Phase I/II Trial of R115777 and XRT in Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy
研究概览
简要总结
Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may make tumor cells more sensitive to radiation therapy. Combining tipifarnib with radiation therapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib to see how well it works when given together with radiation therapy in treating young patients with newly diagnosed brain stem glioma. (Phase I closed to accrual as of 1/19/06)
详细描述
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) of R115777 administered concurrently with radiation therapy to pediatric patients with non-disseminated, diffuse, intrinsic brainstem gliomas who are not receiving enzyme-inducing anti-convulsant drugs (EIACD).
II. To assess the efficacy of R115777 treatment in combination with radiation therapy for patients with non-disseminated, diffuse, intrinsic pontine gliomas as measured by progression-free survival and survival distributions.
SECONDARY OBJECTIVES:
I. To characterize toxicities associated with R115777 treatment in combination with and post radiation therapy.
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
- •Newly diagnosed non-disseminated intrinsic diffuse brainstem glioma
- •Karnofsky performance scale (KPS) (for > 16 yrs of age) or Lansky performance score (LPS) (for =< 16 years of age) => 50 assessed within two weeks prior to registration
- •Prior/concurrent therapy:
- •Chemo: No prior therapy allowed
- •Radiation therapy (XRT): No prior therapy allowed
- •Bone Marrow Transplant: None prior
- •Anti-convulsants: Patients receiving EIACDs will not be eligible; however, patients may switch from EIACDs to non-EIACDs and must then be on non-EIACDs for a minimum of 7 days prior to registration
- •Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
- •Absolute neutrophil count >= 1,000/mm^3
- •Platelets >= 100,000/mm^3 (transfusion independent)
- •Hemoglobin >= 8 gm/dL (transfusion independent)
- •Serum creatinine that is less than the upper limit of institutional normal for age or GFR > 70 ml/min/1.73m2
- •Bilirubin =< 1.5 time upper limit of normal for age
- •SGPT (ALT) and SGOT (AST) < 2.5 times institutional upper limit of normal
- •Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding
- •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
- •Signed informed consent according to institutional guidelines must be obtained
排除标准
- •Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
- •Patients with disseminated intrinsic diffuse brainstem glioma
- •Patients taking enzyme-inducing anticonvulsant drugs
- •Patients with known allergy to topical or systemic imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole)
- •Patients receiving any other anticancer or experimental drug therapy
- •Patients with uncontrolled infection
研究组 & 干预措施
Treatment (radiation therapy and tipifarnib)
PHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.
干预措施: radiation therapy (Radiation)
Treatment (radiation therapy and tipifarnib)
PHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.
干预措施: tipifarnib (Drug)
结局指标
主要结局
Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy
时间窗: Day 1 of tipifarnib therapy to week 8
The dose limiting toxicity (DLT) analysis population consists of phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD.
Progression-free Survival (PFS)
时间窗: Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks.
PFS was defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.
次要结局
- Change From Baseline in Diffusion Ratio 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)
- Mean Tumor to Gray Matter Ratio Measured at Baseline(Baseline)
- Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation(Baseline and two weeks post completion of radiation)
- Mean Tumor to White Matter Ratio Measured at Baseline(Baseline)