Medulloblastoma | Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System
Medulloblastoma research study
What is the primary objective of this study?
This pilot clinical trial studies the side effects and the best way to give vorinostat with isotretinoin and combination chemotherapy and to see how well they work in treating younger patients with embryonal tumors of the central nervous system. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as isotretinoin, vincristine sulfate, cisplatin, cyclophosphamide, and etoposide phosphate, 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 vorinostat with isotretinoin and combination chemotherapy may be an effective treatment for embryonal tumors of the central nervous system. A peripheral blood stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to be given so that more tumor cells are killed.
Who is eligible to participate?
Inclusion Criteria: - Patients must have a histologically confirmed, newly-diagnosed medulloblastoma (except for patients with the histology of localized (M0) desmoplastic medulloblastoma or atypical teratoid/rhabdoid tumor [ATRT]) or supratentorial primitive neuroectodermal tumor (PNET) including pineoblastomas - Patients must have not received any prior therapy other than surgery and/or steroids - Patient must have adequate pre-trial formalin-fixed, paraffin-embedded (FFPE) tumor material available for use in the biology studies and central pathology review; if snap frozen tissue is not available, the study chair must be contacted to discuss eligibility - Patient must be a suitable candidate, by institutional standards for stem cell apheresis - Lansky performance score (LPS for =< 16 years of age) >= 30 assessed within two weeks prior to registration - Absolute neutrophil count (ANC) >= 1000/ul (unsupported) - Platelets >= 100,000/ul (unsupported) - Hemoglobin >= 8 g/dL (may be supported) - Bilirubin < 1.5 times upper limit of normal for age - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age - Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73m^2 or estimated GFR (Schwartz bedside) that is > 99 ml/min/1.73m^2 - Parents/legal guardians must have the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines Exclusion Criteria: - Patients with diagnosis of atypical teratoid/rhabdoid tumor (ATRT by histology, immunohistochemistry and/or molecular analysis) and desmoplastic M0 medulloblastoma will be excluded from the study - Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would interfere with the study procedures or results - Patients receiving any other anticancer or investigational drug therapy are excluded - Patients having taken valproic acid within 2 weeks prior to initiation of treatment are excluded - Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy - Patients with a parabens allergy
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Supratentorial Embryonal Tumor, Not Otherwise Specified
Untreated Childhood Medulloblastoma
Untreated Childhood Pineoblastoma
Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Radiation:3-Dimensional Conformal Radiation TherapyUndergo conformal radiation therapy
Drug:Etoposide PhosphateGiven IV
Other:Laboratory Biomarker AnalysisCorrelative studies
Procedure:Peripheral Blood Stem Cell TransplantationUndergo PBSC
Drug:Vincristine SulfateGiven IV
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Treatment (vorinostat, isotretinoin, chemotherapy)See Detailed Description
Active, not recruiting
Start Date: February 25, 2009
Primary Outcome: Dose-limiting toxicity of proposed vorinostat as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Secondary Outcome: Response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites)
Study sponsors, principal investigator, and references
Principal Investigator: Sarah Leary
Lead Sponsor: National Cancer Institute (NCI)