A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 211 Administered as Continuous Intravenous Infusion in Subjects With Relapsed/Refractory Gastrointestinal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this Phase 1 study is to determine if AMG 211 given as a continous intravenous (IV) infusion is safe and tolerable in adult participants that have advanced gastrointestinal adenocarcinoma. The study will be conducted in multiple sites and test increasing doses of AMG 211. The safety of participants will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests. Efficacy will be assessed by the usual imaging procedures and their interpretation.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent provided
- •18 years or older
- •Advanced relapsed/refracted gastrointestinal adenocarcinoma
- •At least 1 measurable tumor lesion
- •Tumor tissue available or is willing to undergo biopsy of a tumor lesion before the start of treatment
- •Adequate hematological, renal, and liver function
- •Body weight ≥ 45 kg
- •Other inclusion criteria may apply
排除标准
- •Malignancy other than gastrointestinal (GI) adenocarcinoma requiring current therapy
- •Evidence of uncontrolled systemic disease, active infection, Hepatitis B and/or C, human immunodeficiency virus (HIV), history of cardiac disease, history of significant central nervous system (CNS) disease, history of chronic autoimmune disease (with the exception of stable type 1 diabetes)
- •Major surgery within 28 days of study day 1
- •Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment in another investigational device or drug study. Other investigational procedures while participating in this study are excluded. Exception to this criterion is the participation in the optional Imaging Study and all procedures related to this study.
- •Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal therapy for cancer within 14 days prior to study entry and not recovered from treatment
- •Unresolved toxicities from prior anti-tumor therapy
- •Males or Females of reproductive potential, and unwilling to practice an acceptable method of effective birth control while on study through 30 days after receiving the last dose of study drug
- •Females who are pregnant, planning to become pregnant, lactating/breastfeeding or who plan to breastfeed while on study through 30 days after receiving the last dose of study drug
- •Other exclusion criteria may apply
研究组 & 干预措施
AMG 211 200 μg/day for 7/14 Days
In cycle 1 participants receive 200 µg/day AMG 211 administered as a continuous intravenous infusion (cIV) infusion at a constant flow rate for 7 days followed by a 3-week treatment-free interval. In cycle 2 and thereafter, participants receive 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 200 μg/day for 14 Days
Participants receive 200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 400 μg/day for 14 Days
Participants receive 400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 800 μg/day for 14 Days
Participants receive 800 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 1600 μg/day for 14 Days
Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 1600 µg/day for 28 Days
Participants receive 1600 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 3200 µg/day for 14 Days
Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 3200 µg/day for 28 Days
Participants receive 3200 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 6400 µg/day for 14 Days
Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 14 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 6400 µg/day for 28 Days
Participants receive 6400 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
AMG 211 12,800 µg/day for 28 Days
Participants receive 12,800 µg/day AMG 211 administered as a cIV infusion for 28 days followed by a 2-week treatment-free interval.
干预措施: AMG 211 (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: 28 days
A DLT was defined as any of the following occurring during the first 28 days of treatment and regarded by the investigator and/or sponsor as related to AMG 211. Hematological DLTs: absolute neutrophil count (ANC) \< 0.5 × 10⁹ cells/L for ≥ 7 days; febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infection) with ANC \< 0.5 × 10⁹ cells/L and fever ≥ 38.5°C; platelets \< 25 × 10⁹ cells/L ≥ 7 days. Non-hematological DLTs: any AMG 211-related ≥ grade 3 non-hematological toxicity, excluding nausea and vomiting not refractory to anti-emetics, flare-up of pain due to potential increase in tumor volume, cytokine release syndrome manageable with symptomatic treatment and/or infusion interruption of up to 2 days. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to assess toxicities/adverse events.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug through end of treatment + 30 days (median time frame was 75.5 days).
An adverse event (AE) was defined as any untoward medical occurrence, which does not necessarily have a causal relationship with study treatment. A serious adverse event (SAE) was defined as an event that: was fatal or life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/borth defect; or other significant medical event. A TEAE was defined as any AE starting on or after the first dose of study drug and up to and including 30 days after the end of last dose of study drug. The severity of each adverse event was graded using CTCAE version 4.03 criteria (1=mild, 2=moderate, 3=severe, 4=life-threatining, 5=death). 'Any TEAE' includes both serious and non-serious TEAEs.
次要结局
- Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Maximum Observed Concentration (Cmax) of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Area Under the Serum Concentration-Time Curve (AUC) From Time 0 to the Last Quantifiable Concentration in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUCinf) in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Terminal Half-life (T1/2) of AMG-211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Terminal Half-life of AMG-211 in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion)
- Concentration of AMG 211 at Steady State (Css) in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Serum Clearance of AMG 211 in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 7 or 14 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 (for 14-day dosing groups only) hours after the start of infusion, at the end of infusion (Day 8 or Day 15), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Volume of Distribution at Steady-state (Vss) in Cycle 1 in Participants Who Received Dosing for 28 Days(Cycle 1: Predose, 2, 6, 24, 48-96, and 168 hours after the start of infusion, Day 15, at the end of infusion (Day 29), and 0.5, 2, 4, 8, and 24 hours after the end of infusion.)
- Number of Participants With Anti-AMG 211 Antibody Formation(Predose and 24 hours after the end of infusion during each treatment cycle, until 4 weeks after the last dose. Median time frame was 75.5 days.)
- Number of Participants With an Overall Objective Response(Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.)
- Duration of Response(Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.)
- Time to Response(Disease response was assessed every second cycle (8-10 weeks) until 4 weeks after the last dose. The median time frame was 75.5 days.)
- Time to Tumor Progression in Participants Treated at the Maximum Tolerated Dose (MTD)(From first dose of AMG 211 until tumor progression, assessed through the end of study (up to 4 weeks after the last dose). The median time frame was 75.5 days.)
- Progression Free Survival (PFS) at 6 Months in Participants Treated at the MTD(6 months)