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

Status: Recruiting
Phase:
DFCI Protocol ID: 17-752

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.

Conducting Institutions:

Massachusetts General Hospital, Dana-Farber Cancer Institute, Children's Hospital Boston

Overall PI:

David Ebb, MD, Massachusetts General Hospital

Site-responsible Investigators:

Susan Chi, MD, Dana-Farber Cancer Institute

Contacts:

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

Eligibility Criteria

Inclusion Criteria:

  -  Patients must be newly diagnosed and have a confirmed molecular diagnosis of classical
     histologic type (non large cell/anaplastic [LC/A]) WNT medulloblastoma from rapid
     central pathology screening review on APEC14B1 (immunohistochemistry [IHC]/molecular
     screening [positive nuclear beta (B)-catenin by IHC and positive for catenin beta 1
     [CTNNB1] mutation) and confirmation of =< 1.5 cm^2 maximal cross-sectional area of
     residual tumor from rapid central imaging review

  -  Patient must have negative lumbar cerebrospinal fluid (CSF) cytology; CSF cytology for
     staging should be performed preferably 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

       -  Note: patients with positive CSF cytology obtained prior to 14 days after surgery
  may have cytology repeated to determine eligibility and final CSF status

  -  Patients must have eligibility confirmed by rapid central imaging review on APEC14B1;
     standard whole brain magnetic resonance imaging (MRI) with and without contrast
     (gadolinium) and spine MRI with contrast (gadolinium) must be performed at the
     following time points:

       -  Pre-operative to include an MRI of the brain with and without contrast (including
  post-contrast three-dimensional [3D] T1-weighted image [T1WI] and post-contrast
  fluid-attenuated inversion recovery [FLAIR])

       -  Pre-operative spinal MRI with gadolinium; post-operative staging spinal MRI may
  be obtained if pre-operative imaging is not possible or is suboptimal;
  pre-operative spine imaging is strongly preferred, due to the potential of
  post-operative sequelae, which could affect metastasis detection

       -  Post-operative brain MRI within 72 hours of surgery

  -  Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1422

       -  Patients must be enrolled within 36 days of definitive diagnostic surgery (day 0)

    -  Note: patients must begin treatment within 36 days of definitive surgery

  -  Patients must have no previous radiotherapy or chemotherapy other than corticosteroids

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

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

  -  Hemoglobin >= 10.0 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
  females)

       -  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
  (females)

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

    -  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]) =< 110 U/L (for the
     purpose of this study, the upper limit of normal [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
  controlled

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

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

  -  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 tumor-directed therapy other than surgical
     intervention and corticosteroids

  -  Female patients who are pregnant are ineligible

  -  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

Know Your Options

Not sure which clinical trials might be right for your child? Email our clinical trials team at clinicaltrials@danafarberbostonchildrens.org.
We can help you navigate your options.

Get Clinical Trial Updates

 

Stay informed about Dana-Farber/Boston Children's research efforts, including information on new and current clinical trials. Sign up to receive our email newsletter Advances in Pediatric Hematology/Oncology.