Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

NCT ID: NCT00731731

Last Updated: 2022-08-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

125 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-07-10

Study Completion Date

2019-11-01

Brief Summary

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This phase I/II trial studies the side effects and best dose of vorinostat when given together with temozolomide and radiation therapy and to see how well they work in treating patients with newly diagnosed glioblastoma multiforme. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with temozolomide and radiation therapy may kill more tumor cells.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of vorinostat in patients with newly diagnosed glioblastoma multiforme (GBM) and gliosarcomas, who are also receiving concomitant radiation therapy (RT) and temozolomide (TMZ). (Phase I) II. To define the safety of vorinostat with RT and TMZ in this population. (Phase II) III. To determine the efficacy of vorinostat in combination with RT and TMZ followed by vorinostat in combination with TMZ in patients with newly-diagnosed GBM and gliosarcomas as measured by overall survival at 15 months (OS15). (Phase II)

SECONDARY OBJECTIVES:

I. To determine progression-free survival in newly diagnosed GBM and gliosarcoma patients treated with the study regimen. (Phase II) II. To further evaluate the safety profile of vorinostat in combination with RT and TMZ in this patient population. (Phase II) III. Determine the neurocognitive effects in patients treated on this protocol and correlate these results with outcome endpoints. (Phase II)

TERTIARY OBJECTIVES:

I. To explore the extent to which the tumor's molecular characteristics and expression profile correlate with outcome.

II. Evaluate potential mechanisms of therapy resistance in tumor samples obtained at the time of tumor progression.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients undergo radiotherapy and receive vorinostat orally (PO) once daily (QD) on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive vorinostat PO QD on days 1-7 and 15-21 and temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months for 1 year and then every 6 months for 3 years.

Conditions

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Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma

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 (radiation therapy, vorinostat, temozolomide)

Patients undergo radiotherapy and receive vorinostat PO QD on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Patients also receive temozolomide PO QD on days 1-42. Beginning 4-6 weeks later, patients receive vorinostat PO QD on days 1-7 and 15-21 and temozolomide PO QD on days 1-5. Treatment with vorinostat and temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

3-Dimensional Conformal Radiation Therapy

Intervention Type RADIATION

Undergo radiotherapy

Cognitive Assessment

Intervention Type PROCEDURE

Ancillary studies

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Temozolomide

Intervention Type DRUG

Given PO

Vorinostat

Intervention Type DRUG

Given PO

Interventions

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3-Dimensional Conformal Radiation Therapy

Undergo radiotherapy

Intervention Type RADIATION

Cognitive Assessment

Ancillary studies

Intervention Type PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Temozolomide

Given PO

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 CCRG-81045 Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo- M & B 39831 M and B 39831 Methazolastone RP-46161 SCH 52365 Temcad Temodal Temodar Temomedac TMZ L-001079038 MSK-390 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Eligibility Criteria

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Inclusion Criteria

* PRE-REGISTRATION:
* Central pathology review submission; this review is mandatory prior to registration to confirm eligibility; it should be initiated as soon after surgery as possible
* Treatment should begin \>= 2 weeks and =\< 5 weeks following surgery
* REGISTRATION:
* Histologically confirmed glioblastoma multiforme as determined by pre-registration central pathology review; Note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible
* Measurable or evaluable disease by gadolinium magnetic resonance imaging (MRI) or contrast computed tomography (CT) scan; Note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease

* Must begin partial brain radiotherapy on the same day that vorinostat and temozolomide begin
* Karnofsky performance status of \>= 60
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* White blood cell (WBC) \>= 3,000/mm\^3
* Hemoglobin \>= 10.0 g/dL; Note: this level may be reached by transfusion
* Total bilirubin =\< 2.0 x institutional upper limit of normal (ULN)
* Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 2.0 x ULN
* Creatinine =\< 1.5 mg/dL
* Life expectancy \>= 12 weeks
* Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
* For Phase I established MTD and Phase II patients only: Willing and able to complete neurocognitive testing
* Ability to provide informed written consent
* Willing to return to Alliance or Adult Brain Tumor Consortium (ABTC) enrolling institution for follow-up
* Phase I established MTD patients and Phase II patients: Willing to provide mandatory tissue samples (slides or blocks) for research purposes
* Willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with vorinostat and temozolomide

Exclusion Criteria

* Any of the following:

* Pregnant women
* Nursing women
* Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for 12 weeks after treatment has ended
* Prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors
* Prior cranial RT
* Prior Gliadel wafers
* Known hypersensitivity to any of the components of vorinostat or other agents used in study
* Valproic acid, another histone deacetylase inhibitor, =\< 2 weeks prior to registration and during treatment
* Other active malignancy =\< 3 years prior to registration; Exception: non-melanotic skin cancer or carcinoma in situ of the cervix; Note: if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
* Uncontrolled infection
* Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; Note: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
* Co-morbid systemic illness or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with proper assessment of safety and adverse events of the prescribed regimens
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
* History of myocardial infarction or unstable angina =\< 6 months prior to registration or congestive heart failure (CHF) requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
* New York Heart Association (NYHA) \>= Class II Congestive Heart Failure
* Inability to take oral medications
* Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
* Congenital long QT syndrome
* Prolonged corrected (QTc) interval (\> 450 msec)
* Any of the following Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes =\< 7 days prior to registration

* Quinidine, procainamide, disopyramide
* Amiodarone, sotalol, ibutilide, dofetilide
* Erythromycin, clarithromycin
* Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
* Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Evanthia Galanis

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

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Mayo Clinic in Arizona

Scottsdale, Arizona, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

Mayo Clinic in Florida

Jacksonville, Florida, United States

Site Status

AdventHealth Orlando

Orlando, Florida, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Hawaii Cancer Care Inc - Waterfront Plaza

Honolulu, Hawaii, United States

Site Status

Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

Straub Clinic and Hospital

Honolulu, Hawaii, United States

Site Status

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Site Status

Kuakini Medical Center

Honolulu, Hawaii, United States

Site Status

Queen's Cancer Center - Kuakini

Honolulu, Hawaii, United States

Site Status

The Cancer Center of Hawaii-Liliha

Honolulu, Hawaii, United States

Site Status

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Site Status

Castle Medical Center

Kailua, Hawaii, United States

Site Status

Wilcox Memorial Hospital and Kauai Medical Clinic

Lihue, Hawaii, United States

Site Status

Pali Momi Medical Center

‘Aiea, Hawaii, United States

Site Status

Queen's Cancer Center - Pearlridge

‘Aiea, Hawaii, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Presence Resurrection Medical Center

Chicago, Illinois, United States

Site Status

Garneau, Stewart C MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Porubcin, Michael MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Sharis, Christine M MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Spector, David MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Stoffel, Thomas J MD (UIA Investigator)

Moline, Illinois, United States

Site Status

Trinity Medical Center

Moline, Illinois, United States

Site Status

McFarland Clinic PC - Ames

Ames, Iowa, United States

Site Status

Constantinou, Costas L MD (UIA Investigator)

Bettendorf, Iowa, United States

Site Status

Medical Oncology and Hematology Associates-West Des Moines

Clive, Iowa, United States

Site Status

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Site Status

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, United States

Site Status

Medical Oncology and Hematology Associates-Des Moines

Des Moines, Iowa, United States

Site Status

Medical Oncology and Hematology Associates-Laurel

Des Moines, Iowa, United States

Site Status

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Site Status

Iowa Lutheran Hospital

Des Moines, Iowa, United States

Site Status

Siouxland Regional Cancer Center

Sioux City, Iowa, United States

Site Status

Methodist West Hospital

West Des Moines, Iowa, United States

Site Status

Mercy Medical Center-West Lakes

West Des Moines, Iowa, United States

Site Status

Cancer Center of Kansas - Chanute

Chanute, Kansas, United States

Site Status

Cancer Center of Kansas - Dodge City

Dodge City, Kansas, United States

Site Status

Cancer Center of Kansas - El Dorado

El Dorado, Kansas, United States

Site Status

Cancer Center of Kansas - Fort Scott

Fort Scott, Kansas, United States

Site Status

Cancer Center of Kansas-Independence

Independence, Kansas, United States

Site Status

Cancer Center of Kansas-Kingman

Kingman, Kansas, United States

Site Status

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Site Status

Cancer Center of Kansas-Liberal

Liberal, Kansas, United States

Site Status

Cancer Center of Kansas - Newton

Newton, Kansas, United States

Site Status

Cancer Center of Kansas - Parsons

Parsons, Kansas, United States

Site Status

Cancer Center of Kansas - Pratt

Pratt, Kansas, United States

Site Status

Cancer Center of Kansas - Salina

Salina, Kansas, United States

Site Status

Cancer Center of Kansas - Wellington

Wellington, Kansas, United States

Site Status

Associates In Womens Health

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas-Wichita Medical Arts Tower

Wichita, Kansas, United States

Site Status

Ascension Via Christi Hospitals Wichita

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States

Site Status

Wichita NCI Community Oncology Research Program

Wichita, Kansas, United States

Site Status

Cancer Center of Kansas - Winfield

Winfield, Kansas, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

Cancer Trials Support Unit

Rockville, Maryland, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States

Site Status

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Site Status

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

Site Status

Munson Medical Center

Traverse City, Michigan, United States

Site Status

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, United States

Site Status

Fairview Ridges Hospital

Burnsville, Minnesota, United States

Site Status

Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Essentia Health Cancer Center

Duluth, Minnesota, United States

Site Status

Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status

Unity Hospital

Fridley, Minnesota, United States

Site Status

Hutchinson Area Health Care

Hutchinson, Minnesota, United States

Site Status

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, United States

Site Status

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States

Site Status

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

North Memorial Medical Health Center

Robbinsdale, Minnesota, United States

Site Status

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States

Site Status

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

United Hospital

Saint Paul, Minnesota, United States

Site Status

Saint Francis Regional Medical Center

Shakopee, Minnesota, United States

Site Status

Lakeview Hospital

Stillwater, Minnesota, United States

Site Status

Ridgeview Medical Center

Waconia, Minnesota, United States

Site Status

Rice Memorial Hospital

Willmar, Minnesota, United States

Site Status

Minnesota Oncology Hematology PA-Woodbury

Woodbury, Minnesota, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Montana Cancer Consortium NCORP

Billings, Montana, United States

Site Status

Nebraska Cancer Research Center

Lincoln, Nebraska, United States

Site Status

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Alegent Health Immanuel Medical Center

Omaha, Nebraska, United States

Site Status

Alegent Health Bergan Mercy Medical Center

Omaha, Nebraska, United States

Site Status

Alegent Health Lakeside Hospital

Omaha, Nebraska, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Site Status

Sanford Clinic North-Fargo

Fargo, North Dakota, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status

Green Bay Oncology at Saint Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status

Green Bay Oncology Limited at Saint Mary's Hospital

Green Bay, Wisconsin, United States

Site Status

Saint Vincent Hospital Cancer Center at Saint Mary's

Green Bay, Wisconsin, United States

Site Status

Countries

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United States

References

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Cerhan JH, Anderson SK, Butts AM, Porter AB, Jaeckle K, Galanis E, Brown PD. Examiner accuracy in cognitive testing in multisite brain-tumor clinical trials: an analysis from the Alliance for Clinical Trials in Oncology. Neurooncol Pract. 2019 Jul;6(4):283-288. doi: 10.1093/nop/npy048. Epub 2018 Nov 24.

Reference Type DERIVED
PMID: 31386061 (View on PubMed)

Other Identifiers

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NCI-2009-00672

Identifier Type: REGISTRY

Identifier Source: secondary_id

N0874

Identifier Type: -

Identifier Source: secondary_id

ABTC 0902

Identifier Type: -

Identifier Source: secondary_id

CDR0000609743

Identifier Type: -

Identifier Source: secondary_id

N0874

Identifier Type: OTHER

Identifier Source: secondary_id

N0874

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA025224

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00672

Identifier Type: -

Identifier Source: org_study_id

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