Phase IB/Randomized Phase II Study of Folfirinox Plus AMG-479 (Ganitumab) or Placebo in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Dose-limiting toxicity (phase I)
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin calcium, irinotecan hydrochloride, 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 ganitumab, 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 cancer-killing substances to them. It is not yet known whether giving more than one drug (combination chemotherapy) is more effective with or without ganitumab in treating patients with pancreatic cancer.
PURPOSE: This phase I/II trial is studying the best dose of combination chemotherapy and ganitumab and how well combination chemotherapy with or without ganitumab works in treating patients with previously untreated metastatic pancreatic cancer.
详细描述
OBJECTIVES:
Primary
- To assess the safety and determine the maximally tolerated dose (MTD) of modified FOLFIRINOX (mFOLFIRINOX) and ganitumab in patients with previously untreated, metastatic pancreatic adenocarcinoma. (phase I)
- To compare overall survival of patients with previously untreated, metastatic pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX plus placebo. (phase II)
- To assess the convergent validity of each selected PRO-CTCAE item by comparing each item at baseline between patients with ECOG performance status (PS) 0 vs 1. (phase II)
Secondary
- To compare objective response rate, duration of response, and progression-free survival of patients with previously untreated, metastatic pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX plus placebo.
- To compare treatment-related toxicity in patients with previously untreated, metastatic pancreatic adenocarcinoma who receive mFOLFIRINOX plus ganitumab versus mFOLFIRINOX plus placebo.
- To assess the responsiveness (sensitivity to change) of Patient-Reported Outcomes (PRO)-CTCAE by comparing change scores within groups of patients as defined by changes in ECOG PS at post-baseline administrations. (phase II)
- To compare the maximum post-baseline score for each PRO-CTCAE item per patient between arms in the randomized phase II component of the study. (exploratory).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
Arm I
Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: ganitumab (Biological)
Arm I
Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: fluorouracil (Drug)
Arm I
Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: irinotecan hydrochloride (Drug)
Arm I
Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: leucovorin calcium (Drug)
Arm I
Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 48 hours beginning on day 2 (mFOLFIRINOX) and ganitumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
干预措施: oxaliplatin (Drug)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: fluorouracil (Drug)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: irinotecan hydrochloride (Drug)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: leucovorin calcium (Drug)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: oxaliplatin (Drug)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: placebo (Other)
Arm II
Patients receive mFOLFIRINOX as in arm I and placebo IV over 30-60 minutes on day 1.
干预措施: questionnaire administration (Other)
结局指标
主要结局
Dose-limiting toxicity (phase I)
Maximum-tolerated dose (phase I)
Overall survival (phase II)
Convergent validity of each selected PRO-CTCAE item (phase II)
次要结局
- Objective response rate and duration of response between the mFOLFIRINOX plus ganitumab and the mFOLFIRINOX plus placebo arms (phase II)
- Progression-free survival (phase II)
- Responsiveness (sensitivity to change) of PRO-CTCAE (phase II)