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


Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

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


OBJECTIVES:

Primary

- 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.

Secondary

- 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


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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
collection

- 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
requirements

- 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
alimentation)

- 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

PRIOR CONCURRENT THERAPY:

- 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:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

6-month progression-free survival

Safety Issue:

No

Principal Investigator

Evanthia Galanis, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000587614

NCT ID:

NCT00621686

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

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic - JacksonvilleJacksonville, Florida  32224
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - Upstate CarolinaSpartanburg, South Carolina  29303
CCOP - WichitaWichita, Kansas  67214-3882
Hurley Medical CenterFlint, Michigan  48503
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Carle Cancer CenterUrbana, Illinois  61801
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
CCOP - Michigan Cancer Research ConsortiumAnn Arbor, Michigan  48106
Saint Joseph Mercy Cancer CenterAnn Arbor, Michigan  48106-0995
Oakwood Cancer Center at Oakwood Hospital and Medical CenterDearborn, Michigan  48123-2500
Genesys Hurley Cancer InstituteFlint, Michigan  48503
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Sparrow Regional Cancer CenterLansing, Michigan  48912-1811
St. John Macomb HospitalWarren, Michigan  48093
MeritCare BemidjiBemidji, Minnesota  56601
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
MeritCare BroadwayFargo, North Dakota  58122
CCOP - MeritCare HospitalFargo, North Dakota  58122
Geisinger Medical Group - Scenery ParkState College, Pennsylvania  16801
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Rapid City Regional HospitalRapid City, South Dakota  57709
CCOP - Cancer Research for the OzarksSpringfield, Missouri  65807
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
CCOP - ColumbusColumbus, Ohio  43206
CCOP - DaytonKettering, Ohio  45429
Charles M. Barrett Cancer Center at University HospitalCincinnati, Ohio  45267-0526
CCOP - Columbia River Oncology ProgramPortland, Oregon  97225
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
St. Vincent Mercy Medical CenterToledo, Ohio  43608
Hulston Cancer Center at Cox Medical Center SouthSpringfield, Missouri  65807
St. John's Regional Health CenterSpringfield, Missouri  65804
CCOP - Toledo Community HospitalToledo, Ohio  43623-3456
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Toledo HospitalToledo, Ohio  43606
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
McCreery Cancer Center at Ottumwa RegionalOttumwa, Iowa  52501
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
Baptist Cancer Institute - JacksonvilleJacksonville, Florida  32207
Southwest Medical CenterLiberal, Kansas  67901
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Montana Cancer Specialists at Montana Cancer CenterMissoula, Montana  59802
Community Medical CenterMissoula, Montana  59801
Adena Regional Medical CenterChillicothe, Ohio  54601
Doctors Hospital at Ohio HealthColumbus, Ohio  43228
Riverside Methodist Hospital Cancer CareColumbus, Ohio  43214
Grady Memorial HospitalDelaware, Ohio  43015
Fairfield Medical CenterLancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial HospitalMarietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial HospitalNewark, Ohio  43055
Community Hospital of Springfield and Clark CountySpringfield, Ohio  45505
Genesis - Good Samaritan HospitalZanesville, Ohio  43701
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical CenterHartford, Connecticut  06105
Mount Carmel Health - West HospitalColumbus, Ohio  43222
Front Range Cancer SpecialistsFort Collins, Colorado  80528
St. Francis Hospital and Health Centers - Beech Grove CampusBeech Grove, Indiana  46107
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Hickman Cancer Center at Bixby Medical CenterAdrian, Michigan  49221
Community Cancer Center of MonroeMonroe, Michigan  48162
Alexandria, Minnesota  56308
Coborn Cancer CenterSaint Cloud, Minnesota  56303
CentraCare Clinic - River CampusSt. Cloud, Minnesota  56303
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Bismarck Cancer CenterBismarck, North Dakota  58501
Wood County Oncology CenterBowling Green, Ohio  43402
Samaritan North Cancer Care CenterDayton, Ohio  45415
Grandview HospitalDayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley HospitalDayton, Ohio  45409
Good Samaritan HospitalDayton, Ohio  45406
Blanchard Valley Medical AssociatesFindlay, Ohio  45840
Charles F. Kettering Memorial HospitalKettering, Ohio  45429
Lima Memorial HospitalLima, Ohio  45804
St. Luke's HospitalMaumee, Ohio  43537
Northwest Ohio Oncology CenterMaumee, Ohio  43537
Middletown Regional HospitalMiddletown, Ohio  45044
Toledo Clinic - OregonOregon, Ohio  43616
St. Charles Mercy HospitalOregon, Ohio  43616
North Coast Cancer Care, IncorporatedSandusky, Ohio  44870
Mercy Medical CenterSpringfield, Ohio  45504
Mercy Hospital of TiffinTiffin, Ohio  44883
Toledo Clinic, Incorporated - Main ClinicToledo, Ohio  43623
UVMC Cancer Care Center at Upper Valley Medical CenterTroy, Ohio  45373-1300
Fulton County Health CenterWauseon, Ohio  43567
Ruth G. McMillan Cancer Center at Greene Memorial HospitalXenia, Ohio  45385
Providence Milwaukie HospitalMilwaukie, Oregon  97222
Providence Cancer Center at Providence Portland Medical CenterPortland, Oregon  97213-2967
Providence St. Vincent Medical CenterPortland, Oregon  97225
Southwest Washington Medical Center Cancer CenterVancouver, Washington  98668
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
Cancer Resource Center - LincolnLincoln, Nebraska  68510
Midelfort Clinic - LutherEau Claire, Wisconsin  54702
Reid Hospital & Health Care ServicesRichmond, Indiana  47374
McFarland Clinic, PCAmes, Iowa  50010
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Drs. Carrol, Sheth, RaghavanLouisville, Kentucky  40215
Foote Memorial HospitalJackson, Michigan  49201
Haematology-Oncology Associates of Ohio and Michigan, PCLambertville, Michigan  48144
St. Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial Hospital - MonroeMonroe, Michigan  48162
St. Joseph Mercy OaklandPontiac, Michigan  48341-2985
Mercy Regional Cancer Center at Mercy HospitalPort Huron, Michigan  48060
Seton Cancer Institute at Saint Mary's - SaginawSaginaw, Michigan  48601
Fergus Falls Medical Group, PAFergus Falls, Minnesota  56537
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Mary Rutan HospitalBellefontaine, Ohio  43311
North Coast Cancer Care - ClydeClyde, Ohio  43410
Grant Medical Center Cancer CareColumbus, Ohio  43215
Hematology Oncology CenterElyria, Ohio  44035
Wayne HospitalGreenville, Ohio  45331
Fisher-Titus Medical CenterNorwalk, Ohio  44857
Flower Hospital Cancer CenterSylvania, Ohio  43560
St. Anne Mercy HospitalToledo, Ohio  43623
Mount Carmel St. Ann's Cancer CenterWesterville, Ohio  43081
Clinton Memorial HospitalWilmington, Ohio  45177
Adventist Medical CenterPortland, Oregon  97216
Legacy Good Samaritan Hospital & Comprehensive Cancer CenterPortland, Oregon  97210
Northwest Cancer Specialists at Rose Quarter Cancer CenterPortland, Oregon  97227
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Fredericksburg Oncology, IncorporatedFredericksburg, Virginia  22401
Rocky Mountain OncologyCasper, Wyoming  82609
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Rutherford HospitalRutherfordton, North Carolina  28139
Gibbs Regional Cancer Center at Spartanburg Regional Medical CenterSpartanburg, South Carolina  29303
Great Falls, Montana  59405
Guardian Oncology and Center for WellnessMissoula, Montana  59804
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
AnMed Cancer CenterAnderson, South Carolina  29621
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502
Precision Radiotherapy at University PointeWest Chester, Ohio  45069
Cancer Care AssociatesFresno, California  93720
Luther Midlelfort HospitalEau Claire, Wisconsin  54702