A Phase I/II Study of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Combination in Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Gemcitabine.
研究概览
简要总结
The purpose of this study is to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan (GAX-CI) in patients with metastatic pancreatic cancer.
详细描述
This was a two-part, single-institution, open-label, dose-escalation, phase 1/2 study to evaluate the clinical activity of gemcitabine, nab-paclitaxel, capecitabine, cisplatin, and irinotecan in patients with metastatic pancreatic cancer.
Part 1 of the study was a Phase 1 3 + 3 dose escalation study designed to evaluate the maximally tolerated dose (MTD) and safety of increasing doses of nab-paclitaxel in combination with gemcitabine, capecitabine, cisplatin, and irinotecan. There were two cohorts of dose escalations. The two cohorts differed based on the treatment cycle length (28 days for Cohort 1 and 21 days for Cohort 2). Dose escalation started with Cohort 1. Enrollment for Cohort 2 dose level 1 began once dose level 2 of Cohort 1 was shown to be safe and did not exceed MTD.
Part 2 was a Phase 2 expansion cohort study for the evaluation of efficacy once the MTD had been determined.
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 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically or cytologically confirmed untreated metastatic pancreatic adenocarcinoma.
- •Patients with the presence of at least one measurable lesion.
- •Male or non-pregnant and non-lactating female of age >18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
- •Must use acceptable form of birth control while on study.
- •Ability to understand and willingness to sign a written informed consent document.
排除标准
- •Patients who will be considered for surgery are ineligible.
- •Patient who have had any prior chemotherapy within 5 years of enrollment.
- •Patient who have had radiotherapy for pancreatic cancer.
- •Age ≥ 76 years
- •Patient who is receiving or have received any other investigational agents within 28 days prior to Day 1 of treatment in this study.
- •Patient who has undergone major surgery, other than diagnostic surgery within 28 days prior to Day 1 of treatment in this study.
- •Patient who has known brain metastases.
- •Patient with history of hypersensitivity or allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine, nab-paclitaxel, capecitabine, cisplatin, or irinotecan.
- •Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient who has serious medical risk factors involving any of the major organ systems.
- •Patient who has known history of infection with HIV, hepatitis B, or hepatitis C.
- •Pregnant or breast feeding.
- •Patient is unwilling or unable to comply with study procedures
- •Patient with clinically significant wound.
研究组 & 干预措施
Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 1, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 40 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 1, Dose level 2
Gemcitabine 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel 60 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID: PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin: 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 1, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel: 80 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin 20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 1, Dose level 4
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:100 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine:500 PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan:20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 1, Dose level 5
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 2, Dose level 1
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:40 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500 mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 2, Dose level 2
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:60 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Irinotecan (Drug)
Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Gemcitabine (Drug)
Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Capecitabine (Drug)
Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Cisplatin (Drug)
Phase 1, Cohort 2, Dose level 3
Gemcitabine: 500 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Nab-paclitaxel:80 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
Capecitabine:500mg BID, PO twice daily (BID); Days 1-14 of a 21 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 4 and 11 of a 21 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 4 and 11 of a 21 day cycle
干预措施: Irinotecan (Drug)
Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Nab-paclitaxel (Drug)
Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Gemcitabine (Drug)
Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Capecitabine (Drug)
Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Cisplatin (Drug)
Phase 2 Dose Expansion (Cohort 1, DL5)
Gemcitabine:500 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Nab-paclitaxel:125 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle
Cisplatin:20 mg/m^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle
Irinotecan: 20 mg/m^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle
干预措施: Irinotecan (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Gemcitabine.
时间窗: 28 days
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Gemcitabine: 500 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
Maximum Tolerated Dose (MTD) of Capecitabine.
时间窗: 28 days
Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use. Participants received Capecitabine: 500 mg BID, PO twice daily (BID); Days 1-7, 15-21 of a 28 day cycle (Cohort 1) or Days 1-14 of a 21 day cycle (Cohort 2)
Maximum Tolerated Dose (MTD) of Nab-paclitaxel.
时间窗: 28 days
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Nab-paclitaxel: 20, 40, 60, 80, 100,125 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
Maximum Tolerated Dose (MTD) of Cisplatin.
时间窗: 28 days
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Cisplatin:20 mg/m\^2, IV over 60 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
Maximum Tolerated Dose (MTD) of Irinotecan.
时间窗: 28 days
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m\^2. Participants received Irinotecan: 20 mg/m\^2, IV over 30 minutes; Days 1 and 15 of a 28 day cycle (Cohort 1) or Days 4 and 11 of a 21 day cycle (Cohort 2)
Progression-free Survival (PFS) Using RECIST 1.1 Criteria
时间窗: 27 months
PFS is defined as the number of months from the date of first dose to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
次要结局
- Safety of the Combination of Gemcitabine, Nab-paclitaxel, Capecitabine, Cisplatin, and Irinotecan (GAX-CI) in Patients With Untreated Metastatic PDA.(27 months)