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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started
Principal Investigator

Description

Summary

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.

Official Title

Phase I/II Study of Vorinostat (Suberoylanilide Hydroxamic Acid [SAHA]), Temozolomide, and Radiation Therapy in Patients With Newly Diagnosed Glioblastoma

Details

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.

Keywords

Adult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Cognitive Side Effects of Cancer Therapy Temozolomide Dacarbazine Vorinostat

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • Mayo Clinic in Arizona
    Scottsdale, Arizona, 85259, United States
  • Montana Cancer Consortium NCORP
    Billings, Montana, 59102, United States
  • Billings Clinic Cancer Center
    Billings, Montana, 59101, United States
  • Rapid City Regional Hospital
    Rapid City, South Dakota, 57701, United States
  • Cancer Center of Kansas-Liberal
    Liberal, Kansas, 67905, United States
  • Cancer Center of Kansas - Dodge City
    Dodge City, Kansas, 67801, United States
  • Cancer Center of Kansas - Pratt
    Pratt, Kansas, 67124, United States
  • Cancer Center of Kansas-Kingman
    Kingman, Kansas, 67068, United States
  • Cancer Center of Kansas - Salina
    Salina, Kansas, 67401, United States
  • Cancer Center of Kansas - Newton
    Newton, Kansas, 67114, United States
  • Cancer Center of Kansas - Wellington
    Wellington, Kansas, 67152, United States
  • Cancer Center of Kansas - Wichita
    Wichita, Kansas, 67214, United States
  • Via Christi Regional Medical Center
    Wichita, Kansas, 67214, United States
  • Wichita NCI Community Oncology Research Program
    Wichita, Kansas, 67214, United States
  • Associates In Womens Health
    Wichita, Kansas, 67208, United States
  • Cancer Center of Kansas-Wichita Medical Arts Tower
    Wichita, Kansas, 67208, United States
  • Cancer Center of Kansas - Winfield
    Winfield, Kansas, 67156, United States
  • Cancer Center of Kansas - El Dorado
    El Dorado, Kansas, 67042, United States
  • Nebraska Cancer Research Center
    Lincoln, Nebraska, 68510, United States
  • Sanford USD Medical Center - Sioux Falls
    Sioux Falls, South Dakota, 57117-5134, United States
  • Siouxland Regional Cancer Center
    Sioux City, Iowa, 51101, United States
  • Alegent Health Lakeside Hospital
    Omaha, Nebraska, 68130, United States
  • Alegent Health Bergan Mercy Medical Center
    Omaha, Nebraska, 68124, United States
  • Alegent Health Immanuel Medical Center
    Omaha, Nebraska, 68122, United States
  • Missouri Valley Cancer Consortium
    Omaha, Nebraska, 68106, United States
  • Cancer Center of Kansas-Independence
    Independence, Kansas, 67301, United States
  • Cancer Center of Kansas - Chanute
    Chanute, Kansas, 66720, United States
  • Lawrence Memorial Hospital
    Lawrence, Kansas, 66044, United States
  • Cancer Center of Kansas - Parsons
    Parsons, Kansas, 67357, United States
  • Sanford Clinic North-Fargo
    Fargo, North Dakota, 58122, United States
  • Sanford Medical Center-Fargo
    Fargo, North Dakota, 58122, United States
  • Cancer Center of Kansas - Fort Scott
    Fort Scott, Kansas, 66701, United States
  • Rice Memorial Hospital
    Willmar, Minnesota, 56201, United States
  • Methodist West Hospital
    West Des Moines, Iowa, 50266-7700, United States
  • Mercy Medical Center-West Lakes
    West Des Moines, Iowa, 50266, United States
  • Medical Oncology and Hematology Associates-West Des Moines
    Clive, Iowa, 50325, United States
  • Mercy Cancer Center-West Lakes
    Clive, Iowa, 50325, United States
  • Medical Oncology and Hematology Associates-Laurel
    Des Moines, Iowa, 50314, United States
  • Mercy Medical Center - Des Moines
    Des Moines, Iowa, 50314, United States
  • Hutchinson Area Health Care
    Hutchinson, Minnesota, 55350, United States
  • Iowa Methodist Medical Center
    Des Moines, Iowa, 50309, United States
  • Iowa-Wide Oncology Research Coalition NCORP
    Des Moines, Iowa, 50309, United States
  • Medical Oncology and Hematology Associates-Des Moines
    Des Moines, Iowa, 50309, United States
  • Iowa Lutheran Hospital
    Des Moines, Iowa, 50316, United States
  • McFarland Clinic PC-William R Bliss Cancer Center
    Ames, Iowa, 50010, United States
  • Coborn Cancer Center at Saint Cloud Hospital
    Saint Cloud, Minnesota, 56303, United States
  • Ridgeview Medical Center
    Waconia, Minnesota, 55387, United States
  • Sanford Clinic North-Bemidgi
    Bemidji, Minnesota, 56601, United States
  • Saint Francis Regional Medical Center
    Shakopee, Minnesota, 55379, United States
  • Fairview-Southdale Hospital
    Edina, Minnesota, 55435, United States
  • Fairview Ridges Hospital
    Burnsville, Minnesota, 55337, United States
  • Metro Minnesota Community Oncology Research Consortium
    Saint Louis Park, Minnesota, 55416, United States
  • Park Nicollet Clinic - Saint Louis Park
    Saint Louis Park, Minnesota, 55416, United States
  • North Memorial Medical Health Center
    Robbinsdale, Minnesota, 55422, United States
  • Mercy Hospital
    Coon Rapids, Minnesota, 55433, United States
  • Abbott-Northwestern Hospital
    Minneapolis, Minnesota, 55407, United States
  • Hennepin County Medical Center
    Minneapolis, Minnesota, 55415, United States
  • Unity Hospital
    Fridley, Minnesota, 55432, United States
  • United Hospital
    Saint Paul, Minnesota, 55102, United States
  • Regions Hospital
    Saint Paul, Minnesota, 55101, United States
  • Minnesota Oncology Hematology PA-Maplewood
    Maplewood, Minnesota, 55109, United States
  • Saint John's Hospital - Healtheast
    Maplewood, Minnesota, 55109, United States
  • Minnesota Oncology Hematology PA-Woodbury
    Woodbury, Minnesota, 55125, United States
  • Lakeview Hospital
    Stillwater, Minnesota, 55082, United States
  • Mayo Clinic
    Rochester, Minnesota, 55905, United States
  • Essentia Health Cancer Center
    Duluth, Minnesota, 55805, United States
  • Garneau, Stewart C MD (UIA Investigator)
    Moline, Illinois, 61265, United States
  • Porubcin, Michael MD (UIA Investigator)
    Moline, Illinois, 61265, United States
  • Sharis, Christine M MD (UIA Investigator)
    Moline, Illinois, 61265, United States
  • Spector, David MD (UIA Investigator)
    Moline, Illinois, 61265, United States
  • Stoffel, Thomas J MD (UIA Investigator)
    Moline, Illinois, 61265, United States
  • Trinity Medical Center
    Moline, Illinois, 61265, United States
  • Constantinou, Costas L MD (UIA Investigator)
    Bettendorf, Iowa, 52722, United States
  • Green Bay Oncology Limited at Saint Mary's Hospital
    Green Bay, Wisconsin, 54303, United States
  • Saint Vincent Hospital Cancer Center at Saint Mary's
    Green Bay, Wisconsin, 54303, United States
  • Presence Resurrection Medical Center
    Chicago, Illinois, 60631, United States
  • Green Bay Oncology at Saint Vincent Hospital
    Green Bay, Wisconsin, 54301-3526, United States
  • Saint Vincent Hospital Cancer Center Green Bay
    Green Bay, Wisconsin, 54301, United States
  • Rush University Medical Center
    Chicago, Illinois, 60612, United States
  • Cancer Research Consortium of West Michigan NCORP
    Grand Rapids, Michigan, 49503, United States
  • Mercy Health Saint Mary's
    Grand Rapids, Michigan, 49503, United States
  • Spectrum Health at Butterworth Campus
    Grand Rapids, Michigan, 49503, United States
  • Munson Medical Center
    Traverse City, Michigan, 49684, United States
  • Henry Ford Hospital
    Detroit, Michigan, 48202, United States
  • Emory University/Winship Cancer Institute
    Atlanta, Georgia, 30322, United States
  • Cleveland Clinic Foundation
    Cleveland, Ohio, 44195, United States
  • University of Pittsburgh Cancer Institute (UPCI)
    Pittsburgh, Pennsylvania, 15232, United States
  • Wake Forest University Health Sciences
    Winston-Salem, North Carolina, 27157, United States
  • Mayo Clinic in Florida
    Jacksonville, Florida, 32224-9980, United States
  • University of Virginia Cancer Center
    Charlottesville, Virginia, 22908, United States
  • Florida Hospital Orlando
    Orlando, Florida, 32803, United States
  • Cancer Trials Support Unit
    Rockville, Maryland, 20850-2062, United States
  • Johns Hopkins University/Sidney Kimmel Cancer Center
    Baltimore, Maryland, 21287, United States
  • Geisinger Wyoming Valley/Henry Cancer Center
    Wilkes-Barre, Pennsylvania, 18711, United States
  • Castle Medical Center
    Kailua, Hawaii, 96734, United States
  • Hawaii Cancer Care Inc-POB II
    Honolulu, Hawaii, 96813, United States
  • Queen's Medical Center
    Honolulu, Hawaii, 96813, United States
  • Straub Clinic and Hospital
    Honolulu, Hawaii, 96813, United States
  • University of Hawaii Cancer Center
    Honolulu, Hawaii, 96813, United States
  • Hawaii Oncology Inc-Kuakini
    Honolulu, Hawaii, 96817, United States
  • Kuakini Medical Center
    Honolulu, Hawaii, 96817, United States
  • The Cancer Center of Hawaii-Liliha
    Honolulu, Hawaii, 96817, United States
  • Kapiolani Medical Center for Women and Children
    Honolulu, Hawaii, 96826, United States
  • Hawaii Oncology Inc-Pali Momi
    Aiea, Hawaii, 96701, United States
  • Pali Momi Medical Center
    Aiea, Hawaii, 96701, United States
  • University of Pennsylvania/Abramson Cancer Center
    Philadelphia, Pennsylvania, 19104, United States
  • Wilcox Memorial Hospital and Kauai Medical Clinic
    Lihue, Hawaii, 96766, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts, 02215, United States
  • Massachusetts General Hospital Cancer Center
    Boston, Massachusetts, 02114, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
National Cancer Institute (NCI)
ID
NCT00731731
Phase
Phase 1/2
Lead Scientist
Jennifer Clarke
Study Type
Interventional
Last Updated
November 1, 2016