HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors

Status: Recruiting
Phase:
DFCI Protocol ID: 17-708

This is a prospective randomized clinical trial, to determine whether dose-intensive tandem Consolidation, in a randomized comparison with single cycle Consolidation, provides an event-free survival (EFS) and overall survival (OS). The study population will be high-risk patients (non-Wnt and non-Shh sub-groups) with medulloblastoma, and for all patients with central nervous system (CNS) embryonal tumors completing "Head Start 4" Induction. This study will further determine whether the additional labor intensity (duration of hospitalizations and short-term and long-term morbidities) associated with the tandem treatment is justified by the improvement in outcome. It is expected that the tandem (3 cycles) Consolidation regimen will produce a superior outcome compared to the single cycle Consolidation, given the substantially higher dose intensity of the tandem regimen, without significant addition of either short-term or long-term morbidities.

Conducting Institutions:

Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

Susan Chi, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:

Contacts:

Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Patients 10 years of age at the time of definitive confirmatory eligible histologic or
     cytologic diagnosis of eligible CNS tumor (brain or spinal cord)

  -  Patients may not have received irradiation or chemotherapy (except corticosteroids)

  -  Have histologically proven diagnosis of medulloblastoma or 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 (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

  -  CNS Embryonal Tumors:

     - Pineoblastoma, 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.

  -  Must commence Induction chemotherapy within 28 days of the most recent definitive
     surgical procedure and within 21 days of the most recent neuro-imaging studies (MRI of
     brain, performed with and without gadolinium contrast, and MRI of total spine,
     performed with gadolinium contrast) and lumbar CSF cytological examination

  -  Patients must have adequate organ functions at the time of registration:

       -  Liver: bilirubin less than 1.5 mg/dL (except for patients with Gilbert's Syndrome
  of indirect hyperbilirubinemia) and transaminases [SGPT or ALT, and SGOT or AST]
  less than 2.5 (two and a half) times the upper limits of institutional normal.

       -  Renal: Creatinine clearance and/or glomerular filtration rate (GFR) greater than
  or equal to 60 mL/min/1.73m² within 21 days of protocol therapy.

       -  Bone Marrow Function:

    1. Peripheral absolute phagocyte count (APC) > 1000/ µL. 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.

    2. Platelet Count > 100,000/µL (transfusion independent)

    3. Hemoglobin > 8 gm/dL (may have received RBC transfusions).

Exclusion Criteria:

  -  Patients older than 10 years of age at time of diagnosis

  -  Following diagnoses are not eligible for study enrollment: 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.

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