Know Cancer

forgot password

Phase II Study of Vorinostat (SAHA) in Combination With Bortezomib (PS-341) in Patients With Recurrent Glioblastoma Multiforme

Phase 2
18 Years
Not Enrolling
Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor

Thank you

Trial Information

Phase II Study of Vorinostat (SAHA) in Combination With Bortezomib (PS-341) in Patients With Recurrent Glioblastoma Multiforme


I. To determine the clinical efficacy of vorinostat (SAHA) and bortezomib, in terms of
progression-free survival (PFS) at 6 months, in patients with progressive, recurrent
glioblastoma multiforme.


I. To determine the clinical efficacy of this regimen, in terms of overall survival, PFS at
12 months, time to progression, and objective response rate, in these patients.

II. To identify molecular predictors of response in baseline tumor specimens from these

III. To determine molecular changes in response to this regimen in tumor specimens from
patients undergoing surgery.

OUTLINE: This is a multicenter study. Patients are stratified according to planned surgery
(no [stratum 1] vs yes [stratum 2]).

STRATUM 1 (NOT UNDERGOING SURGERY): Patients receive oral vorinostat (SAHA) once daily on
days 1-14 and bortezomib intravenously (IV) on days 1, 4, 8, and 11. Courses repeat every 21
days in the absence of disease progression or unacceptable toxicity.

STRATUM 2 (UNDERGOING SURGERY): 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

Tumor tissue samples are collected at baseline and during surgery (stratum 2) for
correlative laboratory studies. Tissue samples are analyzed for baseline total and
phosphorylated AKT and p27^KIp1 expression by IHC. Tissue samples from patients in stratum 2
are also analyzed for histone acetylation status; markers of proteasome inhibition; total
and phosphorylated Bax expression by IHC; and gene expression profiles.

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

Inclusion Criteria:

- Histologically confirmed glioblastoma multiforme

- Gliosarcoma or other grade 4 astrocytoma variant (e.g., giant cell glioblastoma)

- 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

- Ongoing or active infection

- Psychiatric illness or social situation that would limit compliance with study

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Outcome Description:

Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). The 90% confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner. Estimated and compared using Kaplan-Meier survival curves and logrank test.

Outcome Time Frame:

At 6 months

Safety Issue:


Principal Investigator

Evanthia Galanis

Investigator Role:

Principal Investigator

Investigator Affiliation:

North Central Cancer Treatment Group


United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

Related Keywords:

  • Adult Giant Cell Glioblastoma
  • Adult Glioblastoma
  • Adult Gliosarcoma
  • Recurrent Adult Brain Tumor
  • Brain Neoplasms
  • Glioblastoma
  • Gliosarcoma



Mayo Clinic Rochester, Minnesota  55905
Boulder Community Hospital Boulder, Colorado  80301-9019
Porter Adventist Hospital Denver, Colorado  80210
Rose Medical Center Denver, Colorado  80220
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
North Suburban Medical Center Thornton, Colorado  80229
Fairview Ridges Hospital Burnsville, Minnesota  55337
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Meeker County Memorial Hospital Lichfield, Minnesota  55355
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
Memorial Hospital of South Bend South Bend, Indiana  46601
Virginia Piper Cancer Institute Minneapolis, Minnesota  55407
Iowa Methodist Medical Center Des Moines, Iowa  50309
Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Great Falls Clinic Great Falls, Montana  59405
North Colorado Medical Center Greeley, Colorado  80631
McKee Medical Center Loveland, Colorado  80539
Munson Medical Center Traverse City, Michigan  49684
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Bozeman Deaconess Hospital Bozeman, Montana  59715
Kalispell Medical Oncology Kalispell, Montana  59901
Kalispell Regional Medical Center Kalispell, Montana  59901
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Welch Cancer Center Sheridan, Wyoming  82801
Elkhart General Hospital Elkhart, Indiana  46515
South Bend Clinic South Bend, Indiana  46617
Memorial Hospital Carthage, Illinois  62321
Galesburg Cottage Hospital Galesburg, Illinois  61401
Galesburg Clinic Galesburg, Illinois  61401
Mason District Hospital Havana, Illinois  62644
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Proctor Hospital Peoria, Illinois  61614
Perry Memorial Hospital Princeton, Illinois  61356
Mecosta County Medical Center Big Rapids, Michigan  49307
Community Cancer Center of Monroe Monroe, Michigan  48162
Bismarck Cancer Center Bismarck, North Dakota  58501
MeritCare Medical Group Fargo, North Dakota  58122
Wood County Oncology Center Bowling Green, Ohio  43402
Grandview Hospital Dayton, Ohio  45405
Lima Memorial Hospital Lima, Ohio  45804
Northwest Ohio Oncology Center Maumee, Ohio  43537
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Fulton County Health Center Wauseon, Ohio  43567
Exempla Lutheran Medical Center Wheat Ridge, Colorado  80033
Eureka Hospital Eureka, Illinois  61530
Mercy Hospital Coon Rapids, Minnesota  55433
Graham Hospital Association Canton, Illinois  61520
Holy Family Medical Center Des Plaines, Illinois  60016
Saint Joseph Medical Center Joliet, Illinois  60435
Pekin Hospital Pekin, Illinois  61554
Medical Oncology and Hematology Associates Des Moines, Iowa  50309
Bixby Medical Center Adrian, Michigan  49221
Fairview-Southdale Hospital Edina, Minnesota  55435
Abbott-Northwestern Hospital Minneapolis, Minnesota  55407
Regions Hospital Saint Paul, Minnesota  55101
Saint Francis Regional Medical Center Shakopee, Minnesota  55379
Altru Cancer Center Grand Forks, North Dakota  58206
Saint Luke's Hospital Maumee, Ohio  43537
Geisinger Medical Group State College, Pennsylvania  16801
Battle Creek Health System Battle Creek, Michigan  49017
Miami Valley Hospital Dayton, Ohio  45409
Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Hospital District Sixth of Harper County Anthony, Kansas  67003
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
Northern Montana Hospital Havre, Montana  59501
Mary Rutan Hospital Bellefontaine, Ohio  43311
Wayne Hospital Greenville, Ohio  45331
Clinton Memorial Hospital Wilmington, Ohio  45177
Rocky Mountain Oncology Casper, Wyoming  82609
Longmont United Hospital Longmont, Colorado  80501
Greene Memorial Hospital Xenia, Ohio  45385
Rutherford Hospital Rutherfordton, North Carolina  28139
Mayo Clinic in Arizona Scottsdale, Arizona  85259-5404
Mayo Clinic in Florida Jacksonville, Florida  32224
Metro Health Hospital Grand Rapids, Michigan  49506
Guardian Oncology and Center for Wellness Missoula, Montana  59804
LaPorte Hospital LaPorte, Indiana  46350-0250
Hennepin County Medical Center Minneapolis, Minnesota  
Toledo Clinic Oregon, Ohio  43616
Riverside Methodist Hospital Columbus, Ohio  43214
Licking Memorial Hospital Newark, Ohio  43055-2899
Mid Dakota Clinic Bismarck, North Dakota  58501
Presbyterian - Saint Lukes Medical Center - Health One Denver, Colorado  80218
Montana Cancer Consortium CCOP Billings, Montana  59101
Metro-Minnesota CCOP St. Louis Park, Minnesota  
Oncology Associates Cedar Rapids, Iowa  52403
Montana Cancer Specialists Missoula, Montana  59807-7877
Northern Indiana Cancer Research Consortium South Bend, Indiana  
OSF Saint Francis Medical Center Peoria, Illinois  61637
The Medical Center of Aurora Aurora, Colorado  80012
Penrose-Saint Francis Healthcare Colorado Springs, Colorado  80907
Saint Anthony Central Hospital Denver, Colorado  80204
Exempla Saint Joseph Hospital Denver, Colorado  80218
Colorado Cancer Research Program CCOP Denver, Colorado  80224-2522
Saint Mary's Hospital and Regional Medical Center Grand Junction, Colorado  81502
Saint Mary Corwin Medical Center Pueblo, Colorado  81004
Rush - Copley Medical Center Aurora, Illinois  60504
Hopedale Medical Complex - Hospital Hopedale, Illinois  61747
Joliet Oncology-Hematology Associates Limited Joliet, Illinois  60435
Stoffel, Thomas J MD (UIA Investigator) Moline, Illinois  61265
Garneau, Stewart C MD (UIA Investigator) Moline, Illinois  61265
Sharis, Christine M MD (UIA Investigator) Moline, Illinois  61265
Porubcin, Michael MD (UIA Investigator) Moline, Illinois  61265
Community Cancer Center Foundation Normal, Illinois  61761
Illinois CancerCare-Ottawa Clinic Ottawa, Illinois  61350
Ottawa Regional Hospital and Healthcare Center Ottawa, Illinois  61350
Pekin Cancer Treatment Center Pekin, Illinois  61554
Illinois Oncology Research Association CCOP Peoria, Illinois  61615
Illinois CancerCare-Peoria Peoria, Illinois  61615
Illinois Valley Hospital Peru, Illinois  61354
Saint Margaret's Hospital Spring Valley, Illinois  61362
Carle Foundation dba Carle Cancer Center Urbana, Illinois  61801
Carle Clinic-Urbana Main Urbana, Illinois  61801
Saint Francis Hospital and Health Centers Beech Grove, Indiana  46107
Howard Regional Healthcare System Kokomo, Indiana  46904
Saint Anthony Memorial Health Center Michigan City, Indiana  46360
Reid Hospital and Health Care Services Richmond, Indiana  47374
Saint Joseph's Medical Center South Bend, Indiana  46617
Constantinou, Costas L MD (UIA Investigator) Bettendorf, Iowa  52722
Cedar Rapids Oncology Association Cedar Rapids, Iowa  52403
Mercy Hospital Cedar Rapids, Iowa  52403
Medical Oncology and Hematology Associates-West Des Moines Clive, Iowa  50325
Iowa Oncology Research Association CCOP Des Moines, Iowa  50309
Mercy Capitol Des Moines, Iowa  50307
Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des Moines Des Moines, Iowa  50309
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Siouxland Hematology - Oncology Associates Sioux City, Iowa  51101
Hickman Cancer Center Adrian, Michigan  49221
Grand Rapids Clinical Oncology Program Grand Rapids, Michigan  49503
Saint Mary's Health Care Grand Rapids, Michigan  49503
Spectrum Health at Butterworth Campus Grand Rapids, Michigan  49503
Mercy Memorial Hospital Monroe, Michigan  48162
Mercy Health Partners-Mercy Campus Muskegon, Michigan  49443
Mercy Health Partners-Hackley Campus Muskegon, Michigan  49442
Lakeland Hospital St. Joseph, Michigan  49085
Merit Care Clinic Bemidji Bemidji, Minnesota  56601
Saint Mary's Medical Center Duluth, Minnesota  55805
Miller-Dwan Hospital Duluth, Minnesota  55805
Duluth Clinic CCOP Duluth, Minnesota  55805
Unity Hospital Fridley, Minnesota  55432
Saint John's Hospital - Healtheast Maplewood, Minnesota  55109
Minnesota Oncology Hematology PA-Maplewood Maplewood, Minnesota  55109
North Memorial Medical Health Center Robbinsdale, Minnesota  55422
Park Nicollet Clinic - Saint Louis Park Saint Louis Park, Minnesota  55416
Minnesota Oncology and Hematology PA-Woodbury Woodbury, Minnesota  55125
Hematology-Oncology Centers of the Northern Rockies PC Billings, Montana  59101
Saint Vincent Healthcare Billings, Montana  59101
Billings Clinic Billings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment Center Butte, Montana  59701
Berdeaux, Donald MD (UIA Investigator) Great Falls, Montana  59405
Saint Peter's Community Hospital Helena, Montana  59601
Glacier Oncology PLLC Kalispell, Montana  59901
Community Medical Hospital Missoula, Montana  59801
Saint Patrick Hospital - Community Hospital Missoula, Montana  59802
Saint Alexius Medical Center Bismarck, North Dakota  58501
Medcenter One Health Systems Bismarck, North Dakota  58501
Meritcare Hospital Fargo, North Dakota  58122
Doctors Hospital Columbus, Ohio  43228
Grant Medical Center Columbus, Ohio  43215
Mount Carmel Health Center West Columbus, Ohio  43222
Good Samaritan Hospital - Dayton Dayton, Ohio  45406
Dayton CCOP Dayton, Ohio  45429
Samaritan North Health Center Dayton, Ohio  45415
Hematology Oncology Center Incorporated Elyria, Ohio  44035
Blanchard Valley Hospital Findlay, Ohio  45840
Atrium Medical Center-Middletown Regional Hospital Franklin, Ohio  45005-1066
Kettering Medical Center Kettering, Ohio  45429
Marietta Memorial Hospital Marietta, Ohio  45750
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center Maumee, Ohio  43537
Bayview Oncology Associates Oregon, Ohio  43616
Saint Charles Hospital Oregon, Ohio  43616
North Coast Cancer Care Sandusky, Ohio  44870
Flower Memorial Hospital Sylvania, Ohio  43560
Toledo Community Hospital Oncology Program CCOP Toledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy Hospital Toledo, Ohio  43623
University of Toledo Toledo, Ohio  43614
The Toledo Hospital Toledo, Ohio  43606
Saint Vincent Mercy Medical Center Toledo, Ohio  43608
Upper Valley Medical Center Troy, Ohio  45373
Saint Ann's Hospital Westerville, Ohio  43081
Genesis HealthCare System Zanesville, Ohio  43701
Geisinger South Wilkes Barre-Hazelton Cancer Center Hazleton, Pennsylvania  18201
Geisinger Wyoming Valley Wilkes-Barre, Pennsylvania  18711
AnMed Health Hospital Anderson, South Carolina  29621
Upstate Carolina CCOP Spartanburg, South Carolina  29303
Fredericksburg Oncology Inc Fredericksburg, Virginia  22401
Mayo Clinic Health System Eau Claire Hospital - Luther Campus Eau Claire, Wisconsin  54703
Midelfort Clinic-Clairemont Campus Eau Claire, Wisconsin  54702
Central Wisconsin Cancer Program Fond Du Lac, Wisconsin  54935
Illinois CancerCare-Bloomington Bloomington%, Illinois  61701
Illinois CancerCare-Canton Canton, Illinois  61520
Illinois CancerCare-Carthage Carthage, Illinois  62321
Illinois CancerCare-Eureka Eureka, Illinois  61530
Illinois CancerCare-Cottage Galesburg, Illinois  61401
Illinois CancerCare-Galesburg Galesburg, Illinois  61401
Illinois CancerCare-Havana Havana, Illinois  62644
Illinois CancerCare-Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare-Macomb Macomb, Illinois  61455
Illinois CancerCare-Monmouth Monmouth, Illinois  61462
Illinois CancerCare-Community Cancer Center Normal, Illinois  61761
Illinois CancerCare-Pekin Pekin, Illinois  61603
Illinois CancerCare-Peru Peru, Illinois  61354
Illinois CancerCare-Princeton Princeton, Illinois  61356
Illinois CancerCare-Spring Valley Spring Valley, Illinois  61362
Fergus Falls Medical Group PA Fergus Falls, Minnesota  56537
North Coast Cancer Care-Clyde Clyde, Ohio  43410