A Phase II Study of R115777 (Zarnestra) (NSC # 702818, IND# 58,359) in Children With Recurrent or Progressive: High Grade Glioma, Medulloblastoma/PNET or Brainstem Glioma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 1
- 主要终点
- Incidence of adverse events graded according to NCI CTCAE version 3.0
研究概览
简要总结
This phase II trial is studying how well tipifarnib works in treating young patients with recurrent or progressive high-grade glioma, medulloblastoma, primitive neuroectodermal tumor, or brain stem glioma. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
详细描述
OBJECTIVES:
I. Determine the response rate in pediatric patients with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor (PNET), or brain stem glioma treated with tipifarnib.
II. Determine the distribution of time to progression, time to treatment failure, and time to death in patients treated with this drug.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to disease (high-grade glioma vs recurrent or progressive medulloblastoma/primitive neuroectodermal tumor [PNET] vs progressive diffuse, intrinsic brain stem glioma).
Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
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
- •Histologically confirmed brain tumor, including the following:
- •Anaplastic astrocytoma
- •Glioblastoma multiforme
- •Gliosarcoma
- •Anaplastic oligodendroglioma
- •Medulloblastoma/primitive neuroectodermal tumor (PNET)
- •Diffuse intrinsic brain stem glioma*
- •Progressive or relapsed disease after prior conventional therapy
- •Radiographic evidence of measurable disease
- •Performance status - Karnofsky 60-100% (over 16 years of age)
- •Performance status - Lansky 60-100% (16 years of age and under)
- •Performance status - ECOG 0-2
- •At least 8 weeks
- •Absolute neutrophil count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3 (transfusion independent)
- •Hemoglobin at least 8.0 g/dL (red blood cell transfusions allowed)
- •Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- •SGPT and SGOT less than 2.5 times ULN
- •Creatinine clearance OR radioisotope glomerular filtration rate at least 70 mL/min
- •Maximum creatinine based on age as follows:
- •0.8 mg/dL (5 years and under)
- •1.0 mg/dL (6 to 10 years)
- •1.2 mg/dL (11 to 15 years)
- •1.5 mg/dL (over 15 years)
- •Shortening fraction at least 27% by echocardiogram
- •Ejection fraction at least 50% by MUGA
- •No dyspnea at rest
- •No exercise intolerance
- •Pulse oximetry greater than 94%*
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •Seizure disorder is allowed provided it is well-controlled on non-enzyme-inducing anticonvulsants
- •No active graft-versus-host disease
- •No uncontrolled infection
- •No allergy to azoles (e.g., ketoconazole, itraconazole, or fluconazole)
- •Recovered from prior immunotherapy
- •At least 7 days since prior antineoplastic biologic agents
- •At least 1 month since prior autologous stem cell transplantation (SCT)
- •At least 6 months since prior allogeneic SCT
- •More than 1 week since prior growth factors
- •No concurrent immunomodulating agents
- •More than 2 weeks since prior myelosuppressive chemotherapy (4-6 weeks for nitrosoureas or temozolomide) and recovered
- •No concurrent anticancer chemotherapy
- •Concurrent dexamethasone allowed provided patient is on a stable or decreasing dose for at least 1 week prior to study entry
- •Concurrent corticosteroids allowed only for treatment of increased intracranial pressure
- •Recovered from prior radiotherapy
- •At least 2 weeks since prior local palliative radiotherapy (small port)
- •At least 3 months since prior craniospinal radiotherapy
- •At least 6 weeks since other prior substantial bone marrow radiotherapy
- 另有 76 项未显示
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
干预措施: tipifarnib (Drug)
结局指标
主要结局
Incidence of adverse events graded according to NCI CTCAE version 3.0
时间窗: Up to 2 years
Best objective tumor response rates (complete and partial response), based on MRIs
时间窗: Up to 2 years
Estimated ultimately as a simple binomial proportion. Estimated actuarially, using the product-limit (PL) estimate.
Time to tumor progression (TTP)
时间窗: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 2 years
The distribution of TTP will be analyzed using PL estimate.
Time to treatment failure (TTF)
时间窗: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 2 years
The distribution of TTF will be analyzed using PL estimate.
Time to death (TTD)
时间窗: Time from study enrollment to death from any cause, assessed up to 2 years
The distribution of TTD will be analyzed using PL estimate.
次要结局
未报告次要终点