Clinical Trials

OBJECTIVES:

       -  Collect brain tumor tissue and an accompanying blood sample from pediatric patients with brain tumors treated at Children's Oncology Group institutions.

       -  Provide a repository for long-term storage of specimens from these patients.

       -  Make these specimens available to qualified researchers to understand the biology of pediatric brain tumors.

     OUTLINE: This is a multicenter study

     Brain tumor tissue and blood specimens are collected from patients and banked for future study.

     PROJECTED ACCRUAL: An unlimited number of specimens will be collected.

OBJECTIVES: I. To utilize a standardized battery of age-appropriate neuropsychological and behavioral tests in conjunction with Children's Oncology Group (COG) Phase III clinical trials to evaluate cognitive, social, emotional, and behavioral functioning over time. II. To institute procedures to ensure a consistent, streamlined, and efficient administration of the neuropsychological/behavioral tests in a cooperative group setting in order to maximize compliance with a standardized assessment battery conducted at 3 standardized timepoints. OUTLINE: Parent and child participants complete the COG Standard Neuropsychological and Behavioral Battery testing at 9, 30, and 60 months post-diagnosis in a 1-hour session conducted by a neuropsychologist or psychologist. The Battery consists of tests of intelligence, processing speed/attention, memory, language preference, general developmental progress, attention and behavior/social/emotional function, executive function, adoptive function, and quality of life. Additionally, parents complete a parent-report questionnaire to gather information about patient's function in terms of attention, memory, executive abilities, and behavioral, social, and emotional adaption.

OBJECTIVES: Primary - Compare event-free and overall survival of pediatric patients (3 to 7 years of age) with newly diagnosed standard-risk medulloblastoma treated with standard-dose vs reduced-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with chemotherapy comprising vincristine, cisplatin, lomustine, and cyclophosphamide. - Compare event-free and overall survival of these patients (8 to 21 years of age) treated with standard-dose craniospinal radiotherapy and posterior fossa boost vs tumor bed boost radiotherapy in combination with this chemotherapy regimen. Secondary - Compare patterns of failure in patients treated with these regimens. - Compare the cognitive, auditory, and endocrinologic effects of these regimens in these patients. - Compare the audiologic and endocrinologic toxicity from these regimens in these patients. - Develop an optimal gene expression medulloblastoma outcome predictor. - Assess quality of life and functional status in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery.Patients 3 to 7 years of age are randomized to 1 of 2 chemoradiotherapy arms. Patients 8-21 years old are assigned to arm II. - Chemoradiotherapy:Patients will undergo radiotherapy on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, and 43-47 (weeks 0-6). Patients receive vincristine IV on days 8, 15, 22, 29, 36, and 43 (weeks 1-6) beginning 31 days after surgery. Patients 3 to 7 years of age are randomized to 1 of 2 radiotherapy arms (arms I and II). Patients 8-21 years old are assigned to arm II. - Radiotherapy (first randomization): - Arm I: Patients undergo reduced-dose craniospinal radiotherapy with boost. - Arm II: Patients undergo standard-dose craniospinal radiotherapy with boost. All patients are then randomized to 1 of 2 chemoradiotherapy arms (arms III and IV). - Radiotherapy boost (second randomization): - Arm III: Patients will undergo radiotherapy boost to the entire posterior fossa. - Arm IV: Patients will undergo radiotherapy boost to the tumor bed only. - Maintenance chemotherapy: Beginning 4 weeks after completion of chemoradiotherapy, patients receive 2 different regimens of maintenance chemotherapy for a total of 9 courses. Each course in regimen A is 6 weeks (42 days) in duration. Each course in regimen B is 4 weeks (28 days) in duration. - Regimen A (courses 1, 2, 4, 5, 7, and 8): Patients receive oral lomustine and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 of weeks 11, 17, 27, 33, 43, and 49. - Regimen B (courses 3, 6, and 9): Patients receive cyclophosphamide IV over 1 hour on days 1 and 2 and vincristine IV on days 1 and 8 of weeks 23, 39, and 55. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at 3-6 months after completion of radiotherapy and at 3-4 years after study entry. Neurocognitive function may also be assessed. Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PRIMARY OBJECTIVES: I. Determine if treatment of pediatric patients with newly diagnosed supratentorial primitive neuroectodermal CNS tumors or high-risk medulloblastoma with intensive induction chemotherapy comprising vincristine, etoposide, cyclophosphamide, and cisplatin in combination with high-dose methotrexate and leucovorin calcium followed by consolidation chemotherapy comprising carboplatin and thiotepa and peripheral blood stem cell rescue results in a higher complete response rate then in patients treated with the same regimen without high-dose methotrexate and leucovorin calcium. SECONDARY OBJECTIVES: I. Determine whether biologic characterization of these tumors will refine therapeutic stratification separating atypical teratoid rhabdoid tumors from primitive neuroectodermal tumors (PNETs) and possibly identifying other markers of value for stratification within the group of PNETs. II. Compare event-free survival and patterns of failure in patients treated with these regimens. III. Compare the acute, chronic, and late effects of these regimens, particularly in terms of tolerance to the same consolidation regimen after treatment with 2 different induction regimens, in these patients. IV. Compare the gastrointestinal and nutritional toxicities of these regimens in these patients. V. Compare the quality of life outcomes in patients treated with these regimens. VI. Compare the neuropsychological effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to diagnosis* (M0 medulloblastoma with ≥ 1.5 cm² residual tumor vs M1 medulloblastoma [positive lumbar CSF cytology] vs M2, M3, or M4 medulloblastoma vs supratentorial PNET [any M-stage] vs M0 medulloblastoma < 8 months without residual disease or with < 1.5 cm² radiographic measurable residual tumor vs anaplastic M0 medulloblastoma without residual disease or with < 1.5 cm² radiographic measurable residual vs classic M0 (nondesmoplastic) medulloblastoma with < 1.5 cm² radiographic measurable residual tumor). NOTE: *All diagnoses are for children < 36 months unless otherwise noted. INDUCTION THERAPY: Patients are randomized to 1 of 2 induction treatment arms. ARM I: Patients receive vincristine IV on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3; and filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive vincristine IV on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or orally every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Once methotrexate levels are in a safe range, patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Patients also receive G-CSF IV or SC beginning 24 hours after the completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. In both arms, patients with stable disease or partial response after induction therapy proceed to second-look surgery followed by consolidation therapy. Patients with a complete response after induction therapy proceed directly to consolidation therapy. CONSOLIDATION THERAPY: Beginning no more than 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 54 and continuing until blood counts recover. Patients also receive autologous peripheral blood stem cells (PBSC) IV on day 4. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Blood and tissue samples are collected at baseline for correlative studies, including gene expression profiling, biological marker analysis (i.e., cMyc, ErbB2/ErbB4), comparative genome analysis, and mutation analysis. After completion of study therapy, patients are followed up periodically for 4 years and then annually thereafter.

PRIMARY OBJECTIVES:

     l. To compare the overall survival (OS) of subjects receiving the combination of temozolomide and irinotecan with that of subjects receiving temozolomide, irinotecan, and bevacizumab for recurrent medulloblastoma (MB)/PNET of childhood.

     SECONDARY OBJECTIVES:

     I. To assess the response rate for each treatment arm. II. To determine event-free survival (EFS) for each patient compared across regimens.

     OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

     ARM I: Patients receive oral temozolomide and irinotecan hydrochloride IV over 90 minutes on days 1-5.

     ARM II: Patients receive oral temozolomide and irinotecan hydrochloride IV as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.

     In both arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

     After completion of study treatment, patients are followed up for 5 years.