NCT00503724已完成1 期
Phase I and Pharmacokinetic Study of Enzastaurin (LY317615) in Children and Adolescents With Refractory Primary CNS Tumors
Pediatric Brain Tumor Consortium16 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2007年6月1日最近更新:
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 16
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
RATIONALE: Enzastaurin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and best dose of enzastaurin in treating young patients with refractory primary brain tumors.
详细描述
OBJECTIVES:
Primary
- To estimate the maximum tolerated dose (MTD) and/or recommend a phase II dose of enzastaurin hydrochloride in children with recurrent or refractory CNS tumors who are not receiving enzyme-inducing anticonvulsants.
- To further characterize the pharmacokinetics and toxicity of the recommended phase II dose of enzastaurin hydrochloride given twice daily in these patients.
Secondary
- To characterize the pharmacokinetics of enzastaurin hydrochloride at the recommended phase II dose given once a day or twice a day in children.
- To document and describe toxicities associated with enzastaurin hydrochloride.
- To document antitumor activity in children with recurrent or refractory CNS tumors.
- To explore changes in MR perfusion scans obtained within 15 ± 2 days after initiation of enzastaurin hydrochloride therapy as compared to baseline and to correlate these changes with clinical outcome.
- To evaluate a panel of biological surrogate markers in this patient population at baseline and following enzastaurin hydrochloride administration.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed primary CNS malignancy including low-grade glioma
- •All tumors, except intrinsic brain stem and diffuse optic pathway tumors, must have histological verification at either the time of diagnosis or recurrence
- •Patients with intrinsic brain stem or diffuse optic pathway tumors must have clinical and/or radiographic evidence of progression
- •Recurrent or progressive disease or disease refractory to standard therapy and for which there is no known curative therapy
- •PATIENT CHARACTERISTICS:
- •Inclusion Criteria:
- •Karnofsky performance scale (for > 16 years of age) or Lansky performance score (for ≤ 16 years of age) ≥ 60% assessed within two weeks prior to registration
- •Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL
- •Platelet count ≥ 100,000/μL (transfusion independent)
- •Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)
- •Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age as follows:
- •0.8 mg/dL (≤ 5 years of age)
- •1.0 mg/dL (6 to 10 years of age)
- •1.2 mg/dL (11 to 15 years of age)
- •1.5 mg/dL (≥ 16 years of age)
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
- •ALT ≤ 5 x ULN for age
- •Serum albumin ≥ 2.5 g/dL
- •Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
- •Negative pregnancy test
- •Patients must have a normal QTc for age and no evidence of a clinically significant arrhythmia on ECG
- •No evidence of active graft-versus-host disease
排除标准
- •Pregnant or lactating
- •Body surface area < 0.5 m^2
- •Clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
- •Known hypersensitivity to enzastaurin hydrochloride or its components
- •Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
- •PRIOR CONCURRENT THERAPY:
- •Inclusion Criteria:
- •Must have recovered from the acute toxic effects (grade ≤ 2) of all prior therapy before entering this study
- •Must not have received myelosuppressive chemotherapy within 3 weeks of entry onto this study (6 weeks for prior nitrosourea)
- •At least 7 days since the completion of therapy with a hematopoietic growth agent (i.e., filgrastim [G-CSF], sargramostim [GM-CSF], or erythropoietin)
- •At least 14 days since long-acting formulations
- •Therapeutic use of myeloid growth factors in patients with serious neutropenic conditions, such as sepsis, may be considered at the investigator's discretion
- •At least 7 days since the completion of therapy with a biologic agent
- •At least 2 weeks since prior local palliative radiotherapy (small port)
- •At least 6 months must have elapsed after prior total body irradiation (TBI) or craniospinal radiotherapy
- •At least 6 weeks must have elapsed after other substantial bone marrow irradiation
- •At least 6 months since prior allogeneic bone marrow transplantation
- •At least 3 months since prior autologous bone marrow or stem cell transplantation
- •Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration
- •Corticosteroids should be used at the lowest dose to control symptoms of edema and mass effect
- •Exclusion Criteria:
- •Routine concurrent use of growth factors (i.e., G-CSF, GM-CSF, or erythropoietin)
- •Any other concurrent anticancer or investigational drug therapy
- •Concurrent enzyme-inducing anticonvulsants (EIACDs)
- •Concurrent gents that prolong the QTc
- •Concurrent drugs that are substrates or inhibitors of CYP3A4 or CYP2C9
- •Other concurrent drugs that are sensitive substrates of CYP2C8, CYP2C9, or CYP2C19 and/or have a narrow therapeutic window
结局指标
主要结局
Maximum tolerated dose
时间窗: First 28 days of therapy
The maximum tolerated dose or recommended phase II dose will be based on the dose-limiting toxicities observed during the first 28 days of therapy in those participants receiving enzastaurin on a once per day dosing schedule.
Number of participants treated with the maximum tolerated dose or phase II recommended dose on a twice daily dosage schedule with dose-limiting toxicities
时间窗: First 28 days of therapy
次要结局
- Pharmacokinetics(Three days prior to course 1 and day 28 of course 1)
- Toxicity(From day 1 of therapy until 30 days after the last dose of the drug)
- Tumor response(Pre-treatment, day 15 of course 1, and at the end of courses 3, 5, 8, 11, and 13.)
- Change in MR perfusion parameters obtained within 15 ± 2 days after initiation of enzastaurin hydrochloride therapy as compared to baseline(Baseline and day 15 of course 1)
- Change from baseline in the inhibition of Akt cell signaling at day 14 and day 28(Pre-treatment and at days 14 and 28 of course 1)
- Akt pathway activity in pre-study tumor samples(Pre-treatment)
研究者
研究点 (16)
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