Pilot Study Assessing the Feasibility of a Surgery and Chemotherapy-Only Approach in the Upfront Therapy of Children With Wnt Positive Standard Risk Medulloblastoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 16
- 主要终点
- Progression Free Survival
研究概览
简要总结
Participants enrolling on this study will receive standard of care chemotherapy for Wnt positive medulloblastoma without the radiation therapy or the weekly chemotherapy that is given during radiation therapy.
详细描述
There will be 9 cycles of chemotherapy. There are two different kinds of cycles given. They are referred to as A and B.
Cycle A lasts for 6 weeks and Cycle B lasts for 4 weeks. B cycles are given after the completion of two A cycles.
Below are the details of the drugs and schedules for A and B cycles.
Cycle A (This cycle lasts 42 days)
- Lomustine (CCNU) is given by mouth on Day 1.
- Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15.
- Cisplatin is given directly into a vein over 8 hours on Day 1
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have classical histology posterior fossa medulloblastoma as determined by institutional neuro-pathological evaluation.
- •Sufficient pathologic material must be available for central analysis and review
- •Tumors will be deemed Wnt positive if, at the time of central analysis, there is:
- •Monosomy 6 as determined by array CGH
- •Gene transcript detection by NanoString supporting Wnt+ medulloblastoma
- •Absence of large-cell, anaplastic histology
- •Nuclear b-catenin IHC will be determined, but not required for the diagnosis
- •Absence of residual or disseminated disease as defined by the following criteria: Minimal residual disease as determined by post-operative imaging preferably performed within 48 hours of resection (and at most 28 days post-surgery), i.e. gross total resection or residual disease of <1.5cm2 on post-operative imaging.
- •No evidence of metastatic disease in the brain, spine or cerebral spinal fluid (CSF). Assessments must include MRI imaging of the brain and spine with and without contrast and a lumbar puncture for CSF cytology
- •Diagnostic imaging (pre and post contrast) must be forwarded to Dana-Farber Cancer Institute (DFCI) for central review to confirm eligibility
- •Patients must not have had any radiation therapy or chemotherapy for medulloblastoma prior to study enrollment
- •Patients must have a Lansky performance status of >/=30 for children </=10 years of age or a Karnofsky performance status of > 30 for children > 10 years of age.
- •Participants must have normal organ and marrow function as defined below:
- •Hemoglobin greater than 10 g/dL (can be transfused). Hemoglobin <10 g/dL due to operative blood loss is permitted.
- •Absolute neutrophil count > 1.0x109/L
- •Platelets > 100,000/uL (non-transfused)
- •Total bilirubin <1.5 x upper limit normal
- •SGOT (AST) or SGPT (ALT) <2.5 x upper limit normal (ULN) for age
- •Creatinine clearance or radioisotope GFR >70 ml/min/1.73m2 or normal serum creatinine for patient's age and gender
- •All females of child-bearing age must have a negative pregnancy test before being enrolled on study. All patients of child-bearing age must practice an effective method of birth control whilst undergoing chemotherapy on study.
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, lomustine, vincristine or cyclophosphamide.
排除标准
- 未提供
研究组 & 干预措施
Chemotherapy
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
干预措施: Lomustine (Drug)
Chemotherapy
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
干预措施: Vincristine (Drug)
Chemotherapy
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
干预措施: Cisplatin (Drug)
Chemotherapy
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
干预措施: Cyclophosphamide (Drug)
Chemotherapy
Chemotherapy Cycle A Lomustine (CCNU) is given by mouth on Day 1. Vincristine is given directly into a vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1, 8, and 15. Cisplatin is given directly into a vein over 8 hours on Day 1. This cycle lasts 42 days.
Chemotherapy Cycle B Cyclophosphamide is given into a vein over 1 hour on Days 1 and 2. MESNA, a drug to protect the bladder from the effects of cyclophosphamide, will be given 15 minutes before each dose of cyclophosphamide and repeated at 3 and 6 hours. Vincristine is given directly into a vein directly into the vein (IV) over one minute or using a minibag over several minutes by some institutions on Days 1 and 8.This cycle lasts 28 days
干预措施: Mesna (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: 3 years
To determine the feasibility of treating newly diagnosed children with non-metastatic, standard risk, Wnt positive medulloblastoma with a chemotherapy-only approach. Primary outcome measure of this study will be progression-free survival; the number of participants who with progression free survival.
次要结局
- Patterns of Failure(3 years)