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A Phase III Randomized Study of Imatinib, With or Without Bevacizumab (NSC-704865), in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Gastrointestinal Stromal Tumor

Thank you

Trial Information

A Phase III Randomized Study of Imatinib, With or Without Bevacizumab (NSC-704865), in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors


PRIMARY OBJECTIVES:

I. Compare the progression-free survival of patients with metastatic or unresectable
gastrointestinal stromal tumor treated with imatinib mesylate with vs without bevacizumab.

II. Compare the response probabilities (in patients with measurable disease) and overall
survival rates in patients treated with these regimens.

III. Compare the frequency and severity of toxicities associated with these regimens in
these patients.

IV. Correlate soluble vascular endothelial growth factor (VEGF), VEGF-D, VEGF receptor
(VEGFR)-1, VEGFR-2, angiopoietin-2, platelet-derived growth factor receptor (PDGFR)-AA and
PDGFR-BB levels, positron-emission tomography imaging, and immunohistochemistry for p16,
VEGF, and VEGFR with kinase mutation status and clinical outcomes.

V. Examine the pharmacokinetics of imatinib mesylate with single nucleotide polymorphisms
involving the ABCG2 and CYP3A4 genes, as well as other genes that are reported to influence
the absorption, distribution, metabolism, and elimination of imatinib mesylate.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
Zubrod performance status (0 vs 1-3) and disease status (measurable vs non-measurable).
Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral imatinib mesylate once daily on days 1-21 and bevacizumab IV
over 30-90 minutes on day 1.

ARM II: Patients receive oral imatinib mesylate once daily on days 1-21.

In both arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

Blood* is obtained at baseline, periodically during study treatment, and at disease
progression. Blood is analyzed for angiogenesis-related soluble factors, kinase genotyping,
pharmacokinetics, and pharmacogenomics.

[Note: *Samples are no longer considered mandatory for study as of 5/29/2009.]

After completion of study treatment, patients are followed periodically for up to 7 years.

Inclusion Criteria


Criteria:

- Histologically confirmed gastrointestinal stromal tumor (GIST)

- Metastatic or unresectable disease

- Determined to be unresectable for cure

- Measurable and/or nonmeasurable disease by MRI or CT scan

- No known brain metastasis

- Zubrod performance status 0-3

- Platelet count >= 100,000/mm^3

- Absolute neutrophil count >=1,000/mm^3

- Hemoglobin >= 9 g/dL (transfusion allowed)

- Bilirubin =< 2.0 times upper limit of normal (ULN)

- SGOT/SGPT =< 2.5 times ULN (5 times ULN with liver involvement)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for up to 6
months after completion of study treatment

- No cerebrovascular accident, transient ischemic attack, myocardial infarction, or
unstable angina within the past 6 months

- No serious cardiac arrhythmia requiring medication

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

- No clinically significant peripheral vascular disease

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No contraindication to oral medications (e.g., severe dysphagia)

- G- or J-tubes allowed

- No history of hypertension unless well controlled (i.e., blood pressure < 160/90 mm
Hg) and on a stable regimen of antihypertensive therapy

- No serious nonhealing wound, ulcer, or bone fracture

- No other prior malignancy except for any of the following: adequately treated basal
cell or squamous cell skin cancer; in situ cervical cancer; adequately treated stage
I or II cancer that is currently in complete remission; any other cancer for which
the patient has been disease free for >= 5 years

- No significant traumatic injury in the past 28 days

- Recovered from prior therapy

- At least 28 days since prior chemotherapy

- At least 28 days since prior radiotherapy

- Evidence of progressive disease within the radiation field or disease outside the
radiation field

- No prior bevacizumab or other agents targeting vascular endothelial growth factor
(VEGF), VEGF receptor, or platelet-derived growth factor receptor (PDGFR) for
advanced disease

- These agents may have been used in the adjuvant setting provided no recurrence for >=
12 months after completion of therapy

- More than 28 days since prior major surgery or open biopsy

- No anticipated need for major surgery

- More than 7 days since prior fine-needle aspiration or core biopsies

- More than 7 days since prior procedure to place a portacath

- No other concurrent anticancer biologic agents, chemotherapy, radiotherapy, or any
other anticancer agents

- No concurrent therapeutic warfarin for anticoagulation

- Concurrent low-molecular weight heparin or other agents for therapeutic
anticoagulation or mini-dose warfarin for prophylaxis allowed

- No other concurrent investigational agents

- Creatinine =< 1.5 times ULN

- Urine protein:creatinine ratio < 1

- INR =< 1.5

- PTT normal

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Investigator-assessed progression-free survival

Outcome Description:

Analyzed using stratified logrank statistic, calculated from the stratified Cox-model.

Outcome Time Frame:

Up to 7 years

Safety Issue:

No

Principal Investigator

Charles Blanke

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00776

NCT ID:

NCT00324987

Start Date:

April 2008

Completion Date:

Related Keywords:

  • Gastrointestinal Stromal Tumor
  • Gastrointestinal Stromal Tumors

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
University of Washington Medical CenterSeattle, Washington  98195-6043
Hurley Medical CenterFlint, Michigan  48503
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Hutchinson Area Health CareHutchinson, Minnesota  55350
Meeker County Memorial HospitalLichfield, Minnesota  55355
Rapid City Regional HospitalRapid City, South Dakota  57709
Marshfield ClinicMarshfield, Wisconsin  54449
Sutter Health Western Division Cancer Research GroupGreenbrae, California  94904
South Georgia Medical CenterValdosta, Georgia  31603
Virginia Piper Cancer InstituteMinneapolis, Minnesota  55407
Via Christi Regional Medical CenterWichita, Kansas  67214
Iowa Methodist Medical CenterDes Moines, Iowa  50309
Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Group Health CooperativeSeattle, Washington  98112
Great Falls ClinicGreat Falls, Montana  59405
Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Cancer Center of Kansas - ChanuteChanute, Kansas  66720
Cancer Center of Kansas - Dodge CityDodge City, Kansas  67801
Cancer Center of Kansas - NewtonNewton, Kansas  67114
Cancer Center of Kansas - SalinaSalina, Kansas  67042
Cancer Center of Kansas - WellingtonWellington, Kansas  67152
Associates in Womens HealthWichita, Kansas  67203
Cancer Center of Kansas - WinfieldWinfield, Kansas  67156
Northern Rockies Radiation Oncology CenterBillings, Montana  59101
Bozeman Deaconess HospitalBozeman, Montana  59715
Kalispell Medical OncologyKalispell, Montana  59901
Kalispell Regional Medical CenterKalispell, Montana  59901
Harborview Medical CenterSeattle, Washington  98104
Cancer Care Northwest - Spokane SouthSpokane, Washington  99202
Welch Cancer CenterSheridan, Wyoming  82801
Sutter Solano Medical CenterVallejo, California  94589
Genesis Medical Center - West CampusDavenport, Iowa  52804
Salina Regional Health CenterSalina, Kansas  67401
Community Cancer Center of MonroeMonroe, Michigan  48162
Bismarck Cancer CenterBismarck, North Dakota  58501
Grandview HospitalDayton, Ohio  45405
Lima Memorial HospitalLima, Ohio  45804
Mercy Hospital of TiffinTiffin, Ohio  44883
Fulton County Health CenterWauseon, Ohio  43567
Medical Oncology and Hematology AssociatesDes Moines, Iowa  50309
Bixby Medical CenterAdrian, Michigan  49221
Saint Joseph Mercy HospitalAnn Arbor, Michigan  48106
Regions HospitalSaint Paul, Minnesota  55101
Saint Francis Regional Medical CenterShakopee, Minnesota  55379
Saint Luke's HospitalMaumee, Ohio  43537
Miami Valley HospitalDayton, Ohio  45409
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Lawrence Memorial HospitalLawrence, Kansas  66044
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
Northern Montana HospitalHavre, Montana  59501
Wayne HospitalGreenville, Ohio  45331
Clinton Memorial HospitalWilmington, Ohio  45177
Adventist Medical CenterPortland, Oregon  97216
Marshfield Clinic Cancer Care at Regional Cancer CenterEau Claire, Wisconsin  54701
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Diagnostic and Treatment CenterWeston, Wisconsin  54476
Marshfield Clinic - Wisconsin Rapids CenterWisconsin Rapids, Wisconsin  54494
Greene Memorial HospitalXenia, Ohio  45385
Memorial Medical CenterSpringfield, Illinois  62781
La Grange Memorial HospitalLa Grange, Illinois  60525
Guardian Oncology and Center for WellnessMissoula, Montana  59804
Woodwinds Health CampusWoodbury, Minnesota  55125
Hennepin County Medical CenterMinneapolis, Minnesota  
University of RochesterRochester, New York  14642
Glens Falls HospitalGlens Falls, New York  12801
California Pacific Medical CenterSan Francisco, California  94115
Mid Dakota ClinicBismarck, North Dakota  58501
Wichita CCOPWichita, Kansas  67214-3882
Montana Cancer Consortium CCOPBillings, Montana  59101
Flower HospitalSylvania, Ohio  43560-2197
Providence HospitalSouthfield, Michigan  48075
Decatur Memorial HospitalDecatur, Illinois  62526
Montana Cancer SpecialistsMissoula, Montana  59807-7877
Memorial Health University Medical CenterSavannah, Georgia  31404
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
University of Southern CaliforniaLos Angeles, California  90033
University of CincinnatiCincinnati, Ohio  45267-0502
Mills - Peninsula HospitalsBurlingame, California  94010
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
John B Amos Cancer CenterColumbus, Georgia  31904
Rush - Copley Medical CenterAurora, Illinois  60504
Resurrection HealthcareChicago, Illinois  60631
Joliet Oncology-Hematology Associates LimitedJoliet, Illinois  60435
Carle Clinic-Urbana MainUrbana, Illinois  61801
Saint Francis Hospital and Health CentersBeech Grove, Indiana  46107
Saint Anthony Memorial Health CenterMichigan City, Indiana  46360
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
McFarland ClinicAmes, Iowa  50010
Medical Oncology and Hematology Associates-West Des MoinesClive, Iowa  50325
Genesis Medical Center - East CampusDavenport, Iowa  52803
Iowa Oncology Research Association CCOPDes Moines, Iowa  50309
Mercy CapitolDes Moines, Iowa  50307
Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates-Des MoinesDes Moines, Iowa  50309
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cancer Center of Kansas - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas-KingmanKingman, Kansas  67068
Cancer Center of Kansas - ParsonsParsons, Kansas  67357
Cancer Center of Kansas - PrattPratt, Kansas  67124
Cancer Center of Kansas-Wichita Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas - Main OfficeWichita, Kansas  67214
Hickman Cancer CenterAdrian, Michigan  49221
Michigan Cancer Research Consortium Community Clinical Oncology ProgramAnn Arbor, Michigan  48106
Oakwood HospitalDearborn, Michigan  48123
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Allegiance HealthJackson, Michigan  49201
Sparrow HospitalLansing, Michigan  48912
Saint Mary Mercy HospitalLivonia, Michigan  48154
Mercy Memorial HospitalMonroe, Michigan  48162
Saint Joseph Mercy OaklandPontiac, Michigan  48341-2985
Saint Joseph Mercy Port HuronPort Huron, Michigan  48060
Saint Mary's of MichiganSaginaw, Michigan  48601
Saint John Macomb-Oakland HospitalWarren, Michigan  48093
Miller-Dwan HospitalDuluth, Minnesota  55805
Saint John's Hospital - HealtheastMaplewood, Minnesota  55109
Saint Joseph's Hospital - HealtheastSaint Paul, Minnesota  55102
Ozark Health Ventures LLC dba Cancer Research for The Ozarks SpringfieldSpringfield, Missouri  65802
Saint John's HospitalSpringfield, Missouri  65804
Hematology-Oncology Centers of the Northern Rockies PCBillings, Montana  59101
Saint Vincent HealthcareBillings, Montana  59101
Billings ClinicBillings, Montana  59107-7000
Saint James Community Hospital and Cancer Treatment CenterButte, Montana  59701
Berdeaux, Donald MD (UIA Investigator)Great Falls, Montana  59405
Saint Peter's Community HospitalHelena, Montana  59601
Glacier Oncology PLLCKalispell, Montana  59901
Community Medical HospitalMissoula, Montana  59801
Saint Patrick Hospital - Community HospitalMissoula, Montana  59802
Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington CountyMount Holly, New Jersey  08060
Virtua West Jersey Hospital VoorheesVoorhees, New Jersey  08043
Orange Regional Medical CenterMiddletown, New York  10940
Interlakes Foundation Inc-RochesterRochester, New York  14623
Highland HospitalRochester, New York  14620
Kinston Medical Specialists PAKinston, North Carolina  28501
Saint Alexius Medical CenterBismarck, North Dakota  58501
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Veteran Affairs Medical CenterDayton, Ohio  45428
Hematology Oncology Center IncorporatedElyria, Ohio  44035
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Toledo Radiation Oncology at Northwest Ohio Onocolgy CenterMaumee, Ohio  43537
Saint Charles HospitalOregon, Ohio  43616
North Coast Cancer CareSandusky, Ohio  44870
Toledo Community Hospital Oncology Program CCOPToledo, Ohio  43617
Mercy Cancer Center at Saint Anne Mercy HospitalToledo, Ohio  43623
University of ToledoToledo, Ohio  43614
Saint Vincent Mercy Medical CenterToledo, Ohio  43608
Upper Valley Medical CenterTroy, Ohio  45373
Audie L Murphy Veterans Affairs HospitalSan Antonio, Texas  78209
University HospitalSan Antonio, Texas  78229
Fredericksburg Oncology IncFredericksburg, Virginia  22401
Harrison Bremerton Hematology and OncologyBremerton, Washington  98310
Columbia Basin Hematology and Oncology PLLCKennewick, Washington  99336
Minor and James Medical PLLCSeattle, Washington  98104
The PolyclinicSeattle, Washington  98122
Swedish Medical Center-First HillSeattle, Washington  98122-4307
Sacred Heart HospitalEau Claire, Wisconsin  54701
Marshfield Clinic-Minocqua CenterMinocqua, Wisconsin  54548
Marshfield Clinic at James Beck Cancer CenterRhinelander, Wisconsin  54501
Marshfield Clinic-Rice Lake CenterRice Lake, Wisconsin  54868
Saint Michael's HospitalStevens Point, Wisconsin  54481
Marshfield Clinic-Wausau CenterWausau, Wisconsin  54401
Oncology Care Associates PLLCSt. Joseph, Michigan  49085
Marin General HospitalGreenbrae, California  94904
North Coast Cancer Care-ClydeClyde, Ohio  43410
West Virginia University CharlestonCharleston, West Virginia  25304
Marshfield Clinic-Chippewa CenterChippewa Falls, Wisconsin  54729
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Alta Bates Summit Medical Center-Herrick CampusBerkeley, California  94704
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Southwest Oncology GroupSan Antonio, Texas  78245
The Toledo Hospital/Toledo Children's HospitalToledo, Ohio  43606
Genesys Regional Medical Center-West Flint CampusFlint, Michigan  48532
Essentia Health Duluth Clinic CCOPDuluth, Minnesota  55805
Essentia Health Saint Mary's Medical CenterDuluth, Minnesota  55805
Sanford Bismarck Medical CenterBismarck, North Dakota  58501
Toledo Clinic Cancer Centers-OregonOregon, Ohio  43616
PeaceHealth Saint Joseph Medical CenterBellingham, Washington  98225
Edward Hospital/Cancer CenterNaperville, Illinois  60540
Toledo Clinic Cancer Centers-Bowling GreenBowling Green, Ohio  43402
Toledo Clinic Cancer Centers-MaumeeMaumee, Ohio  43537-1839
Toledo Clinic Cancer Centers-ToledoToledo, Ohio  43623
Geisinger South Wilkes-BarreWilkes-Barre, Pennsylvania  18765