A Sequential Phase I Study Of The Combination Of Everolimus (Rad001) With 5-Fu/Lv (De Gramont), Folfox6, And Folfox6/Panitumumab In Patients With Refractory Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab
研究概览
简要总结
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving everolimus together with combination chemotherapy and/or panitumumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with fluorouracil, leucovorin, panitumumab, and oxaliplatin in treating patients with solid tumors that did not respond to previous treatment.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab in patients with refractory solid tumors.
Secondary
- To determine the adverse event profile of these regimens.
- To correlate response with S6-phosphorylation and AKT-phosphorylation in available archived tumor samples.
- To evaluate preliminary evidence of antitumor activity of these regimens using RECIST criteria for a subset of patients with measurable disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Group 1
Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: everolimus (Drug)
Group 1
Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Group 1
Patients receive oral everolimus once daily on days 1-28. Patients also receive leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: leucovorin calcium (Drug)
Group 2
Patients receive oral everolimus once daily on days 1-28 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: panitumumab (Biological)
Group 2
Patients receive oral everolimus once daily on days 1-28 and panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: everolimus (Drug)
Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: panitumumab (Biological)
Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: everolimus (Drug)
Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: leucovorin calcium (Drug)
Group 3
Patients receive oral everolimus once daily on days 1-28, leucovorin calcium IV followed by fluorouracil IV continuously over 46 hours beginning on day 1, and oxaliplatin IV over 2-4 hours on day 1. Some patients may also receive panitumumab IV over 30-90 minutes on day 1. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
结局指标
主要结局
Maximum tolerated dose of everolimus in combination with sequential fluorouracil (5-FU) and leucovorin calcium, panitumumab, modified 5-FU, leucovorin calcium, and oxaliplatin (mFOLFOX6), and mFOLFOX6 with panitumumab
时间窗: after the first 28 day cycle
Patients will be assessed for toxicity at the commencement of each cycle
Toxicity as assessed by CTC version 3.0 at the beginning of each treatment course
时间窗: first 28 day cycle
Dose Limiting Toxicities (DLT) are defined during the first cycle (28 days).
Tumor response
时间窗: Every 8 weeks during treatment
Tumor response will be assessed by RECIST criteria
Correlation of response with S6-phosphorylation and AKT-phosphorylation in archived tumor samples
时间窗: 3 years
次要结局
未报告次要终点