A Phase 1b/2 Study to Evaluate the Safety and Efficacy of AMG 655 or AMG 479 in Combination With Gemcitabine as First-Line Therapy for Metastatic Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs; Phase 1b Portion Only)
研究概览
简要总结
This is a multi-center, 2-part study of AMG 655, AMG 479 or AMG 655-placebo plus gemcitabine as first-line treatment of subjects with metastatic pancreatic cancer. Part 1 is an open-label, dose-escalation phase 1b segment to determine the safety, tolerability and maximum tolerated dose of AMG 655 in combination with gemcitabine. Enrollment into part 1 of the study has been completed. Part 2 is a randomized, placebo-controlled phase 2 segment to estimate the efficacy as assessed by 6 month survival of AMG 655, AMG 479, or AMG 655-placebo in combination with gemcitabine. The phase 2 segment that will commence after dose selection in part 1. In part 2, subjects will be randomized 1:1:1 to AMG 655, AMG 479, or placebo in combination with gemcitabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Untreated metastatic adenocarcinoma of the pancreas (AJCC Stage IV)
- •Subjects with unresectable pancreatic cancer who have had surgery are eligible if fully recovered and greater than 30 days have elapsed since the surgery.
- •Subjects with a history of pancreatoduodenectomy are eligible provided that there is radiographically documented disease recurrence.
- •Men or women ≥ 18 years of age
- •Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
- •Adequate hematologic, hepatic, renal and coagulation function
- •Amylase and lipase ≤ 2.0 x ULN
- •Adequately controlled type 1 or 2 diabetic subjects
排除标准
- •Islet cell, acinar cell carcinoma, non-adenocarcinoma (eg, lymphoma, sarcoma, etc), adenocarcinoma originated from biliary tree or cystadenocarcinoma
- •Known central nervous system metastases
- •Uncontrolled cardiac disease or any other co-morbid disease that would increase the risk of toxicity
- •Adjuvant chemotherapy or chemoradiotherapy
研究组 & 干预措施
Phase 2 AMG 655
Subjects were treated with the dose of AMG 655 (10mg/kg) in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 655 infusion on days 1 and 15 after completion of the gemcitabine infusion.
干预措施: AMG 655 (Drug)
Phase 1b AMG 655 3mg/kg
Subjects were treated with one of 2 dose levels of AMG 655 (3 mg/kg) with gemcitabine.
干预措施: AMG 655 (Drug)
Phase 1b AMG 655 10mg/kg
Subjects were treated with one of 2 dose levels of AMG 655 (10 mg/kg) with gemcitabine.
干预措施: AMG 655 (Drug)
Phase 2 AMG 479
Subjects were treated with the dose of AMG 479 (12 mg/kg) in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 479 infusion on days 1 and 15 after completion of the gemcitabine infusion.
干预措施: AMG 479 (Drug)
Phase 2 AMG 655-placebo
Subjects were treated with the dose of AMG 655-placebo in combination with gemcitabine. Gemcitabine (1000 mg/m2) was administered by intravenous infusion on days 1, 8 and 15 of each 28 day cycle followed by the AMG 655-placebo infusion on days 1 and 15 after completion of the gemcitabine infusion.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs; Phase 1b Portion Only)
时间窗: 28 days
The incidence of adverse events and clinical laboratory abnormalities defined as DLTs. A DLT was defined as any grade 3 or higher hematologic or non-hematologic toxicity related to any study treatment.
Six Month Overall Survival Rate (Phase 2 Portion Only)
时间窗: 6 months
The proportion of subjects alive at 6 months
次要结局
- Objective Response Rate(From start of study treatment through up to 36 months)
- Progression-free Survival (PFS)(From start of study treatment through up to 36 months)
- Overall Survival(From start of study treatment through up to 36 months)
- Number of Subjects With an Adverse Event(From start of study treatment through up to 44 weeks)
- Pharmacokinetics of AMG 655, Ganitumab, and Gemcitabine(From start of study treatment through up to 48 weeks)
- Dose Intensity of Gemcitabine (Phase 2 Portion Only)(From start of study treatment through up to 40 weeks)
- Duration of Response(From objective response through up to 36 months)
- Incidence of Antibody Formation(From start of treatment up to 40 weeks)