Vorinostat, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Study Purpose
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.
Recruitment Criteria
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Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
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Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
| Eligible Ages | 18 Years and Over |
| Gender | All |
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.
Trial Details
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Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT00731731 |
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Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 1/Phase 2 |
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Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
National Cancer Institute (NCI) |
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Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Evanthia Galanis |
| Principal Investigator Affiliation | Alliance for Clinical Trials in Oncology |
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Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
NIH |
| Overall Status | Completed |
| Countries | United States |
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Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma |
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).
- II. To define the safety of vorinostat with RT and TMZ in this population.
- 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).
- I. To determine progression-free survival in newly diagnosed GBM and gliosarcoma patients treated with the study regimen.
- II. To further evaluate the safety profile of vorinostat in combination with RT and TMZ in this patient population.
- III. Determine the neurocognitive effects in patients treated on this protocol and correlate these results with outcome endpoints.
- 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.
Arms
Experimental: 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.
Interventions
Radiation: - 3-Dimensional Conformal Radiation Therapy
Undergo radiotherapy
Procedure: - Cognitive Assessment
Ancillary studies
Other: - Laboratory Biomarker Analysis
Correlative studies
Drug: - Temozolomide
Given PO
Drug: - Vorinostat
Given PO
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Address
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
Status
Address
UCSF Medical Center-Parnassus
San Francisco, California, 94143
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Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
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Address
AdventHealth Orlando
Orlando, Florida, 32803
Status
Address
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Status
Address
Pali Momi Medical Center
'Aiea, Hawaii, 96701
Status
Address
Queen's Cancer Center - Pearlridge
'Aiea, Hawaii, 96701
Status
Address
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
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Address
Queen's Medical Center
Honolulu, Hawaii, 96813
Status
Address
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
Status
Address
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Status
Address
Kuakini Medical Center
Honolulu, Hawaii, 96817
Status
Address
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
Status
Address
The Cancer Center of Hawaii-Liliha
Honolulu, Hawaii, 96817
Status
Address
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Status
Address
Castle Medical Center
Kailua, Hawaii, 96734
Status
Address
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, 96766
Status
Address
Rush University Medical Center
Chicago, Illinois, 60612
Status
Address
Presence Resurrection Medical Center
Chicago, Illinois, 60631
Status
Address
Garneau, Stewart C MD (UIA Investigator)
Moline, Illinois, 61265
Status
Address
Porubcin, Michael MD (UIA Investigator)
Moline, Illinois, 61265
Status
Address
Sharis, Christine M MD (UIA Investigator)
Moline, Illinois, 61265
Status
Address
Spector, David MD (UIA Investigator)
Moline, Illinois, 61265
Status
Address
Stoffel, Thomas J MD (UIA Investigator)
Moline, Illinois, 61265
Status
Address
Trinity Medical Center
Moline, Illinois, 61265
Status
Address
McFarland Clinic PC - Ames
Ames, Iowa, 50010
Status
Address
Constantinou, Costas L MD (UIA Investigator)
Bettendorf, Iowa, 52722
Status
Address
Medical Oncology and Hematology Associates-West Des Moines
Clive, Iowa, 50325
Status
Address
Mercy Cancer Center-West Lakes
Clive, Iowa, 50325
Status
Address
Iowa Methodist Medical Center
Des Moines, Iowa, 50309
Status
Address
Iowa-Wide Oncology Research Coalition NCORP
Des Moines, Iowa, 50309
Status
Address
Medical Oncology and Hematology Associates-Des Moines
Des Moines, Iowa, 50309
Status
Address
Medical Oncology and Hematology Associates-Laurel
Des Moines, Iowa, 50314
Status
Address
Mercy Medical Center - Des Moines
Des Moines, Iowa, 50314
Status
Address
Iowa Lutheran Hospital
Des Moines, Iowa, 50316
Status
Address
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101
Status
Address
Methodist West Hospital
West Des Moines, Iowa, 50266-7700
Status
Address
Mercy Medical Center-West Lakes
West Des Moines, Iowa, 50266
Status
Address
Cancer Center of Kansas - Chanute
Chanute, Kansas, 66720
Status
Address
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, 67801
Status
Address
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, 67042
Status
Address
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, 66701
Status
Address
Cancer Center of Kansas-Independence
Independence, Kansas, 67301
Status
Address
Cancer Center of Kansas-Kingman
Kingman, Kansas, 67068
Status
Address
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Status
Address
Cancer Center of Kansas-Liberal
Liberal, Kansas, 67905
Status
Address
Cancer Center of Kansas - Newton
Newton, Kansas, 67114
Status
Address
Cancer Center of Kansas - Parsons
Parsons, Kansas, 67357
Status
Address
Cancer Center of Kansas - Pratt
Pratt, Kansas, 67124
Status
Address
Cancer Center of Kansas - Salina
Salina, Kansas, 67401
Status
Address
Cancer Center of Kansas - Wellington
Wellington, Kansas, 67152
Status
Address
Associates In Womens Health
Wichita, Kansas, 67208
Status
Address
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, 67208
Status
Address
Ascension Via Christi Hospitals Wichita
Wichita, Kansas, 67214
Status
Address
Cancer Center of Kansas - Wichita
Wichita, Kansas, 67214
Status
Address
Wichita NCI Community Oncology Research Program
Wichita, Kansas, 67214
Status
Address
Cancer Center of Kansas - Winfield
Winfield, Kansas, 67156
Status
Address
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Status
Address
Cancer Trials Support Unit
Rockville, Maryland, 20850-2062
Status
Address
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Status
Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Status
Address
Henry Ford Hospital
Detroit, Michigan, 48202
Status
Address
Cancer Research Consortium of West Michigan NCORP
Grand Rapids, Michigan, 49503
Status
Address
Mercy Health Saint Mary's
Grand Rapids, Michigan, 49503
Status
Address
Spectrum Health at Butterworth Campus
Grand Rapids, Michigan, 49503
Status
Address
Munson Medical Center
Traverse City, Michigan, 49684
Status
Address
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601
Status
Address
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Status
Address
Mercy Hospital
Coon Rapids, Minnesota, 55433
Status
Address
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Status
Address
Fairview Southdale Hospital
Edina, Minnesota, 55435
Status
Address
Unity Hospital
Fridley, Minnesota, 55432
Status
Address
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Status
Address
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Status
Address
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Status
Address
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Status
Address
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Status
Address
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Status
Address
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Status
Address
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303
Status
Address
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416
Status
Address
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Status
Address
Regions Hospital
Saint Paul, Minnesota, 55101
Status
Address
United Hospital
Saint Paul, Minnesota, 55102
Status
Address
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379
Status
Address
Lakeview Hospital
Stillwater, Minnesota, 55082
Status
Address
Ridgeview Medical Center
Waconia, Minnesota, 55387
Status
Address
Rice Memorial Hospital
Willmar, Minnesota, 56201
Status
Address
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Status
Address
Billings Clinic Cancer Center
Billings, Montana, 59101
Status
Address
Montana Cancer Consortium NCORP
Billings, Montana, 59102
Status
Address
Nebraska Cancer Research Center
Lincoln, Nebraska, 68510
Status
Address
Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Status
Address
Alegent Health Immanuel Medical Center
Omaha, Nebraska, 68122
Status
Address
Alegent Health Bergan Mercy Medical Center
Omaha, Nebraska, 68124
Status
Address
Alegent Health Lakeside Hospital
Omaha, Nebraska, 68130
Status
Address
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Status
Address
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Status
Address
Sanford Clinic North-Fargo
Fargo, North Dakota, 58122
Status
Address
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Status
Address
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Status
Address
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232
Status
Address
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre, Pennsylvania, 18711
Status
Address
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Status
Address
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Status
Address
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Status
Address
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, 54301-3526
Status
Address
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
Status
Address
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303
Status
Address
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303
