A Phase 1 Study Of Ramucirumab, a Human Monoclonal Antibody Against the Vascular Endothelial Growth Factor-2 (VEGFR-2) Receptor in Children With Refractory Solid Tumors, Including CNS Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 21
- 主要终点
- Number of Participants With Anti-Ramucirumab Antibodies
研究概览
简要总结
The main purpose of this study is to evaluate the safety of the study drug known as ramucirumab in children with recurrent or refractory solid tumors including central nervous system (CNS) tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A: participants with recurrent or refractory non-CNS solid tumors
- •Part B: participants with recurrent or refractory CNS tumors
- •Measurable or evaluable disease
- •No other therapeutic options
- •Performance Status: Karnofsky ≥50% for participants >16 years and Lansky ≥50 for participants ≤16 years
排除标准
- •Active or recent history of serious bleeding events
- •Active or recent history of gastrointestinal perforations, ulcers, fistulas or abscesses
- •Active or recent history of hypertensive crisis or hypertensive encephalopathy
- •Active non-healing wound or bone fracture
- •History of solid organ transplant
研究组 & 干预措施
Ramucirumab
(Part A-Non-CNS Solid Tumors) Escalating doses of 8 milligrams per kilogram (mg/kg) or 12 mg/kg Ramucirumab administered as an intravenous infusion every 2 weeks (Q2W) with 3 doses per 42 day cycle.
(Part B-CNS Tumors) Participants received 12 mg/kg Ramucirumab as an intravenous injection Q2W with 3 doses per cycle.
干预措施: Ramucirumab (Drug)
结局指标
主要结局
Number of Participants With Anti-Ramucirumab Antibodies
时间窗: Predose Cycle 1 Day 1 through Follow-Up (Up to 42 Months)
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. A treatment-emergent anti-drug antibodies (TEADA) sample was defined as: a post treatment sample with at least a 4-fold increase in titer from pre treatment sample; or 1:20 post treatment titer for participants that had no detectable ADA titer at baseline.
Part A: Number of Participants With Dose Limiting Toxicities (DLTs): Maximum Tolerated Dose of Ramucirumab
时间窗: Baseline to Study Completion (Up to 42 Months)
A DLT is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0: 1. Any death not clearly due to the underlying disease or extraneous causes 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity 3. Grade ≥4 neutropenia or thrombocytopenia \>7 days 4. Grade ≥3 thrombocytopenia with bleeding 5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care 6. Grade ≥3 fatigue ≥1 week 7. Grade ≥3 electrolyte abnormality that lasts\>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT. 8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Population Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab
时间窗: Predose, Cycle 1 Day 1 (end of infusion (EOI), 1 hour after EOI) and Cycle 1 Day 43 (1 hour after EOI)
Population Pharmacokinetics (PK): Minimum observed plasma concentration of Ramucirumab.
次要结局
- Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)(Baseline to Date of Objective Disease Progression (Up to 42 Months))
- Overall Survival(Baseline to Date of Death from Any Cause (Up to 42 Months))
- Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)(Baseline to Date of Objective Disease Progression (Up to 42 Months))
- Duration of Response (DOR)(Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 42 Months))