Know Cancer

forgot password

Phase II Trial of Bevacizumab in Combination With Sorafenib in Recurrent Glioblastoma Multiforme

Phase 2
18 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

Phase II Trial of Bevacizumab in Combination With Sorafenib in Recurrent Glioblastoma Multiforme



- Identify the clinical efficacy of bevacizumab and sorafenib, as measured by 6-month
progression-free survival, in patients with recurrent glioblastoma multiforme.

- Assess the safety and toxicity of this regimen in this patient population.


- Assess time to progression and overall survival of this patient population.

- Assess the utility of dynamic contrast-enhanced MRI as a predictor of response to this
treatment regimen.

- Determine the relationship between tumor biomarkers and circulating biomarkers of
vascular response and clinical outcome in patients treated with this regimen.

- Assess the impact of treatment on the patient's quality of life using the FACTBr.

- Bank leftover tissue and blood products (i.e., plasma, DNA, and buffy coat) for future
research studies.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib once daily on days 1-14 and bevacizumab IV over 30-90
minutes on day 1. Courses repeat every 14 days in the absence of disease progression or
unacceptable toxicity.

Patients undergo blood and plasma sample collection at baseline and then periodically during
study treatment for translational research studies. Translational research studies include
analysis of circulating endothelial cells and circulating endothelial progenitor cells by
flow cytometry and measurement of angiogenic proteins in plasma by ELISA. DNA and buffy coat
are extracted and collected from the blood samples for pharmacogenetic studies.

Quality of life is assessed at baseline, prior to every other treatment course, and at the
end of treatment.

After completion of study treatment, patients are followed at 28-42 days, every 3 months for
5 years, and then annually for 10 years.

Inclusion Criteria


- Histologically confirmed glioblastoma multiforme as determined by pre-registration
central pathology review

- Gliosarcoma allowed

- Must have evidence of tumor progression by MRI or CT scan following radiotherapy or
the most recent anti-tumor therapy

- No more than 1 chemotherapy regimen for progressive or recurrent disease

- Bidimensionally measurable or evaluable disease by MRI or CT scan

- No evidence of CNS hemorrhage on baseline CT or MRI

- Patients with T1 hyperintensity confined to the surgical cavity which is felt
likely due to post surgical blood contaminating the intracavity cerebrospinal
fluid or irrigation that have not yet absorbed and which is not felt to
clinically or radiographically represent new spontaneous hemorrhage are eligible

- Patients with old blood products or hemosiderin without a history of spontaneous
bleeding are eligible


- ECOG performance status 0-2

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin > 9.0 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal

- AST ≤ 3 times upper limit of normal

- Creatinine ≤ upper limit of normal

- Urine protein:creatinine ratio < 1 OR urine protein < 1,000 mg by 24-hour urine

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for six months after
completion of study treatment

- Able to complete questionnaire(s) alone or with assistance

- Willing to return to NCCTG enrolling institution for follow-up

- Willing to provide mandatory blood samples for research purposes

- Not immunocompromised (other than that related to the use of corticosteroids)

- No known HIV positivity

- No concurrent uncontrolled illness including, but not limited to, the following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study

- No inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 150 mm
Hg or diastolic BP > 100 mm Hg while on antihypertensive medications)

- Patients with well-controlled hypertension are eligible

- No myocardial infarction or unstable angina within the past 6 months

- No congestive heart failure requiring the use of ongoing maintenance therapy for
life-threatening ventricular arrhythmias

- No New York Heart Association class II-IV congestive heart failure

- No significant vascular disease (e.g., aortic aneurysm or aortic dissection)

- No peripheral arterial thrombosis within the past 6 months

- No stroke or transient ischemic attack within the past 6 months

- No history of hypertensive crisis or hypertensive encephalopathy

- No evidence of bleeding diathesis (greater than normal risk of bleeding) or
coagulopathy (in the absence of therapeutic anticoagulation)

- No active or recent history of hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per
episode) within the past 30 days

- No serious, nonhealing wounds, ulcers, or bone fractures

- No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract
disease resulting in an inability to take oral medication or a requirement for IV

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 6 months

- No significant traumatic injury within the past 28 days

- No known hypersensitivity to any of the components of sorafenib or bevacizumab

- No other active malignancy within the past 3 years, except nonmelanoma skin cancer or
carcinoma in situ of the cervix

- Patients with a history of prior malignancy must not be receiving specific
treatment (other than hormonal therapy) for that malignancy

- No co-morbid systemic illness or other concurrent severe disease that, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or significantly interfere with the proper assessment of safety and
toxicity of the prescribed study regimen


- See Disease Characteristics

- At least 12 weeks since prior radiotherapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

- More than 2 weeks since prior small molecule cell cycle inhibitors

- At least 1 week since prior fixed-dose corticosteroids (or no corticosteroids)

- No prior intratumoral chemotherapy, stereotactic radiosurgery or interstitial
brachytherapy unless there is a separate lesion on MRI that is not part of the prior
treatment field OR there is proof of recurrent disease based on biopsy, MRI
spectroscopy, or PET scan

- No prior antiangiogenic therapy

- No prior surgical procedures affecting absorption

- More than 7 days since prior core biopsy or other minor surgical procedures

- Placement of a vascular access device is allowed

- More than 28 days since prior major surgical procedure or open biopsy

- No concurrent major surgical procedure

- No other concurrent investigational agents

- No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, fosphenytoin,
carbamazepine, phenobarbital, or primidone)

- No other concurrent potent CYP3A4 inducers (e.g., rifampin or St. John's wort)

- No concurrent therapeutic anticoagulation with warfarin

- Prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial
access devices allowed provided the INR < 1.5

- Therapeutic anticoagulation with low molecular weight heparin allowed

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

6-month progression-free survival

Safety Issue:


Principal Investigator

Evanthia Galanis, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




Start Date:

September 2008

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • recurrent adult brain tumor
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms



Mayo Clinic Scottsdale Scottsdale, Arizona  85259
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905
CCOP - Upstate Carolina Spartanburg, South Carolina  29303
CCOP - Wichita Wichita, Kansas  67214-3882
Hurley Medical Center Flint, Michigan  48503
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Carle Cancer Center Urbana, Illinois  61801
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Rush-Copley Cancer Care Center Aurora, Illinois  60507
Carle Cancer Center at Carle Foundation Hospital Urbana, Illinois  61801
Cedar Rapids Oncology Associates Cedar Rapids, Iowa  52403
Mercy Medical Center - Sioux City Sioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
St. Luke's Regional Medical Center Sioux City, Iowa  51104
CCOP - Michigan Cancer Research Consortium Ann Arbor, Michigan  48106
Saint Joseph Mercy Cancer Center Ann Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical Center Dearborn, Michigan  48123-2500
Genesys Hurley Cancer Institute Flint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical Center Grosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer Center Lansing, Michigan  48912-1811
St. John Macomb Hospital Warren, Michigan  48093
MeritCare Bemidji Bemidji, Minnesota  56601
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - Duluth Duluth, Minnesota  55805-1983
CCOP - Duluth Duluth, Minnesota  55805
Miller - Dwan Medical Center Duluth, Minnesota  55805
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - Maplewood Maplewood, Minnesota  55109
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
MeritCare Broadway Fargo, North Dakota  58122
CCOP - MeritCare Hospital Fargo, North Dakota  58122
Geisinger Medical Group - Scenery Park State College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PC Sioux Falls, South Dakota  57105
Rapid City Regional Hospital Rapid City, South Dakota  57709
CCOP - Cancer Research for the Ozarks Springfield, Missouri  65807
CCOP - Montana Cancer Consortium Billings, Montana  59101
CCOP - Columbus Columbus, Ohio  43206
CCOP - Dayton Kettering, Ohio  45429
Charles M. Barrett Cancer Center at University Hospital Cincinnati, Ohio  45267-0526
CCOP - Columbia River Oncology Program Portland, Oregon  97225
John Stoddard Cancer Center at Iowa Methodist Medical Center Des Moines, Iowa  50309
St. Vincent Mercy Medical Center Toledo, Ohio  43608
Hulston Cancer Center at Cox Medical Center South Springfield, Missouri  65807
St. John's Regional Health Center Springfield, Missouri  65804
CCOP - Toledo Community Hospital Toledo, Ohio  43623-3456
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Medical University of Ohio Cancer Center Toledo, Ohio  43614
Toledo Hospital Toledo, Ohio  43606
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa Regional Ottumwa, Iowa  52501
Green Bay Oncology, Limited - Escanaba Escanaba, Michigan  49431
Dickinson County Healthcare System Iron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green Bay Green Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical Center Marinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto Falls Oconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon Bay Sturgeon Bay, Wisconsin  54235
Baptist Cancer Institute - Jacksonville Jacksonville, Florida  32207
Southwest Medical Center Liberal, Kansas  67901
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - Billings Billings, Montana  59101
St. Peter's Hospital Helena, Montana  59601
Kalispell Regional Medical Center Kalispell, Montana  59901
Glacier Oncology, PLLC Kalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula, Montana  59802
Montana Cancer Specialists at Montana Cancer Center Missoula, Montana  59802
Community Medical Center Missoula, Montana  59801
Adena Regional Medical Center Chillicothe, Ohio  54601
Doctors Hospital at Ohio Health Columbus, Ohio  43228
Riverside Methodist Hospital Cancer Care Columbus, Ohio  43214
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial Hospital Marietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial Hospital Newark, Ohio  43055
Community Hospital of Springfield and Clark County Springfield, Ohio  45505
Genesis - Good Samaritan Hospital Zanesville, Ohio  43701
Knight Cancer Institute at Oregon Health and Science University Portland, Oregon  97239-3098
Geisinger Cancer Institute at Geisinger Health Danville, Pennsylvania  17822-0001
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center Hartford, Connecticut  06105
Mount Carmel Health - West Hospital Columbus, Ohio  43222
Front Range Cancer Specialists Fort Collins, Colorado  80528
St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove, Indiana  46107
Mercy Regional Cancer Center at Mercy Medical Center Cedar Rapids, Iowa  52403
John Stoddard Cancer Center at Iowa Lutheran Hospital Des Moines, Iowa  50316-2301
Mercy Capitol Hospital Des Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer Center Des Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer Center Des Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des Moines Des Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des Moines West Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical Center Adrian, Michigan  49221
Community Cancer Center of Monroe Monroe, Michigan  48162
Alexandria, Minnesota  56308
Coborn Cancer Center Saint Cloud, Minnesota  56303
CentraCare Clinic - River Campus St. Cloud, Minnesota  56303
Immanuel Medical Center Omaha, Nebraska  68122
Creighton University Medical Center Omaha, Nebraska  68131-2197
Bismarck Cancer Center Bismarck, North Dakota  58501
Wood County Oncology Center Bowling Green, Ohio  43402
Samaritan North Cancer Care Center Dayton, Ohio  45415
Grandview Hospital Dayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley Hospital Dayton, Ohio  45409
Good Samaritan Hospital Dayton, Ohio  45406
Blanchard Valley Medical Associates Findlay, Ohio  45840
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Lima Memorial Hospital Lima, Ohio  45804
St. Luke's Hospital Maumee, Ohio  43537
Northwest Ohio Oncology Center Maumee, Ohio  43537
Middletown Regional Hospital Middletown, Ohio  45044
Toledo Clinic - Oregon Oregon, Ohio  43616
St. Charles Mercy Hospital Oregon, Ohio  43616
North Coast Cancer Care, Incorporated Sandusky, Ohio  44870
Mercy Medical Center Springfield, Ohio  45504
Mercy Hospital of Tiffin Tiffin, Ohio  44883
Toledo Clinic, Incorporated - Main Clinic Toledo, Ohio  43623
UVMC Cancer Care Center at Upper Valley Medical Center Troy, Ohio  45373-1300
Fulton County Health Center Wauseon, Ohio  43567
Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia, Ohio  45385
Providence Milwaukie Hospital Milwaukie, Oregon  97222
Providence Cancer Center at Providence Portland Medical Center Portland, Oregon  97213-2967
Providence St. Vincent Medical Center Portland, Oregon  97225
Southwest Washington Medical Center Cancer Center Vancouver, Washington  98668
Holy Family Memorial Medical Center Cancer Care Center Manitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial Hospital Sheridan, Wyoming  82801
Cancer Resource Center - Lincoln Lincoln, Nebraska  68510
Midelfort Clinic - Luther Eau Claire, Wisconsin  54702
Reid Hospital & Health Care Services Richmond, Indiana  47374
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas - Fort Scott Fort Scott, Kansas  66701
Cancer Center of Kansas-Independence Independence, Kansas  67301
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Lawrence Memorial Hospital Lawrence, Kansas  66044
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Drs. Carrol, Sheth, Raghavan Louisville, Kentucky  40215
Foote Memorial Hospital Jackson, Michigan  49201
Haematology-Oncology Associates of Ohio and Michigan, PC Lambertville, Michigan  48144
St. Mary Mercy Hospital Livonia, Michigan  48154
Mercy Memorial Hospital - Monroe Monroe, Michigan  48162
St. Joseph Mercy Oakland Pontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy Hospital Port Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - Saginaw Saginaw, Michigan  48601
Fergus Falls Medical Group, PA Fergus Falls, Minnesota  56537
Billings Clinic - Downtown Billings, Montana  59107-7000
Bozeman Deaconess Cancer Center Bozeman, Montana  59715
St. James Healthcare Cancer Care Butte, Montana  59701
Great Falls Clinic - Main Facility Great Falls, Montana  59405
Northern Montana Hospital Havre, Montana  59501
Kalispell Medical Oncology at KRMC Kalispell, Montana  59901
Alegant Health Cancer Center at Bergan Mercy Medical Center Omaha, Nebraska  68124
Mary Rutan Hospital Bellefontaine, Ohio  43311
North Coast Cancer Care - Clyde Clyde, Ohio  43410
Grant Medical Center Cancer Care Columbus, Ohio  43215
Hematology Oncology Center Elyria, Ohio  44035
Wayne Hospital Greenville, Ohio  45331
Fisher-Titus Medical Center Norwalk, Ohio  44857
Flower Hospital Cancer Center Sylvania, Ohio  43560
St. Anne Mercy Hospital Toledo, Ohio  43623
Mount Carmel St. Ann's Cancer Center Westerville, Ohio  43081
Clinton Memorial Hospital Wilmington, Ohio  45177
Adventist Medical Center Portland, Oregon  97216
Legacy Good Samaritan Hospital & Comprehensive Cancer Center Portland, Oregon  97210
Northwest Cancer Specialists at Rose Quarter Cancer Center Portland, Oregon  97227
Geisinger Hazleton Cancer Center Hazleton, Pennsylvania  18201
Fredericksburg Oncology, Incorporated Fredericksburg, Virginia  22401
Rocky Mountain Oncology Casper, Wyoming  82609
Mid Dakota Clinic, PC Bismarck, North Dakota  58501
Rutherford Hospital Rutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Great Falls, Montana  59405
Guardian Oncology and Center for Wellness Missoula, Montana  59804
St. Vincent Healthcare Cancer Care Services Billings, Montana  59101
AnMed Cancer Center Anderson, South Carolina  29621
Medcenter One Hospital Cancer Care Center Bismarck, North Dakota  58501
St. Alexius Medical Center Cancer Center Bismarck, North Dakota  58502
Precision Radiotherapy at University Pointe West Chester, Ohio  45069
Cancer Care Associates Fresno, California  93720
Luther Midlelfort Hospital Eau Claire, Wisconsin  54702