HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors
Medulloblastoma, Central Nervous System Embryonal Tumors
About this trial
This is an interventional treatment trial for Medulloblastoma
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:
- 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.
- Platelet Count > 100,000/µL (transfusion independent)
- 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.
Sites / Locations
- Children's of AlabamaRecruiting
- Phoenix Children's Hospital
- Arkansas Children's HospitalRecruiting
- Memorial Care Health ServicesRecruiting
- Loma Linda University Medical CenterRecruiting
- Children's Hospital Los AngelesRecruiting
- Mattel Children's Hospital (UCLA)Recruiting
- UCSF Oakland BenioffRecruiting
- Children's Hospital Orange CountyRecruiting
- Children's Hospital ColoradoRecruiting
- Nemours Center for Cancer and Blood DisordersRecruiting
- Children's National Medical CenterRecruiting
- Shands Children's Hospital/ University of FLRecruiting
- Nemours Center for Cancer and Blood DisordersRecruiting
- Nicklaus Children's HospitalRecruiting
- Orlando HealthRecruiting
- John's Hopkins All Children's HospitalRecruiting
- Children's Healthcare of AtlantaRecruiting
- Riley Children's Hospital/University of IndianaRecruiting
- University of Iowa Hospital and ClinicsRecruiting
- University of Louisville School of MedicineRecruiting
- John's Hopkins University School of MedicineRecruiting
- Dana Farber Cancer InstituteRecruiting
- University of MichiganRecruiting
- Central Michigan UniversityRecruiting
- Helen DeVos Children's HospitalRecruiting
- Children's Hospital of MinnesotaRecruiting
- Masonic Children's Hospital/University of MinnesotaRecruiting
- Mayo ClinicRecruiting
- Washington University School of MedicineRecruiting
- Children's Specialty Care of NevadaRecruiting
- Joseph Sanzari Children's Hospital/ Hackensack UniversityRecruiting
- Morristown Medical Center, Atlantic Health System
- Northwell HealthRecruiting
- NYU Langone Medical CenterRecruiting
- Columbia Presbyterian Children's HospitalRecruiting
- Memorial Sloan Kettering Cancer Center
- Upstate Golisano Children's Hospital/ SUNY Upstate Medical UniversityRecruiting
- New York Medical CollegeRecruiting
- Carolina's HealthCare System/Levine Cancer InstituteRecruiting
- Duke University Medical CenterRecruiting
- Akron Children's Hospital
- Rainbow Babies & Children's HospitalRecruiting
- Cleveland Clinic
- Nationwide Children's HospitalRecruiting
- Dayton Children's HospitalRecruiting
- Penn State Hershey Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Medical University of South CarolinaRecruiting
- Vanderbilt-Ingram Cancer CenterRecruiting
- MD Anderson Cancer CenterRecruiting
- Primary Children's HospitalRecruiting
- Virginia Commonwealth UniversityRecruiting
- American Family Children's Hospital/University of WisconsinRecruiting
- Medical College of WisconsinRecruiting
- B.C. Children's HospitalRecruiting
- Alberta Children's HospitalRecruiting
- Stollery Children's HospitalRecruiting
- Hamilton Health/McMasters Children's Hospital, Hamilton, Canada
- The Hospital of Sick ChildrenRecruiting
- Starship Children's HospitalRecruiting
- Christchurch Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Induction
Single Cycle Intensive Chemotherapy
Tandem 3 Cycle Intensive Chemotherapy
The 5 chemotherapy drugs used in the Induction part of treatment are vincristine, cisplatin, cyclophosphamide, etoposide and high-dose methotrexate. Three medications are also given to help reduce the side effects of the chemotherapy drugs. Filgrastim will be given through a vein or through a tiny needle into the tissue just under the skin to help blood counts recover after the chemotherapy. Mesna will be given through a vein with cyclophosphamide to help prevent bleeding in the bladder. Leucovorin will be given through a vein after the methotrexate to protect the body from the side effects of the methotrexate.
The three drugs to be used in this research study are thiotepa, etoposide and carboplatin. These drugs will be given over 6 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Carboplatin is given by vein over 4 hours. Thiotepa is given by vein over 3 hours. Etoposide is given by vein over 3 hours. The schedule for these drugs is as follows: Day -8: Carboplatin Day -7: Carboplatin Day -6: Carboplatin Day -5: Thiotepa, Etoposide Day -4: Thiotepa, Etoposide Day -3: Thiotepa, Etoposide Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells
The 2 drugs to be used in this treatment are thiotepa and carboplatin. These drugs will be given over 2 days to help kill the cancer cells. After 72 hours from getting these drugs, previously collected and frozen blood cells will be thawed and returned through the venous catheter. Day -4: Thiotepa, Carboplatin Day -3: Thiotepa, Carboplatin Day -2: Rest Day -1: Rest Day 0: Re-infusion of blood cells. Following recovery from the first cycle of this chemotherapy, about 28 days following the Day 0 reinfusion of blood cells, the same cycle will be repeated again. A total of 3 cycles of this therapy will be administered, over the course of 12 weeks.