Reduced Craniospinal Radiation Therapy and Chemotherapy in Treating Younger Patients With Newly Diagnosed WNT-Driven Medulloblastoma
Medulloblastoma
About this trial
This is an interventional treatment trial for Medulloblastoma
Eligibility Criteria
Inclusion Criteria:
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
- 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 post-operatively
- 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 >= 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]) =< 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 controlled
- 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 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 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
Sites / Locations
- Children's Hospital of AlabamaRecruiting
- USA Health Strada Patient Care CenterRecruiting
- Providence Alaska Medical CenterRecruiting
- Banner Children's at DesertRecruiting
- Phoenix Childrens HospitalRecruiting
- Arkansas Children's HospitalRecruiting
- Kaiser Permanente Downey Medical CenterRecruiting
- Loma Linda University Medical CenterRecruiting
- Miller Children's and Women's Hospital Long BeachRecruiting
- Children's Hospital Los AngelesRecruiting
- Cedars Sinai Medical CenterRecruiting
- Mattel Children's Hospital UCLARecruiting
- Valley Children's HospitalRecruiting
- UCSF Benioff Children's Hospital OaklandRecruiting
- Kaiser Permanente-OaklandRecruiting
- Children's Hospital of Orange CountyRecruiting
- Lucile Packard Children's Hospital Stanford UniversityRecruiting
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer CenterRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Children's Hospital ColoradoRecruiting
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical CenterRecruiting
- Connecticut Children's Medical CenterRecruiting
- Alfred I duPont Hospital for ChildrenRecruiting
- MedStar Georgetown University Hospital
- Golisano Children's Hospital of Southwest FloridaRecruiting
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's HospitalRecruiting
- Nemours Children's Clinic-JacksonvilleRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer CenterRecruiting
- Nicklaus Children's HospitalRecruiting
- AdventHealth OrlandoRecruiting
- Arnold Palmer Hospital for ChildrenRecruiting
- Nemours Children's HospitalRecruiting
- Nemours Children's Clinic - Pensacola
- Sacred Heart HospitalRecruiting
- Johns Hopkins All Children's HospitalRecruiting
- Tampa General HospitalRecruiting
- Saint Joseph's Hospital/Children's Hospital-TampaRecruiting
- Saint Mary's HospitalRecruiting
- Children's Healthcare of Atlanta - EglestonRecruiting
- Memorial Health University Medical CenterRecruiting
- Kapiolani Medical Center for Women and ChildrenRecruiting
- Saint Luke's Cancer Institute - BoiseRecruiting
- Lurie Children's Hospital-ChicagoRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer CenterRecruiting
- Loyola University Medical CenterRecruiting
- Advocate Children's Hospital-Oak LawnRecruiting
- Advocate Children's Hospital-Park RidgeRecruiting
- Saint Jude Midwest AffiliateRecruiting
- Southern Illinois University School of MedicineRecruiting
- Riley Hospital for ChildrenRecruiting
- Ascension Saint Vincent Indianapolis HospitalRecruiting
- Blank Children's HospitalRecruiting
- University of Iowa/Holden Comprehensive Cancer CenterRecruiting
- University of Kentucky/Markey Cancer CenterRecruiting
- Norton Children's HospitalRecruiting
- Children's Hospital New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Eastern Maine Medical Center
- Maine Children's Cancer ProgramRecruiting
- Johns Hopkins University/Sidney Kimmel Cancer CenterRecruiting
- Tufts Children's Hospital
- Massachusetts General Hospital Cancer CenterRecruiting
- Dana-Farber Cancer InstituteRecruiting
- UMass Memorial Medical Center - University CampusRecruiting
- C S Mott Children's HospitalRecruiting
- Children's Hospital of MichiganRecruiting
- Ascension Saint John Hospital
- Michigan State University Clinical CenterRecruiting
- Helen DeVos Children's Hospital at Spectrum HealthRecruiting
- Spectrum Health at Butterworth Campus
- Bronson Methodist HospitalRecruiting
- West Michigan Cancer Center
- Beaumont Children's Hospital-Royal OakRecruiting
- Children's Hospitals and Clinics of Minnesota - MinneapolisRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- Mayo Clinic in RochesterRecruiting
- University of Mississippi Medical CenterRecruiting
- Columbia RegionalRecruiting
- Children's Mercy Hospitals and ClinicsRecruiting
- Cardinal Glennon Children's Medical CenterRecruiting
- Washington University School of MedicineRecruiting
- Mercy Hospital Saint LouisRecruiting
- Children's Hospital and Medical Center of OmahaRecruiting
- University of Nebraska Medical CenterRecruiting
- University Medical Center of Southern NevadaRecruiting
- Sunrise Hospital and Medical CenterRecruiting
- Alliance for Childhood Diseases/Cure 4 the Kids FoundationRecruiting
- Summerlin Hospital Medical CenterRecruiting
- Renown Regional Medical CenterRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Hackensack University Medical CenterRecruiting
- Morristown Medical CenterRecruiting
- Saint Peter's University HospitalRecruiting
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University HospitalRecruiting
- Newark Beth Israel Medical CenterRecruiting
- Saint Joseph's Regional Medical CenterRecruiting
- Albany Medical CenterRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Roswell Park Cancer InstituteRecruiting
- NYU Winthrop Hospital
- The Steven and Alexandra Cohen Children's Medical Center of New YorkRecruiting
- Mount Sinai HospitalRecruiting
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- University of Rochester
- Stony Brook University Medical Center
- State University of New York Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- Mission HospitalRecruiting
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Novant Health Presbyterian Medical CenterRecruiting
- East Carolina University
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Children's Hospital Medical Center of AkronRecruiting
- Cincinnati Children's Hospital Medical CenterRecruiting
- Rainbow Babies and Childrens HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- ProMedica Toledo Hospital/Russell J Ebeid Children's HospitalRecruiting
- University of Oklahoma Health Sciences CenterRecruiting
- Legacy Emanuel Children's HospitalRecruiting
- Oregon Health and Science UniversityRecruiting
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Lehigh Valley Hospital - Muhlenberg
- Geisinger Medical CenterRecruiting
- Penn State Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Saint Christopher's Hospital for ChildrenRecruiting
- Children's Hospital of Pittsburgh of UPMCRecruiting
- Rhode Island HospitalRecruiting
- Medical University of South CarolinaRecruiting
- Prisma Health Richland HospitalRecruiting
- BI-LO Charities Children's Cancer CenterRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- T C Thompson Children's HospitalRecruiting
- East Tennessee Childrens HospitalRecruiting
- The Children's Hospital at TriStar CentennialRecruiting
- Vanderbilt University/Ingram Cancer CenterRecruiting
- Dell Children's Medical Center of Central TexasRecruiting
- Driscoll Children's HospitalRecruiting
- Medical City Dallas HospitalRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- El Paso Children's HospitalRecruiting
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer CenterRecruiting
- Covenant Children's HospitalRecruiting
- UMC Cancer Center / UMC Health SystemRecruiting
- Children's Hospital of San AntonioRecruiting
- Methodist Children's Hospital of South TexasRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- Scott and White Memorial HospitalRecruiting
- Primary Children's HospitalRecruiting
- University of Vermont and State Agricultural CollegeRecruiting
- University of Virginia Cancer CenterRecruiting
- Inova Fairfax HospitalRecruiting
- Children's Hospital of The King's DaughtersRecruiting
- Naval Medical Center - PortsmouthRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- Carilion Children'sRecruiting
- Seattle Children's HospitalRecruiting
- Providence Sacred Heart Medical Center and Children's HospitalRecruiting
- Mary Bridge Children's Hospital and Health CenterRecruiting
- Madigan Army Medical CenterRecruiting
- West Virginia University HealthcareRecruiting
- Saint Vincent Hospital Cancer Center Green BayRecruiting
- University of Wisconsin Carbone Cancer CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Children's Hospital of WisconsinRecruiting
- John Hunter Children's HospitalRecruiting
- Women's and Children's Hospital-AdelaideRecruiting
- Princess Margaret Hospital for Children
- Perth Children's HospitalRecruiting
- Alberta Children's HospitalRecruiting
- British Columbia Children's HospitalRecruiting
- CancerCare ManitobaRecruiting
- Janeway Child Health CentreRecruiting
- IWK Health CentreRecruiting
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences CentreRecruiting
- Children's Hospital
- Children's Hospital of Eastern OntarioRecruiting
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHCRecruiting
- Centre Hospitalier Universitaire Sainte-JustineRecruiting
- Jim Pattison Children's HospitalRecruiting
- Saskatoon Cancer Centre
- HIMA San Pablo Oncologic HospitalRecruiting
- King Faisal Specialist Hospital and Research Centre
Arms of the Study
Arm 1
Experimental
Treatment (reduced radiation therapy and chemotherapy)
RADIATION THERAPY: Beginning 4-5 weeks after surgery, patients undergo craniospinal radiation therapy 5 days a week for 6 weeks. MAINTENANCE THERAPY (WEEKS 1, 3, 5, and 7): Beginning 4-6 weeks after completion of radiation therapy patients receive lomustine PO on day 1, vincristine sulfate IV over 1 minute or via minibag on days 1, 8, and 15, and cisplatin IV over 6 hours on day 1. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY (WEEKS 2, 4, AND 6): Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 2, mesna IV over 15-30 minutes on days 1 and 2, and vincristine sulfate IV over 1 minute or via minibag on days 1 and 8. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI throughout the trial.