Phase II Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 主要终点
- Number of Participants With the Presence of Drug in the Tumor Tissue
研究概览
简要总结
Background:
The brain is separated from the rest of the blood stream by the blood-brain barrier. This is like a filter that protects the brain. But is also a challenge when medicines need to get into the brain. Researchers want to give the new drug LB100 to people before brain tumor surgery. They will measure how much LB100 is in the blood and how much gets into the brain. This may help with the use of LB100 to treat brain tumors in the future.
Objective:
To see if LB100 can pass into the brain.
Eligibility:
People at least 18 years old with a brain tumor that requires surgery.
Design:
Participants will be screened with:
Physical exam
Medical history
Blood tests
Neurosurgery evaluation
Scans
Heart tests
Tumor sample. This can be from a previous procedure.
Participants will have their brain surgery at the Clinical Center.
Participants will get a dose of the study drug through a plastic tube in a vein for 2 hours during surgery.
Participants will have blood taken 7 times in the 8 hours after getting the study drug.
Tumor samples will be taken during surgery.
Participants will have a heart test after getting the study drug. Sticky pads on the skin will measure electrical activity of the heart.
Two-three weeks after leaving the hospital, participants will have a follow-up visit. They will have a physical exam and blood tests.
One month after surgery, they will be contacted in person or by phone to see how they are doing.
详细描述
Background:
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Primary gliomas are an incurable disease in spite of aggressive multimodality therapy consisting of craniotomy, irradiation, and chemotherapy. Therapeutic options for patients with recurrent glioma are limited, and there is an unmet need to identify more effective agents.
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LB100, a water-soluble small molecule novel protein phosphatase 2A (PP2A) inhibitor, was commercially developed through a Cooperative Research and Development Agreement (CRADA) based on our previous intramural research. This compound has shown to be effective in a variety of cancer types in both in vitro and in vivo models. Preclinical studies indicate LB100 has in vitro and in vivo activity as a single agent as well as potentiating the effect of cytotoxic agents including temozolomide, docetaxel, doxorubicin, and ionizing radiation. LB100 is active in combination with temozolomide or doxorubicin against xenografts of glioblastoma, neuroblastoma, pheochromocytoma, breast cancer, fibrosarcoma, and melanoma.
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A complete phase I study of LB100 has established its safety and the recommended phase II dose (2.33 mg/m^2, daily for three days every 3 weeks).
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Although it is a polar compound, rodent studies suggest LB100 has activity in the brain.
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Whether LB100 can across the human blood brain barrier (BBB), and at what concentration relative to the plasma level is not known. Characterizing these parameters is important because:
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- Our ongoing in vitro studies indicate that LB100 has distinct mechanisms of action at different drug concentrations (e.g., nM versus uM);
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- There are other brain tumors lacking effective medical therapies but without a BBB. Characterizing the LB100 BBB penetration profile will assist in defining its optimal clinical indication.
Objective:
-To determine the pharmacokinetic (PK) properties of LB100 in glioma tumor tissues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
1/LB100 Protein Phosphatase 2A Inhibitor, in Recurrent Glioblastoma
Treatment with LB100
干预措施: LB-100 (Drug)
结局指标
主要结局
Number of Participants With the Presence of Drug in the Tumor Tissue
时间窗: an average of 5.5 hours after drug administration
Participants tumor tissue was examined to determine the presence of drug in the tumor tissue.
次要结局
- Plasma Concentration and Calculated LB100(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Maximum Observed Plasma Concentration of LB100 (Cmax)(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Concentration of LB100(average of 5.5 hours after infusion)
- Changes in Phospho-protein Expression in Circulating Peripheral Blood Mononuclear Cells (PBMC)(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Area Under the Plasma Concentration vs. Time Curve Extrapolated to Infinity (AUC(INF)(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Plasma Half-Life of Drug LB100(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Time to Maximum Observed Plasma Concentration of LMB100 (Tmax)(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Total Clearance (CL) of LMB100(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Volume of Distribution (Vd) of LMB100(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Brain Concentration(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
- Brain Penetration(Pre-dose; End of infusion (2 hours post-start); 30 minutes post LB100 infusion completion; 1 hour post LB-100 infusion completion; 2 hours post LB100 infusion completion; 4 hours post LB100 infusion completion; 8 hours post LB100 infusion completion)
研究者
Eric Burton
Principal Investigator
National Cancer Institute (NCI)