Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed, Previously Untreated, High-Risk Medulloblastoma/PNET
Condition: Anaplastic Medulloblastoma; Medulloblastoma
MeSH terms: Medulloblastoma
Intervention: Carboplatin; Cisplatin; Cyclophosphamide; Filgrastim; Isotretinoin; Laboratory Biomarker Analysis; Quality-of-Life Assessment; Radiation Therapy; Vincristine Sulfate
Intervention description: Given IV; Given IV; Given IV; Given IV or SC; Given PO; Correlative studies; Ancillary studies; Undergo radiation therapy; Given IV
Intervention MeSH terms: Vitamin A; Cyclophosphamide; Cisplatin; Carboplatin; Vincristine; Tretinoin; Isotretinoin; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 379.0
Sex: All
Minimum age: 3 Years
Maximum age: 21 Years
Healthy volunteers: No

Summary:

      This randomized 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. Drugs used in chemotherapy, 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 to kill tumor cells. 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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

               -  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

          -  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

          -  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

          -  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)

          -  CYP450 3A4 stimulators or inhibitors should be avoided or used with great caution when
             taking cyclophosphamide; aprepitant should also 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

               -  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)

          -  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