Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 379
- 试验地点
- 370
- 主要终点
- Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
研究概览
简要总结
This phase III trial studies different chemotherapy and radiation therapy regimens to compare how well they work in treating young patients with newly diagnosed, previously untreated, high-risk medulloblastoma. Chemotherapy drugs, such as vincristine sulfate, cisplatin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Radiation therapy uses high-energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Carboplatin may make tumor cells more sensitive to radiation therapy. It is not yet known which chemotherapy and radiation therapy regimen is more effective in treating brain tumors.
详细描述
PRIMARY OBJECTIVES:
I. To determine whether carboplatin radiosensitization increases long term event-free survival for high risk medulloblastoma/primitive neuroectodermal tumor (PNET) patients.
II. To determine whether isotretinoin increases long term event-free survival for high risk medulloblastoma/PNET patients.
CORRELATIVE SCIENCE OBJECTIVES:
I. To compare residual disease response to radiation alone versus radiation plus carboplatin.
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 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than or equal to 3 and less than 22 years at the time of diagnosis
- •Newly diagnosed, previously untreated: (1) M0 medulloblastoma with > 1.5 cm^2 residual; (2) M+ medulloblastoma; patients with diffusely anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor
- •As of amendment # 2, enrollment of patients with supratentorial PNET has been discontinued
- •All patients with M4 disease are not eligible
- •A pre-operative magnetic resonance imaging (MRI) scan of the brain with and without contrast is required; NOTE: computed tomography (CT) scans are NOT sufficient for study eligibility since radiation therapy planning and response will be based on MRI scans only
- •Post-operative head MRI scan with and without contrast (preferably within 72 hours post-surgery); for patients who undergo stereotactic biopsy only, either a pre or post-operative MRI is sufficient; for patients with M2 and M3 disease, a post-op MRI is strongly encouraged, but not mandatory
- •Spinal MRI imaging with and without gadolinium is required within 10 days of surgery if done pre-operatively or within 28 days of surgery if done post-operatively; for posterior fossa tumors, pre-operative MRI scans are preferred because surgically-induced inflammation/blood can be difficult to distinguish from tumor
- •Lumbar cerebrospinal fluid (CSF) cytology examination must be obtained pre-operatively or within 31 days following surgery; the optimal time for obtaining CSF is prior to surgery or 1-3 weeks following surgery; ventricular CSF (either pre- or post-op) may be used only if a post-operative spinal tap is contraindicated; if a spinal tap is contraindicated and there is no ventricular CSF available, then CSF cytology can be waived for patients with supratentorial tumors or if there is documentation of spinal subarachnoid metastases (M3); patients who are categorized as M1 must have either an intra-operative positive CSF (via lumbar puncture at the end of the procedure) or a positive lumbar CSF obtained > 7 days post-operatively (to rule out surgically induced false positives)
- •Patients must have a Karnofsky performance level of >= 30 for patients > 16 years of age or a Lansky performance scale of >= 30 for patients =< 16 years of age and life expectancy > 8 weeks
- •No previous chemotherapy or radiation therapy
- •Corticosteroids should not be used during chemotherapy administration as an antiemetic because of their effect on the blood-brain barrier
- •Clinically significant drug interactions have been reported when using vincristine with strong CYP450 3A4 inhibitors and inducers. Selected strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (cytochrome P450 3A4) include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine (vincristine sulfate)
- •The clinical outcome and significance of CYP450 interactions with cyclophosphamide are less clear. CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution; aprepitant also interacts with CYP3A4 and should be used with caution with etoposide or vincristine chemotherapy
- •Cisplatin should be used with caution with nephrotoxic drug; aminoglycoside should be avoided or used with caution during or shortly after cisplatin administration and concomitant use with amphotericin B should probably also be avoided; patients receiving cisplatin and other potentially ototoxic drugs such as aminoglycoside or loop diuretics concomitantly should be closely monitored for signs of ototoxicity
- •In patients receiving cisplatin and phenytoin or fosphenytoin, serum concentrations of phenytoin may decrease. Carbamazepine concentration may also decrease with concomitant use. Plasma levels of anticonvulsant agents should be monitored and doses adjusted during therapy with cisplatin
- •No other experimental therapy is permitted while on study
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR a serum creatinine based on age/gender as follows:
- •0.8 mg/dL (2 to < 6 years of age)
- •1.0 mg/dL (6 to < 10 years of age)
- •1.2 mg/dL (10 to < 13 years of age)
- •1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
- •1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
- •Total bilirubin < 1.5 x upper limit of normal (ULN) for age
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age; for patients on anti-seizure medications, SGOT (AST) or SGPT (ALT) must be < 5 x ULN
- •Absolute neutrophil count (ANC) >= 1,000/uL
- •Platelets >= 100,000/uL (untransfused)
- •Hemoglobin >= 8 g/dl (may be transfused)
- •There is information indicating a risk of fetal or teratogenic toxicity with this treatment. Female patients who are post-menarchal must have a negative pregnancy test; lactating female patients must agree not to breast-feed while on this trial; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- 未提供
研究组 & 干预措施
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Isotretinoin (Drug)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Vincristine Sulfate (Drug)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Quality-of-Life Assessment (Other)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Radiation Therapy (Radiation)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Cisplatin (Drug)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Lumbar Puncture (Procedure)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Radiation Therapy (Radiation)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Lumbar Puncture (Procedure)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Quality-of-Life Assessment (Other)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Radiation Therapy (Radiation)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Filgrastim (Biological)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Filgrastim (Biological)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Cisplatin (Drug)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Cyclophosphamide (Drug)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Filgrastim (Biological)
Arm A (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients undergo radiation therapy QD five days a week for 6 weeks. Patients also receive vincristine sulfate IV over 1 minute once weekly for 6 weeks. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive cisplatin IV over 6 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 8, and cyclophosphamide IV over 1 hour on days 2 and 3. Patients also receive filgrastim SC or IV beginning on day 4 and continuing until blood counts recover (at least 10 days).
Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Vincristine Sulfate (Drug)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Carboplatin (Drug)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Cyclophosphamide (Drug)
Arm B (chemoradiotherapy)
CHEMORADIOTHERAPY: Patients receive vincristine sulfate and undergo radiation therapy as in Arm A. Patients also receive carboplatin IV over 15 minutes on each day of radiation therapy. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm A.
Patients also undergo blood sample collection, lumbar puncture and MRI throughout the study.
干预措施: Vincristine Sulfate (Drug)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Cyclophosphamide (Drug)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Filgrastim (Biological)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Isotretinoin (Drug)
Arm C (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm A. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive isotretinoin PO BID on day 1 and days 16-28 and cisplatin, vincristine sulfate, cyclophosphamide, and filgrastim as in Arm A maintenance therapy. Treatment repeats every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive isotretinoin PO BID on days 15-28 every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
干预措施: Vincristine Sulfate (Drug)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Carboplatin (Drug)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Cisplatin (Drug)
Arm D (chemoradiotherapy, isotretinoin-CLOSED TO ACCRUAL)
CHEMORADIOTHERAPY: Patients undergo chemoradiotherapy as in Arm B. Six weeks after completion of chemoradiotherapy, patients proceed to maintenance therapy.
MAINTENANCE THERAPY: Patients receive maintenance therapy as in Arm C. Patients then proceed to continuation therapy.
CONTINUATION THERAPY: Patients receive continuation therapy as in Arm C.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
时间窗: Up to 5 years
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined.
Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
时间窗: Up to 5 years
The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals.
次要结局
- Tumor Response to Radiation Therapy for Patients With Medulloblastoma(12 weeks after treatment initiation)
- Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)(12 weeks after treatment initiation)
- Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma(Up to 5 years)
- Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)(Up to 5 years)
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients(6 - 12 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients(24 - 36 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients(48 - 72 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients(6 - 12 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients(24 - 36 months post diagnosis)
- The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients(48 - 72 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients(6 - 12 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for Medulloblastoma Patients(24 - 36 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for Medulloblastoma Patients(48 - 72 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients(6 - 12 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients(24 - 36 months post diagnosis)
- Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients(48 - 72 months post diagnosis)