A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) With or Without Interferon Gamma in Patients With Refractory Pediatric Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Pharmacokinetics
研究概览
简要总结
Background
- HGS-ETR2 is a monoclonal antibody, produced in the laboratory from human genes.
- HGS-ETR2 targets a protein called the TRAIL receptor that is located on the surface of some tumor cells. When the TRAIL receptor is activated, it can cause the tumor cell to self-destruct.
Objectives:
- To determine the highest dose of HGS-ETR2 that can be given safely in children and young adults with cancer.
- To study the pharmacology (how the body handles the drug) of HGS-ETR2 by measuring the amount of drug in the bloodstream over time before and after a dose is given to the patient.
- To determine if HGS-ETR2 can stop or slow tumor growth.
- To determine whether proteins in tumor tissue before treatment can predict whether the tumor will respond to HGS-ETR2 therapy.
Eligibility:
-Patients 1 to 21 years of age with solid cancers that do not respond to standard therapy.
Design:
- HGS-ETR2 is given through a vein (intravenously, IV) once every 14 days. Each treatment cycle is 28 days long and consists of two doses of HGS-ETR2.
- The dose of HGS-ETR2 is increased in successive small groups of patients until the maximum tolerated dose (highest dose with acceptable side effects) is determined.
- During the treatment period, patients have a physical examination at least once a week, and routine blood tests at least twice a week. These tests are done less frequently in later treatment cycles.
- Additional blood samples are drawn for immunology and pharmacology studies.
- Tests to monitor the size of the tumor (X-rays, CT scans, MRI, PET scans) are done periodically throughout the treatment period.
- Patients may continue to receive HGS-ETR2 until unacceptable side effects develop or the tumor grows.
详细描述
Background:
Pediatric solid tumors represent approximately one fourth of cancer diagnoses in children. Despite intensive regimens, patients with metastatic or recurrent tumors have unsatisfactory survival rates. Therefore new therapies are needed to improve outcomes.
Members of the TNF ligand superfamily induce death in tumor cells through direct ligation of death receptors and apoptosis induction.
TRAIL (TNF-related apoptosis inducing ligand) has specific anti-tumor activity against a wide range of tumor cells without inducing death in normal cells. TRAIL-induced apoptosis has been demonstrated in a wide variety of pediatric solid tumors, including Ewing's sarcoma, osteosarcoma, neuroblastoma, and rhabdomyosarcoma.
HGS-ETR2 (Human Genome Sciences; human monoclonal antibody) is a fully human monoclonal antibody that agonistically binds TRAIL receptor 2 and, like TRAIL itself, induces apoptosis in a variety of malignant cell types with little effect on normal cells.
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
- 1 Year 至 30 Years（Child, 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
1
Lexatumumab alone dose escalation
干预措施: Lexatumumab alone (Drug)
2
Lexatumumab with interferon - dose escalation
干预措施: Lexatumumab in combination (Drug)
2
Lexatumumab with interferon - dose escalation
干预措施: Interferon gamma 1b in combination (Drug)
3
Lexatumumab 10mg/kg with interferon expansion at
干预措施: Lexatumumab in combination (Drug)
3
Lexatumumab 10mg/kg with interferon expansion at
干预措施: Gamma 1b potential expansion (Drug)
结局指标
主要结局
Pharmacokinetics
时间窗: 2 years
MTD of lexatumumab w/interferon gamma 1b
时间窗: 6 months
Asult MTD and DLTs of lexatumumab
时间窗: 6 months
次要结局
- Determine if anti-HGS-ETR2 antibodies are produced(2 years)
- Correlation of immunohistochemical expression of pro-apoptotic proteins with response to therapy(2 years)
- Tumor response rate(2 years)