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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

33 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-25

Study Completion Date

2021-12-22

Brief Summary

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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.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To investigate the feasibility of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.

II. To describe the toxicity of administering vorinostat (SAHA) and isotretinoin for three days prior and concomitant with cisplatin based chemotherapy over three courses of induction chemotherapy.

III. To investigate prognostic values of histopathological classification and biological markers in the context of a feasibility study.

SECONDARY OBJECTIVES:

I. To estimate the preliminary response rate of this approach in patients with measurable residual disease (primary site and/or metastatic sites).

II. To estimate disease specific progression-free and overall survival, in the context of a feasibility study.

III. To explore the predictive values of biological markers in cerebrospinal fluid (CSF), plasma, urine tumor material in the context of a feasibility study.

OUTLINE:

INDUCTION THERAPY: Patients receive vorinostat orally (PO) once daily (QD) and isotretinoin PO twice daily (BID) on days 1-4; vincristine sulfate intravenously (IV) on days 4, 11, and 18; cisplatin IV over 6 hours on day 4; cyclophosphamide IV over 1 hour on days 5-6; and etoposide phosphate IV over 1 hour on days 4-6. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo peripheral blood stem cell (PBSC) harvesting after each course.

CONSOLIDATION THERAPY: Within 6 weeks (10 weeks if patient is re-staged) after completion of induction therapy, patients receive carboplatin IV over 2 hours and thiotepa IV over 2 hours on days 1-2. Patients also receive autologous PBSC rescue infusion over 6 hours on day 4. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks later, patients with M0 non-desmoplastic medulloblastoma also undergo conformal radiotherapy\* to the tumor bed.

NOTE: \*Patients with supratentorial primary tumors or metastatic disease undergo radiotherapy at the discretion of treating physician.

MAINTENANCE THERAPY: Beginning 4 weeks after completion of radiotherapy or immediately after completion of consolidation therapy, patients receive vorinostat PO QD on days 1, 3, 5, 6, 8, 10, 12, and 13 and isotretinoin PO BID on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Conditions

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Medulloblastoma Pineoblastoma Supratentorial Embryonal Tumor, Not Otherwise Specified

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (vorinostat, isotretinoin, chemotherapy)

See Detailed Description

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo conformal radiation therapy

Carboplatin

Intervention Type DRUG

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Cyclophosphamide

Intervention Type DRUG

Given IV

Etoposide Phosphate

Intervention Type DRUG

Given IV

Isotretinoin

Intervention Type DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo PBSC

Thiotepa

Intervention Type DRUG

Given IV

Vincristine Sulfate

Intervention Type DRUG

Given IV

Vorinostat

Intervention Type DRUG

Given PO

Interventions

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3-Dimensional Conformal Radiation Therapy

Undergo conformal radiation therapy

Intervention Type RADIATION

Carboplatin

Given IV

Intervention Type DRUG

Cisplatin

Given IV

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Etoposide Phosphate

Given IV

Intervention Type DRUG

Isotretinoin

Given PO

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Peripheral Blood Stem Cell Transplantation

Undergo PBSC

Intervention Type PROCEDURE

Thiotepa

Given IV

Intervention Type DRUG

Vincristine Sulfate

Given IV

Intervention Type DRUG

Vorinostat

Given PO

Intervention Type DRUG

Other Intervention Names

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3-dimensional radiation therapy 3D Conformal 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo 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 (-)-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 Etopophos 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 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 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 Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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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

Minimum Eligible Age

2 Months

Maximum Eligible Age

47 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sarah E Leary

Role: PRINCIPAL_INVESTIGATOR

Pediatric Brain Tumor Consortium

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Site Status

Children's National Medical Center

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

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

National Cancer Institute Pediatric Oncology Branch

Bethesda, Maryland, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Pediatric Brain Tumor Consortium

Memphis, Tennessee, United States

Site Status

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Countries

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United States