Combination Chemotherapy Followed By Peripheral Stem Cell Transplant in Treating Young Patients With Newly Diagnosed Supratentorial Primitive Neuroectodermal Tumors or High-Risk Medulloblastoma
Anaplastic Medulloblastoma, Medulloblastoma, Supratentorial Embryonal Tumor, Not Otherwise Specified
About this trial
This is an interventional treatment trial for Anaplastic Medulloblastoma
Eligibility Criteria
Inclusion Criteria: High-risk medulloblastoma defined by any of the following: > 1.5 cm^2 residual disease for any medulloblastoma histology, or Lumbar cerebral spinal fluid (CSF) cytology positive for tumor cells by analysis of fluid collected either before definitive surgery or at least 10 days after definitive surgery unless contraindicated, or Magnetic resonance imaging (MRI) evidence of M2 or M3 metastatic disease, or M4 disease Supratentorial primitive neuroectodermal tumor (PNET) (any M-stage) will be eligible for study entry Children less than 8 months of age at the time of definitive surgery with or without measurable radiographic residual tumor with M0 stage medulloblastoma will be eligible for study entry Patients with anaplastic medulloblastoma are eligible regardless of M-stage or residual tumor Patients with M0 classic, non-desmoplastic medulloblastoma (R1) with radiographically measurable residual disease < 1.5 cm^2 are eligible Cranial MRI (with and without gadolinium) must be done pre-operatively; post-operatively, cranial MRI (with and without gadolinium) must be done, preferably within 48 hours of surgery; entire spinal MRI must be obtained either pre-operatively (with gadolinium) or post-operatively (at least 10 days following surgery) prior to study enrollment (with and without gadolinium); patients with MRI evidence of spinal disease are eligible for this study Evaluation of lumbar CSF cytology (cytospin preparation for microscopic evaluation) must be performed either pre-operatively or at least 10 days after definitive surgery unless contraindicated Patient must have a life expectancy > 8 weeks Patient must have received no prior radiation therapy or chemotherapy other than corticosteroids; corticosteroids are allowable for all patients Creatinine clearance or radioisotope glomerular filtration rate >= 60 mL/min Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamic pyruvic transaminase (SGPT) (alanine transaminase [ALT]) < 2 x ULN for age Shortening fraction >= 27% by echocardiogram, or Ejection fraction >= 47% by radionuclide angiogram No evidence of dyspnea at rest Pulse oximetry > 94% on room air Peripheral absolute neutrophil count (ANC) > 1,000/uL Platelet count > 100,000/uL (transfusion independent) Hemoglobin greater than 8 g/dL (may have received red blood cell [RBC] transfusions allowed) Hold trimethoprim/sulfamethoxazole (Bactrim) on the day of high-dose methotrexate (HDMTX) infusion and continue to hold until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) Avoid probenecid, penicillins, cephalosporins, aspirin, proton pump inhibitors and nonsteroidal anti-inflammatory drug (NSAIDS) on the day of methotrexate and continue until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) as renal excretion of methotrexate is inhibited by these agents Avoid IV contrast media, urinary acidifiers, phenytoin, and fosphenytoin on the day of methotrexate and until the methotrexate level is less than 0.1 micromolar (1 x 10-7 M) Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine) should be avoided Clinically significant drug interactions have been reported when using vincristine with strong cytochrome P450 (CYP450) family 3 subfamily A member 4 (3A4) inhibitors and inducers; selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort; the use of these drugs should be avoided with vincristine All patients and/or their parents or legal guardians must sign a written informed consent All institutional, Food and Drug administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Sites / Locations
- Children's Hospital of Alabama
- University of Alabama at Birmingham Cancer Center
- Phoenix Childrens Hospital
- Arkansas Children's Hospital
- University of Arkansas for Medical Sciences
- Kaiser Permanente Downey Medical Center
- Loma Linda University Medical Center
- Miller Children's and Women's Hospital Long Beach
- Children's Hospital Los Angeles
- Cedars Sinai Medical Center
- Valley Children's Hospital
- Children's Hospital of Orange County
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Rady Children's Hospital - San Diego
- UCSF Medical Center-Parnassus
- Children's Hospital Colorado
- Connecticut Children's Medical Center
- Alfred I duPont Hospital for Children
- Children's National Medical Center
- Broward Health Medical Center
- Lee Memorial Health System
- Golisano Children's Hospital of Southwest Florida
- University of Florida Health Science Center - Gainesville
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
- Nemours Children's Clinic-Jacksonville
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- Nicklaus Children's Hospital
- AdventHealth Orlando
- Arnold Palmer Hospital for Children
- Nemours Children's Clinic - Orlando
- Orlando Health Cancer Institute
- Nemours Children's Hospital
- Nemours Children's Clinic - Pensacola
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Saint Mary's Hospital
- Children's Healthcare of Atlanta - Egleston
- Memorial Health University Medical Center
- University of Hawaii Cancer Center
- Saint Luke's Cancer Institute - Boise
- Lurie Children's Hospital-Chicago
- Loyola University Medical Center
- Advocate Children's Hospital-Oak Lawn
- Ascension Saint Vincent Indianapolis Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- University of Kentucky/Markey Cancer Center
- Norton Children's Hospital
- Tulane University Health Sciences Center
- Eastern Maine Medical Center
- Johns Hopkins University/Sidney Kimmel Cancer Center
- Walter Reed National Military Medical Center
- Tufts Children's Hospital
- Dana-Farber Cancer Institute
- C S Mott Children's Hospital
- Michigan State University Clinical Center
- Helen DeVos Children's Hospital at Spectrum Health
- Bronson Methodist Hospital
- Kalamazoo Center for Medical Studies
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- University of Minnesota/Masonic Cancer Center
- Mayo Clinic in Rochester
- University of Mississippi Medical Center
- Children's Mercy Hospitals and Clinics
- Cardinal Glennon Children's Medical Center
- Washington University School of Medicine
- Mercy Hospital Saint Louis
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
- Nevada Cancer Research Foundation NCORP
- Hackensack University Medical Center
- Morristown Medical Center
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
- Newark Beth Israel Medical Center
- Saint Joseph's Regional Medical Center
- Overlook Hospital
- University of New Mexico Cancer Center
- Montefiore Medical Center - Moses Campus
- Roswell Park Cancer Institute
- NYU Winthrop Hospital
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
- Memorial Sloan Kettering Cancer Center
- University of Rochester
- Stony Brook University Medical Center
- New York Medical College
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Novant Health Presbyterian Medical Center
- Sanford Broadway Medical Center
- Cincinnati Children's Hospital Medical Center
- Rainbow Babies and Childrens Hospital
- Cleveland Clinic Foundation
- Nationwide Children's Hospital
- Dayton Children's Hospital
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Mercy Children's Hospital
- University of Oklahoma Health Sciences Center
- Legacy Emanuel Children's Hospital
- Legacy Emanuel Hospital and Health Center
- Oregon Health and Science University
- Geisinger Medical Center
- Children's Hospital of Philadelphia
- Saint Christopher's Hospital for Children
- Children's Hospital of Pittsburgh of UPMC
- Medical University of South Carolina
- Prisma Health Richland Hospital
- BI-LO Charities Children's Cancer Center
- Greenville Cancer Treatment Center
- Sanford USD Medical Center - Sioux Falls
- East Tennessee Childrens Hospital
- Vanderbilt University/Ingram Cancer Center
- Texas Tech University Health Sciences Center-Amarillo
- Driscoll Children's Hospital
- Medical City Dallas Hospital
- Cook Children's Medical Center
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
- Covenant Children's Hospital
- Methodist Children's Hospital of South Texas
- University of Texas Health Science Center at San Antonio
- Primary Children's Hospital
- University of Vermont and State Agricultural College
- Inova Fairfax Hospital
- Naval Medical Center - Portsmouth
- Virginia Commonwealth University/Massey Cancer Center
- Seattle Children's Hospital
- Providence Sacred Heart Medical Center and Children's Hospital
- Mary Bridge Children's Hospital and Health Center
- Marshfield Medical Center-Marshfield
- Children's Hospital of Wisconsin
- Sydney Children's Hospital
- The Children's Hospital at Westmead
- Royal Children's Hospital
- Princess Margaret Hospital for Children
- Alberta Children's Hospital
- British Columbia Children's Hospital
- CancerCare Manitoba
- IWK Health Centre
- McMaster Children's Hospital at Hamilton Health Sciences
- Kingston Health Sciences Centre
- Children's Hospital of Eastern Ontario
- Hospital for Sick Children
- The Montreal Children's Hospital of the MUHC
- Centre Hospitalier Universitaire Sainte-Justine
- Centre Hospitalier Universitaire de Quebec
- San Jorge Children's Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Arm I (induction+consolidation chemotherapy, autologous PBSC)
Arm II (induction+consolidation chemotherapy, autologous PBSC)
Patients receive vincristine IV over 1 minute on days 1, 8, and 15; etoposide IV over 1 hour on days 1-3; cyclophosphamide IV over 1 hour on days 1 and 2; cisplatin IV over 6 hours on day 3. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
Patients receive vincristine IV over 1 minute on days 1, 8, and 15; high-dose methotrexate IV over 4 hours on day 1; and leucovorin calcium IV or PO every 6 hours beginning on day 2 and continuing until methotrexate levels are in a safe range. Patients then receive etoposide IV over 1 hour on approximately days 4, 5, and 6, cyclophosphamide IV over 1 hour on approximately days 4 and 5, and cisplatin IV over 6 hours on approximately day 6. Treatment repeats every 3 weeks for 3 courses. Within 6 weeks after completion of induction therapy, patients receive consolidation therapy comprising carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1 and 2 and G-CSF IV or SC beginning on day 5 and continuing until blood counts recover. Patients also receive autologous PBSC IV on day 4. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.