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

NCT00867178 | Completed Phase 1

• 4 other identifiers: NCI-2012-03167PBTC-026U01CA081457UM1CA081457
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Medulloblastoma; Pineoblastoma; Supratentorial Embryonal Tumor, Not Otherwise Specified

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity of proposed vorinostat

  Will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  Up to 21 days

• Feasibility in terms of completing 3 courses of induction therapy

  Simon's two-stage optimal design will be used to assess feasibility.

  Within 98 days

• Prognostic value of histopathological classification of pediatric medulloblastoma

  Will be assessed by single-nucleotide polymorphism (SNP) analysis and gene expression analysis. Loss of heterozygosity (LOH) analysis and copy number analysis (CNA) will be performed using dChip SNP software (or R bioconductor package) for the paired samples. Association of copy number (and LOH) with gene expression data will be explored. Correlation analysis (Pearson or Spearman Correlation, as appropriate) will be used to estimate the strength of association between each SNP and expression signal. The multiplicity issue will be addressed through estimating the False Discovery Rate.

  Up to 5 years

Secondary Outcomes (4)

• Response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites)

  Up to 5 years

• Progression-free survival (PFS)

  Up to 5 years

• Overall survival (OS)

  Up to 5 years

• Predictive values of biological markers in CSF, plasma and urine in the context of a feasibility study

  Up to 5 years

Study Arms (1)

Treatment (vorinostat, isotretinoin, chemotherapy)

EXPERIMENTAL

See Detailed Description

Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide Phosphate; Drug: Isotretinoin; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Thiotepa; Drug: Vincristine Sulfate; Drug: Vorinostat

Interventions

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo conformal radiation therapy

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal

Treatment (vorinostat, isotretinoin, chemotherapy)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (vorinostat, isotretinoin, chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (vorinostat, isotretinoin, chemotherapy)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (vorinostat, isotretinoin, chemotherapy)

Etoposide Phosphate DRUG

Given IV

Also known as: Etopophos

Treatment (vorinostat, isotretinoin, chemotherapy)

Isotretinoin DRUG

Given PO

Also known as: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid, 13-cRA, Absorica, Accure, Accutane, Amnesteem, cis-Retinoic Acid, Cistane, Claravis, Isotretinoinum, Isotrex, Isotrexin, Myorisan, Neovitamin A, Neovitamin A Acid, Oratane, Retinoicacid-13-cis, Ro 4-3780, Ro-4-3780, Roaccutan, Roaccutane, Roacutan, Sotret, ZENATANE

Treatment (vorinostat, isotretinoin, chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (vorinostat, isotretinoin, chemotherapy)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo PBSC

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, PERIPHERAL BLOOD STEM CELL TRANSPLANT, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (vorinostat, isotretinoin, chemotherapy)

Thiotepa DRUG

Given IV

Also known as: 1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene Thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Treatment (vorinostat, isotretinoin, chemotherapy)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (vorinostat, isotretinoin, chemotherapy)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Treatment (vorinostat, isotretinoin, chemotherapy)

Eligibility Criteria

• Age: 2 Months - 47 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (15)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

National Cancer Institute Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Pediatric Brain Tumor Consortium

Memphis, Tennessee, 38105, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Medulloblastoma; Pinealoma

Interventions

Radiotherapy, Conformal; Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Cyclophosphamide; etoposide phosphate; Isotretinoin; Peripheral Blood Stem Cell Transplantation; Thiotepa; Vincristine; Vorinostat

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Sarah E Leary

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2009
• First Posted: March 23, 2009
• Study Start: February 25, 2009
• Primary Completion: April 9, 2020
• Study Completion: December 22, 2021
• Last Updated: January 13, 2022

Record last verified: 2021-09

Locations

US (15)