Phase I/II Trial of Gefitinib and Radiation in Pediatric Patients Newly Diagnosed With Brain Stem Tumors or Incompletely Resected Supratentorial Malignant Gliomas With Phase II Limited to Brain Stem Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
研究概览
简要总结
Biological therapies such as gefitinib may interfere with the growth of the tumor cells and may make the tumor cells more sensitive to radiation therapy. This phase I/II trial is studying how well giving gefitinib together with radiation therapy works in treating children with newly diagnosed glioma.
详细描述
PRIMARY OBJECTIVES:
I. To define the safety of gefitinib administered in conjunction with irradiation in children with newly diagnosed non-disseminated diffuse intrinsic brainstem gliomas and newly diagnosed incompletely resected supratentorial malignant gliomas (STMG) not receiving enzyme inducing anticonvulsant drugs (EIACDs).
II. To define the safety of gefitinib in children with newly diagnosed, incompletely resected STMG receiving EIACDs.
III. To assess the safety and efficacy of gefitinib given with radiation therapy in children newly diagnosed with a brainstem glioma as measured by progression-free survival and to estimate the survival distribution.
SECONDARY OBJECTIVES:
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
- 3 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase I: newly diagnosed non-disseminated diffuse intrinsic brainstem tumor or newly diagnosed (diagnostic scan must be within 4 weeks prior to treatment initiation), incompletely resected supratentorial malignant glioma (anaplastic astrocytoma, glioblastoma multiforme or other high-grade glioma) (STMG); the STMG group must have residual tumor evident on postoperative MRI or CT
- •Phase II: only newly diagnosed non-disseminated diffuse intrinsic brain stem glioma patients are eligible
- •Performance status: Karnofsky or Lansky >= 50% assessed within two weeks prior to registration
- •Prior/concurrent therapy:
- •Chemotherapy: no prior therapy allowed, including prior gefitinib treatment
- •Radiation therapy (XRT): no prior therapy allowed
- •Bone marrow transplant: none prior
- •Anti-convulsants: patients with brain stem glioma (BSG) receiving EIACD will not be eligible; patients with STMG will be eligible for this study even if they are receiving enzyme inducting anti-convulsant drugs (EIACD) and will be stratified by use of EIACDs
- •Growth factors: off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
- •ANC > 1,000/ul
- •Platelets > 100,000/ul (transfusion independent)
- •Hemoglobin > 8g/dl (may be transfused)
- •Patients may have bone marrow involvement by disease
- •Creatinine < 2 x normal for age or GFR > 70 ml/min/1.73m^2
- •Bilirubin < 1.5 x normal institutional normal for age
- •SGPT (ALT) < 3 x institutional normal for age
- •Pregnant and/or lactating patients are excluded; patients of childbearing potential should not become pregnant and should not father a child during treatment with gefitinib; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- •Signed informed consent according to institutional guidelines must be obtained prior to study entry
排除标准
- •Patients with evidence of intramural hemorrhage on a scan obtained prior to enrollment or after enrollment, before treatment
- •Patients with BSG must not be taking enzyme-inducing anticonvulsant drugs
- •Patient must not be receiving any other anticancer or experimental drug therapy
- •Patient must have no uncontrolled infection
- •Patients with significant cardiac, hepatic, gastrointestinal, renal, pulmonary, or psychiatric disease are ineligible; patients with deep venous or arterial thrombosis within 6 weeks of study entry are ineligible
- •Patients with disseminated disease are not permitted
- •Patients with spinal disease requiring craniospinal radiation are not eligible
- •Patients with completely resected supratentorial malignant gliomas patients are ineligible
研究组 & 干预措施
Treatment (gefitinib and radiation therapy)
Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity.
Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.
干预措施: gefitinib (Drug)
Treatment (gefitinib and radiation therapy)
Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity.
Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.
干预措施: radiation therapy (Radiation)
Treatment (gefitinib and radiation therapy)
Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity.
Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.
干预措施: pharmacological study (Other)
Treatment (gefitinib and radiation therapy)
Phase I portion: Patients receive oral gefitinib once daily. Treatment repeats every 4 weeks for 13 courses (1 year). Patients also receive standard brain irradiation once daily, 5 days a week, for 6 weeks beginning concurrently with initiation of the first course of gefitinib. Treatment continues in the absence of disease progression or unacceptable toxicity.
Phase II portion: Once the MTD or the recommended Phase-II dose is determined, additional patients who have newly diagnosed BSG are treated at the MTD or the recommended Phase-II dose.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Number of Participants in Phase I Stratum 1A With Dose-limiting Toxicities (DLT) Observed During the First 8 Weeks of Gefitinib Therapy
时间窗: Day 1 of gefitinib therapy to end of week 8
The dose limiting toxicity (DLT) analysis population consists of stratum 1A phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (course 1 and 2) or who completed the MTD estimation period without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD based on the tradional 3+3 design, where a dose is considered a safe dose only when 0 out of 3, or at most 1 out of 6 patients has DLTs. When two or more patients in a group of 2 to 6 patients had DLTs, then that dose level was considered to be too toxic.
Median Progression-free Survival in Newly Diagnosed Brain Stem Gliomas
时间窗: Assessed pre-radiation, every 8 weeks for 13 courses of therapy, and then every 12 weeks
Progression-free survival is defined as the interval from intiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurlogical status) or death for patients who failed or to the last date of follow-up for patients without failure
Median Survival in Newly Diagnosed Brain Stem Gliomas
时间窗: Assessed from the start of therapy until three years after initiation of gefitinib therapy
Overall survival is defined as the interval from initiation of treatment to death or date of last contact for surviving patients
次要结局
- Time of Maximum Clearance of Gefitinib (Tmax)(Week 2 of course 1)
- Change From Baseline in Volume Enhancing at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Change in Tumor Volume Measured on Fluid Attenuated Inversion Recovery (FLAIR) Imaging at Before the Protocol Therapy Started and at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Mean Tumor to Gray Matter Ratio Measured at Baseline(Baseline)
- Mean Tumor to White Matter Ratio Measured at Baseline(Baseline)
- Peak Serum Concentration of Gefitinib (Cmax)(Week 2 of course 1)
- Elimination Half Life of Gefitinib (t1/2)(Week 2 of course 1)
- Clearance of Gefitinib (Cl)(Week 2 of course 1)
- Gefitinib Area Under the Concentration Curve From 0-24 Hours (AUC)(Week 2 of course 1)
- Number of Patients With Epidermal Growth Factor Receptor (EGFR) Amplification(Pre-treatment)