Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma


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Trial ID: NCT02724579


This phase II trial studies how well reduced doses of radiation therapy to the brain and spine (craniospinal) and chemotherapy work in treating patients with newly diagnosed type of brain tumor called WNT)/Wingless (WNT)-driven medulloblastoma. Recent studies using chemotherapy and radiation therapy have been shown to be effective in treating patients with WNT-driven medulloblastoma. However, there is a concern about the late side effects of treatment, such as learning difficulties, lower amounts of hormones, or other problems in performing daily activities. Radiotherapy uses high-energy radiation from x-rays to kill cancer cells and shrink tumors. Drugs used in chemotherapy, such as cisplatin, vincristine sulfate, cyclophosphamide and lomustine, 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 reduced craniospinal radiation therapy and chemotherapy may kill tumor cells and may also reduce the late side effects of treatment.

Official Title

A Phase 2 Study of Reduced Therapy for Newly Diagnosed Average-Risk WNT-Driven Medulloblastoma Patients

Stanford Investigator(s)


Inclusion Criteria:

   - Patients must be greater than or equal to 3 years and less than 22 years of age at the
   time of enrollment

   - Patients must be newly diagnosed and have:

      - Eligibility confirmed by rapid central pathology and molecular screening review
      on APEC14B1:

         - Classical histologic type (non LC/A) WNT medulloblastoma

         - Positive nuclear beta-catenin by immunohistochemistry (IHC)

         - Positive for CTNNB1 mutation by Sanger sequencing

         - Negative for MYC and MYCN by fluorescence in situ hybridization (FISH)

   - Patient must have negative lumbar cerebrospinal fluid (CSF) cytology

      - Note: CSF cytology for staging should be performed no sooner than 14 days post
      operatively to avoid false positive CSF; ideally, CSF should be obtained between
      day 14 and day 21 to allow for final staging status before enrollment onto the
      study; patients with positive CSF cytology obtained 0 to 14 days after surgery
      should have cytology repeated to determine eligibility and final CSF status;
      patients with negative CSF cytology from lumbar puncture obtained 0 to 14 days
      after surgery do not need cytology repeated; patients with negative CSF cytology
      from lumbar puncture obtained prior to surgery do not need cytology repeated

   - Patients must have eligibility confirmed by Rapid Central Imaging Review on APEC14B1;
   patients must have =< 1.5 cm^2 maximal cross-sectional area of residual tumor; whole
   brain magnetic resonance imaging (MRI) with and without gadolinium and spine MRI with
   gadolinium must be performed

   - Patients must be enrolled, and protocol therapy must be projected to begin, no later
   than 36 days after definitive diagnostic surgery (day 0)

   - Peripheral absolute neutrophil count (ANC) >= 1000/uL

   - Platelet count >= 100,000/uL (transfusion independent)

   - Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

   - 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:

      - 3 to < 6 years of age: maximum (max) serum creatinine 0.8 mg/dL (males and

      - 6 to < 10 years of age: max serum creatinine 1 mg/dL (males and females)

      - 10 to < 13 years of age: max serum creatinine 1.2 mg/dL (males and females)

      - 13 to < 16 years of age: max serum creatinine 1.5 md/dL (males) and 1.4 md/dL

      - >= 16 years of age: max serum creatinine 1.7 mg/dL (males) and 1.4 mg/dL

         - The threshold creatinine values were derived from the Schwartz formula for
         estimating GFR utilizing child length and stature data published by the
         Centers for Disease Control and Prevention (CDC)

   - Total or direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

   - Serum glutamate pyruvate (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (3x ULN);
   for the purpose of this study, the ULN for SGPT is 45 U/L

   - Central nervous system function defined as:

      - Patients with seizure disorder may be enrolled if on anticonvulsants and well

      - Patients must not be in status epilepticus, a coma or on assisted ventilation at
      the time of study enrollment

   - Patients must have receptive and expressive language skills in English, French, or
   Spanish to complete the QoL and neurocognitive assessments; if a patient meets these
   criteria but the parent/guardian speaks a language other than English, French, or
   Spanish, the patient may still be enrolled and tested, and the parent-report measures
   should be omitted

   - All patients and/or their parents or legal guardians must sign a written informed
   consent; assent, when appropriate, will be obtained according to institutional

   - All institutional, Food and Drug Administration (FDA), and National Cancer Institute
   (NCI) requirements for human studies must be met

Exclusion Criteria:

   - Patients with metastatic disease by either MRI evaluation (brain and spine) or lumbar
   CSF cytology are not eligible; patients who are unable to undergo a lumbar puncture
   for assessment of CSF cytology are ineligible

   - Patients must not have received any prior radiation therapy or chemotherapy
   (tumor-directed therapy) other than surgical intervention and/or corticosteroids

   - Pregnancy and Breast Feeding

      - Female patients who are pregnant are ineligible due to risks of fetal and
      teratogenic adverse events as seen in animal/human studies

      - Lactating females are not eligible unless they have agreed not to breastfeed
      their infants

      - Female patients of childbearing potential are not eligible unless a negative
      pregnancy test result has been obtained

      - Sexually active patients of reproductive potential are not eligible unless they
      have agreed to use an effective contraceptive method for the duration of their
      study participation

   - Patients with a history of moderate to profound intellectual disability (i.e.,
   intelligence quotient [Q)]=< 55) are not eligible for enrollment; PLEASE NOTE:
   Children with a prior history of attention deficit hyperactivity disorder (ADHD) or a
   specific learning disability (e.g., dyslexia) are eligible for this study. Children
   with posterior fossa syndrome (also known as cerebellar mutism) are eligible for this


other: Laboratory Biomarker Analysis

drug: Lomustine

radiation: Radiation Therapy

drug: Vincristine Sulfate

drug: Cisplatin

drug: Cyclophosphamide

drug: Vincristine

procedure: Magnetic Resonance Imaging


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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Stefania Ursu Chirita

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