV over 2 hours; Irinotecan, 180 mg/m^2, on Day 2, IV over 1.5 hours; 5-fluorouracil (5-FU), 2,400 mg/m^2, Days 2-4, IV over 46 hours
干预措施: Irinotecan (Drug)
结局指标
主要结局
Phase I: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With mFOLFIRINOX
时间窗: 2 cycles of 14 days
Assess safety of mFOLFIRINOX in combination with PEGPH20 and select the optimal dose of PEGPH20 for the Phase II portion. MTD of PEGPH20 in combination with mFOLFORINOX was evaluated by testing decreasing doses of PEGPH20 from 3mcg/kg on Day 1 and Day 3/4, to 3mcg/kg on Day 1 only and to 1.6 mcg/kg on Day 1 only. MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 17%. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 4 absolute neutrophil count (ANC) anemia or thrombocytopenia; grade 4 ANC lasting \> 7 days; grade ≥ 3 febrile neutropenia; grade ≥ 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), total bilirubin, and creatinine; delay in starting the 2nd cycle of mFOLFIRINOX by \> 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4. Note: the third and lowest dose level was not reached.
Phase II: Overall Survival
时间窗: From date of registration to date of death due to any cause, assessed up to 3 years
Time from date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. Assessed using the logrank test.
次要结局
- Objective Tumor Response Rate (Confirmed and Unconfirmed, Complete and Partial)(Up to 3 years)
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Duration of treatment and follow up until death or 3 years post registration)
- Progression Free Survival (PFS) (Phase II)(From date of registration to date of death due to any cause, assessed up to 3 years)