Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
Condition: Anaplastic Medulloblastoma; Medulloblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified; Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
MeSH terms: Neoplasms; Medulloblastoma; Neuroectodermal Tumors; Neuroectodermal Tumors, Primitive
Intervention: Autologous Hematopoietic Stem Cell Transplantation; Carboplatin; Cisplatin; Cyclophosphamide; Etoposide; Filgrastim; Laboratory Biomarker Analysis; Leucovorin Calcium; Methotrexate; Quality-of-Life Assessment; Thiotepa; Vincristine Sulfate
Intervention description: Undergo autologous PBSC resuce; Given IV; Given IV; Given IV; Given IV; Given IV or SC; Correlative studies; Given IV or orally; Given IV; Ancillary studies; Given IV; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cyclophosphamide; Thiotepa; Cisplatin; Carboplatin; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Podophyllotoxin; Lenograstim; Calcium; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Maximum age: 2 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial is studying two different combination chemotherapy regimens
      to compare how well they work in treating young patients with newly diagnosed supratentorial
      primitive neuroectodermal tumors or high-risk medulloblastoma when given before additional
      intense chemotherapy followed by peripheral blood stem cell rescue. It is not yet known which
      combination chemotherapy regimen is more effective when given before a peripheral stem cell
      transplant in treating supratentorial primitive neuroectodermal tumors or medulloblastoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  High-risk medulloblastoma defined by any of the following:

               -  > 1.5 cm^2 residual disease for any medulloblastoma histology, or

               -  Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis
                  of fluid collected either before definitive surgery or at least 10 days after
                  definitive surgery unless contraindicated, or

               -  Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or

               -  M4 disease

          -  Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible
             for study entry

          -  Children less than 8 months of age at the time of definitive surgery with or without
             measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible
             for study entry

          -  Patients with anaplastic medulloblastoma are eligible regardless of M-stage or
             residual tumor

          -  Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically
             measurable residual disease < 1.5 cm^2 are eligible

          -  Cranial MRI (with and without gadolinium) must be done pre-operatively;
             post-operatively, cranial MRI (with and without gadolinium) must be done, preferably
             within 48 hours of surgery; entire spinal MRI must be obtained either pre-operatively
             (with gadolinium) or post-operatively (at least 10 days following surgery) prior to
             study enrollment (with and without gadolinium); patients with MRI evidence of spinal
             disease are eligible for this study

          -  Evaluation of lumbar CSF cytology (cytospin preparation for microscopic evaluation)
             must be performed either pre-operatively or at least 10 days after definitive surgery
             unless contraindicated

          -  Patient must have a life expectancy > 8 weeks

          -  Patient must have received no prior radiation therapy or chemotherapy other than
             corticosteroids; corticosteroids are allowable for all patients

          -  Creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

          -  Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
             serum glutamic pyruvic transaminase (SGPT) (alanine transaminase [ALT]) < 2 x ULN for
             age

          -  Shortening fraction >= 27% by echocardiogram, or

          -  Ejection fraction >= 47% by radionuclide angiogram

          -  No evidence of dyspnea at rest

          -  Pulse oximetry > 94% on room air

          -  Peripheral absolute neutrophil count (ANC) > 1,000/uL

          -  Platelet count > 100,000/uL (transfusion independent)

          -  Hemoglobin greater than 8 g/dL (may have received red blood cell [RBC] transfusions
             allowed)

          -  Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate
             (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1
             micromolar (1 x 10-7 M)

          -  Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and
             nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue
             until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal
             excretion of methotrexate is inhibited by these agents

          -  Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of
             methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M)

          -  Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and
             carbamazepine) should be avoided

          -  Clinically significant drug interactions have been reported when using vincristine
             with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors
             and inducers; selected strong inhibitors of 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

          -  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