Vorinostat and Bortezomib in Treating Patients With Progressive, Recurrent Glioblastoma Multiforme
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
About this trial
This is an interventional treatment trial for Adult Giant Cell Glioblastoma
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed glioblastoma multiforme
- Gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma) allowed
- Recurrent disease
- Must have evidence of tumor progression by MRI or CT scan after radiotherapy or after the most recent antitumor therapy
Bidimensionally measurable or evaluable disease by MRI or CT scan
- Patients receiving corticosteroids must be on a fixed dose for at least 1 week prior to baseline scan
- ECOG performance status 0-2
- WBC ≥ 3,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST ≤ 3 times ULN
- Creatinine normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after the last dose of vorinostat
- Willing to provide mandatory correlative laboratory tissue samples
- Able to take oral medications
- No uncontrolled infection
- No known hypersensitivity to any of the components of vorinostat or bortezomib
- No myocardial infarction or unstable angina within the past 6 months
- No congestive heart failure requiring use of ongoing maintenance therapy or history of life-threatening ventricular arrhythmias
No concurrent uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Psychiatric illness or social situation that would limit compliance with study requirements
- No other active malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
- No comorbid systemic illness or other severe concurrent disease that, in the judgment of the investigator, would preclude study entry or significantly interfere with proper assessment of safety and toxicity of the prescribed study regimens
Not immunocompromised
- Patients known to be HIV positive are eligible provided there is no clinical evidence of an immunocompromised state
- No peripheral neuropathy ≥ grade 2
- No peripheral neuropathy with pain ≥ grade 1
- No congenital long QT syndrome
- No prolonged OTC interval (> 450 msec)
- No other concurrent anticancer therapy (other than hormonal therapy)
- At least 8 weeks since prior radiotherapy
- More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless there is a separate lesion on MRI that is not part of the prior treatment field
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
No more than 1 prior chemotherapy regimen* for progressive/recurrent disease (stratum 1)
- Patients in stratum 2 may have received any number of prior chemotherapy regimens* for progressive/recurrent disease
- More than 2 weeks since prior small molecule cell cycle inhibitors
- More than 7 days since prior valproic acid
More than 7 days since prior category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including:
- 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
- More than 4 weeks since prior bevacizumab
- No prior treatment with vorinostat or bortezomib
- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin,fosphenytoin, carbamazepine, phenobarbital, or primidone)
- No other concurrent potent CYP3A4 inducer (e.g., rifampin or St. John's wort)
- No other concurrent investigational therapy for the primary neoplasm
Sites / Locations
- Mayo Clinic in Arizona
- The Medical Center of Aurora
- Boulder Community Hospital
- Penrose-Saint Francis Healthcare
- Porter Adventist Hospital
- Exempla Saint Joseph Hospital
- Presbyterian - Saint Lukes Medical Center - Health One
- Rose Medical Center
- Colorado Cancer Research Program CCOP
- Swedish Medical Center
- Saint Mary's Hospital and Regional Medical Center
- North Colorado Medical Center
- Saint Anthony Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Saint Mary Corwin Medical Center
- North Suburban Medical Center
- Exempla Lutheran Medical Center
- Mayo Clinic in Florida
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Saint Joseph Medical Center
- Graham Hospital Association
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Memorial Hospital
- Eureka Hospital
- Illinois CancerCare-Eureka
- Galesburg Cottage Hospital
- Illinois CancerCare Galesburg
- Illinois CancerCare-Cottage
- Illinois CancerCare-Havana
- Mason District Hospital
- Hopedale Medical Complex - Hospital
- Joliet Oncology-Hematology Associates Limited
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Mcdonough District Hospital
- Garneau, Stewart C MD (UIA Investigator)
- Porubcin, Michael MD (UIA Investigator)
- Sharis, Christine M MD (UIA Investigator)
- Stoffel, Thomas J MD (UIA Investigator)
- Holy Family Medical Center
- Illinois CancerCare-Monmouth
- Bromenn Regional Medical Center
- Community Cancer Center Foundation
- Illinois CancerCare-Community Cancer Center
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Pekin Cancer Treatment Center
- Pekin Hospital
- Illinois CancerCare-Pekin
- Methodist Medical Center of Illinois
- Proctor Hospital
- Illinois CancerCare-Peoria
- Illinois Oncology Research Association CCOP
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Illinois Valley Hospital
- Illinois CancerCare-Princeton
- Perry Memorial Hospital
- Illinois CancerCare-Spring Valley
- Saint Margaret's Hospital
- Carle Cancer Center
- Carle Clinic-Urbana Main
- Saint Francis Hospital and Health Centers
- Elkhart General Hospital
- Community Howard Regional Health
- IU Health La Porte Hospital
- Franciscan Saint Anthony Health-Michigan City
- Saint Joseph Regional Medical Center-Mishawaka
- Reid Hospital and Health Care Services
- Memorial Hospital of South Bend
- South Bend Clinic
- Northern Indiana Cancer Research Consortium
- Constantinou, Costas L MD (UIA Investigator)
- Cedar Rapids Oncology Association
- Mercy Hospital
- Oncology Associates at Mercy Medical Center
- Medical Oncology and Hematology Associates-West Des Moines
- Mercy Capitol
- Iowa Methodist Medical Center
- Iowa Oncology Research Association CCOP
- Medical Oncology and Hematology Associates-Des Moines
- Medical Oncology and Hematology Associates-Laurel
- Mercy Medical Center - Des Moines
- Iowa Lutheran Hospital
- Siouxland Hematology Oncology Associates
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Hospital District Sixth of Harper County
- Bixby Medical Center
- Hickman Cancer Center
- Bronson Battle Creek
- Spectrum Health Big Rapids Hospital
- Grand Rapids Clinical Oncology Program
- Mercy Health Saint Mary's
- Spectrum Health at Butterworth Campus
- Community Cancer Center of Monroe
- Mercy Memorial Hospital
- Mercy Health Partners-Hackley Campus
- Mercy Health Mercy Campus
- Lakeland Hospital
- Munson Medical Center
- Metro Health Hospital
- Sanford Clinic North-Bemidgi
- Fairview Ridges Hospital
- Mercy Hospital
- Essentia Health Duluth Clinic CCOP
- Essentia Health Saint Mary's Medical Center
- Miller-Dwan Hospital
- Fairview-Southdale Hospital
- Lake Region Healthcare Corporation-Cancer Care
- Unity Hospital
- Hutchinson Area Health Care
- Meeker County Memorial Hospital
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Virginia Piper Cancer Institute
- Hennepin County Medical Center
- North Memorial Medical Health Center
- Mayo Clinic
- Metro-Minnesota CCOP
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Ridgeview Medical Center
- Minnesota Oncology and Hematology PA-Woodbury
- Montana Cancer Consortium CCOP
- Northern Rockies Radiation Oncology Center
- Saint Vincent Healthcare
- Hematology-Oncology Centers of the Northern Rockies PC
- Billings Clinic
- Bozeman Deaconess Cancer Center
- Bozeman Deaconess Hospital
- Saint James Community Hospital and Cancer Treatment Center
- Berdeaux, Donald MD (UIA Investigator)
- Great Falls Clinic
- Northern Montana Hospital
- Saint Peter's Community Hospital
- Glacier Oncology PLLC
- Kalispell Medical Oncology
- Kalispell Regional Medical Center
- Community Medical Hospital
- Montana Cancer Specialists
- Saint Patrick Hospital - Community Hospital
- Guardian Oncology and Center for Wellness
- Rutherford Hospital
- Bismarck Cancer Center
- Mid Dakota Clinic
- Saint Alexius Medical Center
- Sanford Bismarck Medical Center
- Sanford Clinic North-Fargo
- Sanford Medical Center-Fargo
- Altru Cancer Center
- Mary Rutan Hospital
- Toledo Clinic Cancer Centers-Bowling Green
- North Coast Cancer Care-Clyde
- Riverside Methodist Hospital
- Grant Medical Center
- Mount Carmel Health Center West
- Doctors Hospital
- Grandview Hospital
- Good Samaritan Hospital - Dayton
- Miami Valley Hospital
- Samaritan North Health Center
- Dayton CCOP
- Grady Memorial Hospital
- Hematology Oncology Center Incorporated
- Blanchard Valley Hospital
- Atrium Medical Center-Middletown Regional Hospital
- Wayne Hospital
- Kettering Medical Center
- Fairfield Medical Center
- Lima Memorial Hospital
- Marietta Memorial Hospital
- Saint Luke's Hospital
- Toledo Clinic Cancer Centers-Maumee
- Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
- Licking Memorial Hospital
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- North Coast Cancer Care
- Flower Hospital
- Mercy Hospital of Tiffin
- The Toledo Hospital/Toledo Children's Hospital
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Upper Valley Medical Center
- Fulton County Health Center
- Saint Ann's Hospital
- Clinton Memorial Hospital
- Greene Memorial Hospital
- Genesis HealthCare System
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Geisinger Medical Group
- Geisinger Wyoming Valley
- AnMed Health Hospital
- Spartanburg Regional Medical Center
- Upstate Carolina CCOP
- Rapid City Regional Hospital
- Fredericksburg Oncology Inc
- Midelfort Clinic-Clairemont Campus
- Mayo Clinic Health System Eau Claire Hospital - Luther Campus
- Agnesian Cancer Center
- Rocky Mountain Oncology
- Welch Cancer Center
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Stratum 1 (not undergoing surgery)
Stratum 2 (undergoing surgery)
Patients receive oral vorinostat (SAHA) once daily on days 1-14 and bortezomib IV on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients receive oral SAHA once daily for 2 days prior to surgery and then on the day of surgery. Patients also receive bortezomib IV on the day of surgery. After receiving the 3rd dose of SAHA, patients undergo surgery to remove the tumor. Beginning at least 7 days after surgery, patients receive SAHA and bortezomib as in stratum 1.