Standard Chemotherapy in Treating Young Patients with Medulloblastoma or Other Central Nervous System Embryonal Tumors
Standard Chemotherapy in Treating Young Patients with Medulloblastoma or Other Central Nervous System Embryonal Tumors
This phase IV trial studies how well standard chemotherapy works in treating young patients with medulloblastoma or other central nervous system embryonal tumors. Drugs used in standard chemotherapy 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.
Neuroblastoma (Pediatrics)
Phase IV
Children
Chemotherapy - cytotoxic,
Radiotherapy,
Supportive Care,
Therapy (NOS)
Carboplatin,
Cisplatin,
Cyclophosphamide (CTX),
Etoposide,
Filgrastim (GCSF),
Leucovorin,
Mesna,
Methotrexate,
Radiation,
Vincristine
Esbenshade, Adam
National
Vanderbilt University
06-26-2018
Eligibility
0 Years
BOTH
NO
Inclusion Criteria:
Children less than 120 months (10 years) of age at the time of definitive confirmatory eligible histologic or cytological diagnosis of eligible CNS tumor within the brain or spinal cord, who have not previously received either irradiation or chemotherapy (except corticosteroids) will be eligible for study entry
Children who have histologically proven diagnoses of the following types of CNS tumor are eligible for entry onto this protocol; the exclusive focus is on medulloblastoma and other CNS embryonal tumors of the brain or spinal cord
Medulloblastoma: * Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (formalin-fixed, parrafin-embedded [FFPE] or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis * Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis * Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
All children less than 120 months (10 years) of age, irrespective of clinical stage, with a diagnosis of any of the following CNS embryonal are eligible: pineoblastoma, pineal anlage tumor, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes [ETANTR]), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified
Histologic diagnosis is mandatory for all patients prior to study entry; study eligibility will be based on institutional pathology; however, performance (and ultimate submission for Central Pathology review) of immunohistochemically (IHC) stained slides for INI11 (to rule out CNS AT/RT), GFAP, EMA, neuronal markers (synaptophysin) for all tumors, as well as a reticulin stain for medulloblastomas displaying any degree of desmoplasia on conventional microscopy, is required; in addition, requested, but not required, are IHC slides for P53 and MIB-1/Ki-67 for all tumors
Children must be enrolled on study within 28 days of the most recent definitive tumor biopsy/resection surgical procedure and within 21 days of the most recent neuro-imaging studies (magnetic resonance imaging [MRI] of brain, performed with and without gadolinium contrast, and MRI of total spine, performed with gadolinium contrast) and lumbar CSF cytological examination; if a lumbar puncture (LP) is medically contraindicated, please contact the study chair for waiver of LP for eligibility and additional guidance; please note, day 1 begins the day after surgery and/or scans; example: Patient had tumor resection surgery on June 1, 2017, therefore the last day the patient could be enrolled is June 29, 2017 (28 days from surgery); the date protocol therapy is projected to start must be no later than 4 calendar days after the date of study enrollment
Bilirubin less than 1.5 mg/dL (except for patients with Gilberts Syndrome of indirect hyperbilirubinemia)
Transaminases (serum glutamic pyruvic transaminase [SGPT] or alanine aminotransferase [ALT], and serum glutamic oxaloacetic transaminase [SGOT] or aspartate aminotransferase [AST]) less than 2.5 (two and a half) times the upper limits of institutional normal
Creatinine clearance and/or glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m^2 within 21 days of protocol therapy; kidney function cannot be estimated by other means
Adequate Bone Marrow Function defined as: * Peripheral absolute phagocyte count (APC) > 1000/ L; APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count. * Platelet Count > 100,000/L (transfusion independent) * Hemoglobin > 8 gm/dL (may have received RBC transfusions)
Exclusion Criteria:
All diagnoses other than medulloblastoma and CNS embryonal tumors - these include: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord; all choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
Children less than 120 months (10 years) of age at the time of definitive confirmatory eligible histologic or cytological diagnosis of eligible CNS tumor within the brain or spinal cord, who have not previously received either irradiation or chemotherapy (except corticosteroids) will be eligible for study entry
Children who have histologically proven diagnoses of the following types of CNS tumor are eligible for entry onto this protocol; the exclusive focus is on medulloblastoma and other CNS embryonal tumors of the brain or spinal cord
Medulloblastoma: * Posterior fossa classic, desmoplastic or extensive nodular or anaplastic/large cell medulloblastoma with appropriate and sufficient tumor material (formalin-fixed, parrafin-embedded [FFPE] or snap frozen) for proposed assays: all stages, age less than 6 years at diagnosis * Posterior fossa classic or anaplastic/large cell medulloblastoma with sufficient tumor material (FFPE or snap frozen) for proposed assays: clinically high-stage (neuraxis or extra-neural dissemination, M1-4), age greater than 6 years to less than 10 years at diagnosis * Posterior fossa medulloblastoma, those 6 years of age and above at diagnosis, will only be eligible if they have evidence of neuraxis or extraneural dissemination. Patients 6 years of age and above with low-stage (standard-risk, M0) medulloblastoma will NOT be eligible for this study, irrespective of molecular subgroup and extend of local resection
All children less than 120 months (10 years) of age, irrespective of clinical stage, with a diagnosis of any of the following CNS embryonal are eligible: pineoblastoma, pineal anlage tumor, CNS neuroblastoma, CNS ganglioneuroblastoma, embryonal tumor with multi-layered rosettes (ETMR, including embryonal tumor with abundant neuropil and true rosettes [ETANTR]), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI1 intact) and CNS embryonal tumor, not otherwise specified
Histologic diagnosis is mandatory for all patients prior to study entry; study eligibility will be based on institutional pathology; however, performance (and ultimate submission for Central Pathology review) of immunohistochemically (IHC) stained slides for INI11 (to rule out CNS AT/RT), GFAP, EMA, neuronal markers (synaptophysin) for all tumors, as well as a reticulin stain for medulloblastomas displaying any degree of desmoplasia on conventional microscopy, is required; in addition, requested, but not required, are IHC slides for P53 and MIB-1/Ki-67 for all tumors
Children must be enrolled on study within 28 days of the most recent definitive tumor biopsy/resection surgical procedure and within 21 days of the most recent neuro-imaging studies (magnetic resonance imaging [MRI] of brain, performed with and without gadolinium contrast, and MRI of total spine, performed with gadolinium contrast) and lumbar CSF cytological examination; if a lumbar puncture (LP) is medically contraindicated, please contact the study chair for waiver of LP for eligibility and additional guidance; please note, day 1 begins the day after surgery and/or scans; example: Patient had tumor resection surgery on June 1, 2017, therefore the last day the patient could be enrolled is June 29, 2017 (28 days from surgery); the date protocol therapy is projected to start must be no later than 4 calendar days after the date of study enrollment
Bilirubin less than 1.5 mg/dL (except for patients with Gilberts Syndrome of indirect hyperbilirubinemia)
Transaminases (serum glutamic pyruvic transaminase [SGPT] or alanine aminotransferase [ALT], and serum glutamic oxaloacetic transaminase [SGOT] or aspartate aminotransferase [AST]) less than 2.5 (two and a half) times the upper limits of institutional normal
Creatinine clearance and/or glomerular filtration rate (GFR) greater than or equal to 60 mL/min/1.73m^2 within 21 days of protocol therapy; kidney function cannot be estimated by other means
Adequate Bone Marrow Function defined as: * Peripheral absolute phagocyte count (APC) > 1000/ L; APC = numbers of banded neutrophils + segmented neutrophils + metamyelocytes + monocytes + eosinophils Please note, if institution reports differential as a percentage, then APC = [percentage of banded neutrophils + segmented neutrophils+ metamyelocytes+monocytes+eosinophils] x total white cell count. * Platelet Count > 100,000/L (transfusion independent) * Hemoglobin > 8 gm/dL (may have received RBC transfusions)
Exclusion Criteria:
All diagnoses other than medulloblastoma and CNS embryonal tumors - these include: CNS atypical teratoid/rhabdoid tumor (AT/RT); all ependymomas including anaplastic ependymomas of the brain or spinal cord; all choroid plexus carcinomas; all high-grade glial and glio-neuronal tumors; all primary CNS germ cell tumors; all primary CNS sarcomas; all primary or metastatic CNS lymphomas and solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)
Patients with unbiopsied diffuse intrinsic pontine tumors will NOT be eligible for this study.
