Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Ependymoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: Induction Chemotherapy; Low-Risk Therapy; High-Risk Therapy; Intermediate-Risk Therapy
Intervention description: All patients will receive 4 identical cycles of induction chemotherapy including highdose (5 g/m2 or 2.5g/m2 for patients less than or equal to 31 days of age at enrollment) intravenous methotrexate and standard dose vincristine, cisplatin, and cyclophosphamide.; Induction will be followed by further conventional chemotherapy with carboplatin, cyclophosphamide, and etoposide. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).; High risk patients will also receive vinblastine with each course of induction chemotherapy. Induction will be followed by either chemotherapy with targeted intravenous topotecan and cyclophosphamide or optional craniospinal irradiation (CSI). CSI will be offered only to patients who reach 3 years of age by the end of induction only. After consolidation, all patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).; Induction will be followed by consolidation focal radiotherapy (RT) to the tumor bed. Patients less than 12 months old upon completion of induction will receive low risk chemotherapy to delay RT until the age of 12 months. After consolidation, patients will receive 6 cycles of oral maintenance chemotherapy with cyclophosphamide, topotecan, and depending on the diagnosis, either erlotinib or etoposide (VP-16).
Note: The option to receive focal proton beam irradiation was suspended 10/29/2015. Focal photon beam irradiation continues as part of the treatment plan.
Intervention MeSH terms: Cyclophosphamide; Cisplatin; Carboplatin; Methotrexate; Etoposide; Etoposide phosphate; Vincristine; Erlotinib Hydrochloride; Topotecan; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 293.0
Sex: All
Maximum age: 5 Years
Healthy volunteers: No
Keywords: untreated childhood medulloblastoma; untreated childhood supratentorial primitive neuroectodermal tumor; untreated childhood pineoblastoma; childhood atypical teratoid/rhabdoid tumor; childhood choroid plexus tumor; childhood high grade glioma; newly diagnosed childhood ependymoma

Summary:

      RATIONALE: In this study a combination of anti-cancer drugs (chemotherapy) is used to treat
      brain tumors in young children. Using chemotherapy gives the brain more time to develop
      before radiation is given. The chemotherapy in this study includes the drug methotrexate.
      This drug was an important part of the two clinical trials which resulted in the best
      survival results for children less than 3 years of age with medulloblastoma. Most patients
      treated on this trial will also receive radiation which is carefully targeted to the area of
      the tumor. This type of radiation (focal conformal or proton beam radiotherapy) may result in
      fewer problems with thinking and learning than radiation to the whole brain and spinal cord.

      PURPOSE: This clinical trial is studying how well giving combination chemotherapy together
      with radiation therapy works in treating young patients with newly diagnosed central nervous
      system tumors.
    

Eligibility criteria:

        Histologically confirmed newly diagnosed CNS tumors of any of the following :

          -  Medulloblastoma (all histologic subtypes, including medullomyoblastoma and melanotic
             medulloblastoma)

          -  Supratentorial primitive neuroectodermal tumor (PNET) (including CNS neuroblastoma or
             ganglioneuroblastoma, medulloepithelioma, and ependymoblastoma)

          -  Pineoblastoma

          -  Atypical teratoid rhabdoid tumor (ATRT)

          -  Choroid plexus carcinoma

          -  High grade glioma (including anaplastic astrocytoma, anaplastic oligodendroglioma,
             anaplastic ganglioglioma, pleomorphic xanthoastrocytoma with anaplastic features,
             high-grade astroblastoma , anaplastic pilocytic astrocytoma, malignant glioneuronal
             tumor, glioblastoma multiforme), or gliosarcoma,

          -  Ependymoma (including all ependymoma histological variants)

          -  Age < 3 years at time of diagnosis for all histological diagnosis. Medulloblastoma
             patients ≥ 3 and < 5years old at diagnosis who have non-metastatic disease with no
             more than 1cm2 of residual tumor are also eligible.

               -  Meets criteria for 1 of the following risk groups:

          -  Low-risk group:

               -  Histologically confirmed nodular desmoplastic medulloblastoma, including
                  medulloblastoma with extensive nodularity

                    -  Focal areas of anaplasia or other atypical features suggesting more
                       aggressive phenotype in a tumor otherwise considered nodular desmoplastic
                       should be treated on the intermediate-risk group, with final risk
                       stratification at the discretion of principal investigator and study
                       pathologist

               -  No evidence of CNS metastasis 7 to 28 days after surgery by MRI and cytologic
                  examination of lumbar cerebrospinal fluid (CSF)

                    -  Ventricular CSF from a shunt or Ommaya reservoir may be used to rule out M1
                       disease when lumbar puncture is medically contraindicated

                    -  Intermediate-risk group assignment when there is no other evidence of
                       metastasis and CSF sampling is not possible

               -  Gross total resection, defined as residual tumor or imaging abnormality (not
                  definitive for residual tumor) with a size of < 1 cm2 confirmed on postoperative
                  CT scan or MRI

               -  Brain stem invasion by the tumor in the absence of imaging evidence of residual
                  tumor (tumor size < 1 cm2) and otherwise meets criteria for the low-risk group,
                  the patient will be classified as low-risk

               -  Desmoplastic medulloblastoma patients who are ≥3 -<5 years of age will NOT be
                  eligible for the low risk arm of the protocol.

          -  Intermediate-risk group:

               -  Histologically confirmed nodular desmoplastic medulloblastoma with less than
                  gross total resection and no evidence of metastasis

               -  Any eligible histologic diagnosis other than desmoplastic medulloblastoma with no
                  evidence of CNS metastasis

               -  Medulloblastoma patients who are ≥3 and < 5 yrs of age irrespective of histology
                  and with no evidence of CNS metastasis

          -  High-risk group:

               -  Any eligible histologic diagnosis with evidence of CNS metastasis

               -  Patients with extraneural metastasis are eligible for treatment on the high-risk
                  group

        PATIENT CHARACTERISTICS:

          -  Lansky performance status ≥ 30 (except for posterior fossa syndrome)

          -  WBC > 2,000/mm3

          -  Platelets > 50,000/mm3 (without support)

          -  Hemoglobin > 8 g/dL (with or without support)

          -  ANC > 500/mm3

          -  Serum creatinine < 3 times upper limit of normal (ULN)

          -  ALT < 5 times ULN

          -  Total bilirubin < 3 times ULN

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  No more than 31 days since prior definitive surgery

          -  No prior radiotherapy or chemotherapy other than corticosteroid therapy