Phase I Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo(Registered Trademark) (Vincristine Sulfate Liposomes Injection) in Children and Adolescents With Refractory Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Define the toxicity spectrum of Marqibo in children with cancer
研究概览
简要总结
Background:
- Marqibo(Registered Trademark) is a new anticancer drug. It combines Vincristine sulfate, which is a widely used anticancer drug, and packages it into a tiny fat bubble known as a liposome. The goal of this is to improve the drug's ability to destroy cancer cells and help reduce the potential side effects of treatment.
- Vincristine sulfate was originally developed from chemicals found in the periwinkle plant and acts against multiple types of malignant cancer. It is approved for multiple cancer types including solid tumors and blood cancers.
- Research has shown that Marqibo(Registered Trademark) is able to slow or stop the growth of cancer cells in some adults, both alone and in combination with other chemotherapy drugs, but more research is needed to determine its use in children.
- There has been one previous small study of Marqibo(Registered Trademark) in children. Although some anti-cancer activity was seen, side effects and optimal dosing were not fully determined.
- As is seen with standard Vincristine suflate, the most common side effect of Marqibo(Registered Trademark) involves the nervous system. It can cause numbness and tingling in the hands and feet. Symptoms commonly improve when the drug is discontinued or the dose is lowered.
Objectives:
- To determine the safety and efficacy of Marqibo as a treatment for children who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.
Eligibility:
- Children and adolescents between 2 and 21 years of age who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.
- These cancer types include solids tumors, primary brain tumors, leukemias, and lymphomas.
详细描述
BACKGROUND
- Vincristine sulfate is a widely used antineoplastic agent of the alkaloid class of drugs derived from the periwinkle plant (Vinca rosea Linn.). It has activity against a wide number of malignancies. It is a cell-cycle-specific agent that arrests cell growth in the M-phase (metaphase) by binding specifically with tubulin and disrupting cell division. Its dose limiting toxicity (DLT) is virtually always neurological.
- Investigations over the past two decades have demonstrated that liposomal drug carriers are capable of increasing the therapeutic index of anticancer drugs by altering the drug s pharmacological behavior.
- Marqibo(Registered Trademark) is vincristine encapsulated in sphingomyelin/cholesterol (SM/CHOL) liposomes, developed to increase the activity of vincristine. It has been shown to have activity in Phase 2 studies in adults. Previous investigation of Marqibo(Registered Trademark) in children is limited. A small phase 2 study was conducted with dosing of 2.0mg/m2 every 14 days. The agent appeared to be well tolerated and some activity was seen, although data were quite limited.
OBJECTIVES
- To define the maximum tolerated dose (MTD), toxicity profile, dose-limiting toxicities, and pharmacokinetics in children and adolescents with solid tumors or hematologic malignancies receiving weekly intravenous doses of Marqibo(Registered Trademark).
- To define the tolerability and potential activity of Marqibo(Registered Trademark) in children and adolescents with relapsed or refractory acute lymphoblastic leukemia (ALL) at the pediatric MTD.
ELIGIBILITY
研究设计
- 研究类型
- Interventional
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 20 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
Marqibo
Marqibo® (Vincristine sulfate liposomal) will be administered intravenously over 60 minutes (±10 minutes) every 7 days (±3 days) (Days 1, 8, 15, 22) for four doses (1 cycle). Cycles may be repeated every 28 days for a maximum of 6 cycles; additional cycles may be offered with evidence of acceptable toxicity and clinical benefit.
- The trial follows a rolling phase I design with 2 to 6 subjects per dose level and standard definitions of MTD and DLT. At the MTD, a total of 6 additional subjects with relapsed or refractory ALL will be evaluated.
- Detailed pharmacokinetic studies will be performed during the first treatment cycle
干预措施: Marqibo (Drug)
结局指标
主要结局
Define the toxicity spectrum of Marqibo in children with cancer
时间窗: up to 48 weeks
Toxicity was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0).
Determine of Marqibo® administered as a 60 minute intravenous infusion weekly (every 28 days constitute 1 cycle), in children and adolescents with refractory solid tumors and hematologic malignancies.
时间窗: up to 48 weeks
The MTD was defined as the dose level immediately below the dose level at which ≥2 subjects in a cohort of 2 to 6 subjects experienced a DLT.
Determine dose limiting toxicities (DLT) of Marqibo® administered as a 60 minute intravenous infusion weekly (every 28 days constitute 1 cycle), in children and adolescents with refractory solid tumors and hematologic malignancies.
时间窗: up to 48 weeks
DLT was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0). Adverse events (AEs) that were considered disease-related (not suspected of relationship to Marqibo) were not considered dose-limiting toxicities. Only those AEs deemed suspected of a relationship to Marqibo were used in the definition of DLT.
次要结局
- Evaluate the plasma pharmacokinetics of Marqibo in children with cancer.(28 days)