A Study Evaluating Limited Target Volume Boost Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children With Newly Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 549
- 试验地点
- 394
- 主要终点
- Event-free Survival (EFS)
研究概览
简要总结
This randomized phase III trial is studying how well standard-dose radiation therapy works compared to reduced-dose radiation therapy in children 3-7 years of age AND how well standard volume boost radiation therapy works compared to smaller volume boost radiation therapy when given together with chemotherapy in treating young patients who have undergone surgery for newly diagnosed standard-risk medulloblastoma. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as vincristine, cisplatin, lomustine, and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving radiation therapy with chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether standard-dose radiation therapy is more effective than reduced-dose radiation therapy when given together with chemotherapy after surgery in treating young patients with medulloblastoma.
详细描述
PRIMARY OBJECTIVE:
I. To determine whether reducing the craniospinal dose of radiation therapy to 18.00 Gy in children 3-7 years of age does not compromise event-free survival and overall survival as compared to treatment with 23.40 Gy of craniospinal radiation; and to determine if reducing the irradiated volume of the primary site tumor boost from the whole posterior fossa to the tumor bed only will not compromise event-free and overall survival.
SECONDARY OBJECTIVES:
I. To evaluate patterns of failure in children treated with an irradiation boost volume smaller than conventional posterior fossa volumes.
II. To reduce the cognitive, auditory and endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of craniospinal irradiation therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed medulloblastoma located in the posterior fossa
- •Standard-risk disease
- •Minimal volume, non-disseminated disease, defined by the following:
- •Residual tumor ≤ 1.5 cm^2 confirmed by MRI with contrast imaging within 21 days after surgery
- •No metastatic disease in the head, spine, or cerebrospinal fluid (CSF) confirmed by both of the following:
- •Enhanced MRI of the spine within 5 days before surgery OR within 28 days after surgery
- •Negative cytological examination of CSF after surgery, but before study enrollment
- •Brain stem involvement allowed
- •Performance status - Karnofsky 50-100% (> 16 years of age)
- •Performance status - Lansky 30-100% (≤ 16 years of age)
- •Absolute neutrophil count > 1,500/uL
- •Platelet count > 100,000/uL (transfusion independent)
- •Hemoglobin > 10 g/dL (transfusions allowed)
- •Bilirubin < 1.5 times upper limit of normal (ULN) for age
- •AST or ALT < 1.5 times ULN for age
- •Creatinine clearance OR radioisotope glomerular filtration rate >= 70 mL/min/1.73m^2 or a serum creatinine based on age/gender as follows:
- •Age Maximum Serum Creatine (mg/dL)
- •1month to < 6 months male: 0.4 female: 0.4
- •6 months to <1 year male: 0.5 female: 0.5
- •1 year to < 2 years male: 0.6 female: 0.6
- •2 to < 6 years male: 0.8 female: 0.8
- •6 to < 10 years male: 1 female: 1
- •10 to < 13 years male: 1.2 female: 1.2
- •13 to < 16 years male: 1.5 female: 1.4
- •>= 16 years male: 1.7 female: 1.4
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No prior chemotherapy
- •Prior corticosteroids allowed
- •No prior radiotherapy
排除标准
- 未提供
研究组 & 干预措施
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Craniospinal Irradiation (Radiation)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Cisplatin (Drug)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Lomustine (Drug)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Vincristine Sulfate (Drug)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Quality-of-Life Assessment (Other)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Lomustine (Drug)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Lomustine (Drug)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Laboratory Biomarker Analysis (Other)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Craniospinal Irradiation (Radiation)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Quality-of-Life Assessment (Other)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Radiation Therapy (Radiation)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Involved-Field Radiation Therapy (Radiation)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Quality-of-Life Assessment (Other)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Craniospinal Irradiation (Radiation)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Vincristine Sulfate (Drug)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Radiation Therapy (Radiation)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Vincristine Sulfate (Drug)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Cisplatin (Drug)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Cyclophosphamide (Drug)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Cyclophosphamide (Drug)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Lomustine (Drug)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Involved-Field Radiation Therapy (Radiation)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Quality-of-Life Assessment (Other)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Cyclophosphamide (Drug)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Lomustine (Drug)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Cisplatin (Drug)
Arm VI (8-21 years of age, SDCSI, PFRT)
See Detailed Description (Arm VI)
干预措施: Vincristine Sulfate (Drug)
Arm I (3-7 years of age, LDCSI, IFRT)
See Detailed Description (Arm I)
干预措施: Cyclophosphamide (Drug)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Cisplatin (Drug)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Craniospinal Irradiation (Radiation)
Arm II (3-7 years of age, LDCSI, PFRT)
See Detailed Description (Arm II)
干预措施: Laboratory Biomarker Analysis (Other)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Craniospinal Irradiation (Radiation)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Quality-of-Life Assessment (Other)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Craniospinal Irradiation (Radiation)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Quality-of-Life Assessment (Other)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Radiation Therapy (Radiation)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Involved-Field Radiation Therapy (Radiation)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Cisplatin (Drug)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Lomustine (Drug)
Arm III (3-7 years of age, SDCSI, IFRT)
See Detailed Description (Arm III)
干预措施: Vincristine Sulfate (Drug)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Cyclophosphamide (Drug)
Arm IV (3-7 years of age, SDCSI, PFRT)
See Detailed Description (Arm IV)
干预措施: Vincristine Sulfate (Drug)
Arm V (8-21 years of age, SDCSI, IFRT)
See Detailed Description (Arm V)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Event-free Survival (EFS)
时间窗: Assessed at 3 years
EFS was defined as the time interval from date of study entry to date of disease progression, disease recurrence, second malignant neoplasm or death from any cause, whichever occurs first, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% confidence intervals (CI's).
Overall Survival (OS)
时间窗: 3 years
OS was defined as the time interval from date of study entry to date of death from any cause or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 3-year estimates are reported with 95% CI's. For purposes of this analysis, arms I, III and V (involved field radiation therapy \[IFRT\]) are combined and compared to arms II, IV and VI (posterior fossa irradiation \[PFRT\]).
次要结局
- Non-local Posterior Fossa (NLPF) Failure Rate(3 years)
- Overall Survival (OS) by Molecular Subgroup Based on Methylation Arrays(3 years)
- Progression-free Survival (PFS) by Molecular Subgroup Based on Methylation Arrays(3 years)
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 1 (4-15 Months Post Diagnosis)(4 - 15 months post diagnosis)
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)(49 - 72 months post diagnosis)
- Non-posterior Fossa (NPF) Failure Rate(3 years)
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 1 (4 - 15 Months Post Diagnosis).(4 -15 months post diagnosis)
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 2 (27 - 48 Months Post Diagnosis)(27 - 48 months post diagnosis)
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 1 (4-15 Months Post Diagnosis)(4-15 months post diagnosis)
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 2 (27-48 Months Post Diagnosis)(27-48 months post diagnosis)
- Local Posterior Fossa (LPF) Failure Rate(3 years)
- Post-treatment Grade 3+ Hearing Loss as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version (v)4(Up to 3 years)
- Compliance Rates for All Eligible and Evaluable Patients Enrolled Within Time Window 3 (49 - 72 Months Post Diagnosis)(49 - 72 months post diagnosis)
- Post-treatment Endocrine Function by CSI Group(Up to 3 years)
- Incidence of Grade 3+ Hearing Loss at 1-year Post Treatment as Assessed by CTCAE v4(Up to 3 years)
- Incidence of Endocrine Dysfunction as Measured by Growth Hormone Stimulation Tests at the Time of Completion of Therapy by Radiotherapy (RT) Group(Post-treatment up to 3 years)
- Post-treatment Neurocognitive Function as Measured by the Estimated Full-scale IQ (FSIQ) by CSI Group Within Time Window 3 (49 - 72 Months Post Diagnosis)(49 - 72 months post diagnosis)
- Post-treatment Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) by CSI Group Within Time Window 2 (27-48 Months Post Diagnosis)(27-48 months post diagnosis)