Untreated Childhood Medulloblastoma | Vorinostat Combined With Isotretinoin and Chemotherapy in Treating Younger Patients With Embryonal Tumors of the Central Nervous System

Untreated Childhood 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) (within 14 days of registration and within 7 days of the start of treatment) - Platelets >= 100,000/ul (unsupported) (within 14 days of registration and within 7 days of the start of treatment) - Hemoglobin >= 8 g/dL (may be supported) (within 14 days of registration and within 7 days of the start of treatment) - Bilirubin < 1.5 times upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment) - Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 1.5 times institutional upper limit of normal for age (within 14 days of registration and within 7 days of the start of treatment) - Serum creatinine =< 1.5 times upper limit of institutional normal for age or glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or estimated GFR (Schwartz bedside) that is > 99 ml/min/1.73 m^2 (within 14 days of registration and within 7 days of the start of treatment) - 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?

Untreated Childhood Medulloblastoma

Untreated Childhood Pineoblastoma

Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Study Interventions

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:CarboplatinGiven IV

Drug:CisplatinGiven IV

Drug:CyclophosphamideGiven IV

Drug:Etoposide PhosphateGiven IV

Drug:IsotretinoinGiven PO

Other:Laboratory Biomarker AnalysisCorrelative studies

Procedure:Peripheral Blood Stem Cell TransplantationUndergo PBSC

Drug:ThiotepaGiven IV

Drug:Vincristine SulfateGiven IV

Drug:VorinostatGiven PO

Study Arms

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

Study Status

Active, not recruiting

Start Date: February 25, 2009

Completed Date:

Phase: Phase 1

Type: Interventional


Primary Outcome: Dose-limiting toxicity of proposed vorinostat

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 E Leary

Lead Sponsor: National Cancer Institute (NCI)


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