Imatinib Mesylate With or Without Bevacizumab in Treating Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor (S0502)

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

This randomized phase III trial studies imatinib mesylate and bevacizumab to see how well they work compared to imatinib mesylate alone in treating patients with gastrointestinal stromal tumor that has spread to other parts of the body or cannot be removed by surgery. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. It is not yet known whether imatinib mesylate and bevacizumab are more effective than imatinib mesylate alone in treating gastrointestinal stromal tumor.

Study Overview

• Status: Terminated
• Conditions: Gastrointestinal Stromal Tumor
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Bevacizumab; Drug: Imatinib Mesylate

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether treatment with imatinib (imatinib mesylate) plus bevacizumab leads to improved progression free survival (PFS) versus treatment with imatinib alone in first-line treatment of incurable gastrointestinal stromal tumor (GIST).

SECONDARY OBJECTIVES:

I. To compare response probabilities (confirmed and unconfirmed complete response [CR] and partial response [PR] for subset of patients with measurable disease), overall survival, and central-review based progression-free survival (CRb-PFS) in patients treated with imatinib and bevacizumab versus those treated with imatinib alone.

II. To compare the frequency and severity of toxicities associated with imatinib plus bevacizumab versus imatinib alone.

TERTIARY OBJECTIVES:

I. To explore the association between soluble vascular endothelial growth factor (VEGF), VEGF-factor D (VEGF-D), VEGF receptor (VEGFR)-1, VEGFR-2, angiopoietin-2 (Ang-2), platelet-derived growth factor receptor (PDGFR)-AA and PDGFR-BB levels, positron emission tomography (PET) imaging and immunohistochemistry for cyclin-dependent kinase inhibitor 2A (p16), VEGF and VEGFR, with kinase mutation status and clinical outcomes.

II. To explore imatinib pharmacokinetics with single nucleotide polymorphisms involving the adenosine triphosphate (ATP)-binding cassette, sub-family G (WHITE), member 2 (ABCG2) and cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) genes, as well as other genes that are reported to influence the absorption, distribution, metabolism and elimination of imatinib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (CLOSED TO ACCRUAL 10/1/2009): Patients receive imatinib mesylate orally (PO) once daily (QD) on days 1-21 and bevacizumab intravenously (IV) over 30-90 minutes on day 1.

ARM II (CLOSED TO ACCRUAL 10/1/2009): Patients receive imatinib mesylate PO QD on days 1-21.

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

After completion of study treatment, patients are followed at 1 month, every 6 months for 2 years, and then annually for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA-Vancouver Cancer Centre
• United States
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Summit Medical Center-Herrick Campus
    • Burlingame, California, United States, 94010
      • Mills - Peninsula Hospitals
    • Greenbrae, California, United States, 94904
      • Marin General Hospital
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Novato, California, United States, 94945
      • Sutter Cancer Research Consortium
    • San Francisco, California, United States, 94118
      • California Pacific Medical Center-Pacific Campus
    • Vallejo, California, United States, 94589
      • Sutter Solano Medical Center/Cancer Center
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20007
      • Medstar Georgetown University Hospital
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
    • Valdosta, Georgia, United States, 31603
      • South Georgia Medical Center
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush - Copley Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60631
      • Presence Resurrection Medical Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates Limited
    • La Grange, Illinois, United States, 60525
      • Adventist La Grange Memorial Hospital
    • Naperville, Illinois, United States, 60540
      • Edward Hospital/Cancer Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic-Urbana Main
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • Franciscan St. Francis Health-Beech Grove
    • Michigan City, Indiana, United States, 46360
      • Franciscan Saint Anthony Health-Michigan City
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic PC-William R Bliss Cancer Center
    • Clive, Iowa, United States, 50325
      • Medical Oncology and Hematology Associates-West Des Moines
    • Davenport, Iowa, United States, 52803
      • Genesis Medical Center - East Campus
    • Davenport, Iowa, United States, 52804
      • Genesis Medical Center - West Campus
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates-Laurel
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association CCOP
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas-Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas - Pratt
    • Salina, Kansas, United States, 67401
      • Salina Regional Health Center
    • Salina, Kansas, United States, 67401
      • Cancer Center of Kansas - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas - Wellington
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67208
      • Associates In Womens Health
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Main Office
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Wichita CCOP
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas - Winfield
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Bixby Medical Center
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Hospital
    • Ann Arbor, Michigan, United States, 48106
      • Michigan Cancer Research Consortium CCOP
    • Dearborn, Michigan, United States, 48124
      • Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48236
      • Saint John Hospital and Medical Center
    • Flint, Michigan, United States, 48502
      • Hurley Medical Center
    • Flint, Michigan, United States, 48532
      • Genesys Regional Medical Center-West Flint Campus
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
    • Livonia, Michigan, United States, 48154
      • Saint Mary Mercy Hospital
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Saint Joseph Mercy Port Huron
    • Saginaw, Michigan, United States, 48601
      • Saint Mary's of Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates PLLC
    • Southfield, Michigan, United States, 48075
      • Providence Hospital-Southfield Cancer Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Litchfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • Saint Joseph's Hospital - Healtheast
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Cancer Research for the Ozarks NCORP
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Montana
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Montana Cancer Consortium CCOP
    • Billings, Montana, United States, 59102
      • Frontier Cancer Center and Blood Institute-Billings
    • Billings, Montana, United States, 59107
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Berdeaux, Donald MD (UIA Investigator)
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • Saint Peter's Community Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59801
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Montana Cancer Specialists
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County
    • Voorhees, New Jersey, United States, 08043
      • Virtua West Jersey Hospital Voorhees
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Middletown, New York, United States, 10940
      • Orange Regional Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Rochester, New York, United States, 14620
      • Highland Hospital
    • Rochester, New York, United States, 14623
      • Interlakes Foundation Inc-Rochester
  • North Carolina
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists PA
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic
    • Bismarck, North Dakota, United States, 58501
      • Saint Alexius Medical Center
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Toledo Clinic Cancer Centers-Bowling Green
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Clyde, Ohio, United States, 43410
      • North Coast Cancer Care-Clyde
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Dayton, Ohio, United States, 45428
      • Veteran Affairs Medical Center
    • Elyria, Ohio, United States, 44035
      • Hematology Oncology Center Incorporated
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Toledo Clinic Cancer Centers-Maumee
    • Maumee, Ohio, United States, 43537
      • Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
    • Maumee, Ohio, United States, 43537
      • Saint Luke's Hospital
    • Oregon, Ohio, United States, 43616
      • Saint Charles Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic Cancer Centers-Oregon
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • Saint Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Toledo, Ohio, United States, 43614
      • University of Toledo
    • Toledo, Ohio, United States, 43617
      • Toledo Community Hospital Oncology Program CCOP
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital/Toledo Children's Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Saint Anne Hospital
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Wilmington, Ohio, United States, 45177
      • Clinton Memorial Hospital
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital
  • Oregon
    • Portland, Oregon, United States, 97216
      • Adventist Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Wilkes-Barre, Pennsylvania, United States, 18765
      • Geisinger South Wilkes-Barre
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Texas
    • San Antonio, Texas, United States, 78229
      • University Hospital
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78209
      • Audie L Murphy Veterans Affairs Hospital
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology Inc
  • Washington
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Bremerton, Washington, United States, 98310
      • Harrison HealthPartners Hematology and Oncology-Bremerton
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative-Seattle
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122
      • The Polyclinic
    • Seattle, Washington, United States, 98112
      • Group Health Cooperative of Puget Sound Oncology Consortium
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University Charleston
  • Wisconsin
    • Chippewa Falls, Wisconsin, United States, 54729
      • Marshfield Clinic-Chippewa Center
    • Eau Claire, Wisconsin, United States, 54701
      • Marshfield Clinic Cancer Center at Sacred Heart
    • Eau Claire, Wisconsin, United States, 54701
      • Sacred Heart Hospital
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Marshfield, Wisconsin, United States, 54449
      • Saint Joseph's Hospital
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • Rhinelander, Wisconsin, United States, 54501
      • Marshfield Clinic at James Beck Cancer Center
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Clinic-Rice Lake Center
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital
    • Wausau, Wisconsin, United States, 54401
      • Marshfield Clinic-Wausau Center
    • Weston, Wisconsin, United States, 54476
      • Diagnostic and Treatment Center
    • Weston, Wisconsin, United States, 54476
      • Marshfield Clinic - Weston Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Marshfield Clinic - Wisconsin Rapids Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• REGISTRATION # 1
• Patient must have a biopsy proven diagnosis of gastrointestinal stromal tumor (GIST) that is distantly metastatic or unresectable; patients must be determined to be unresectable for cure
• Patient may have measurable and/or non-measurable disease; computed tomography (CT) or magnetic resonance imaging (MRI) used for measurable disease must have been completed within 28 days prior to registration; CT or MRI used for non-measurable disease must have been completed within 42 days prior to registration; PET scans are not sufficient for disease assessment; all disease must be assessed and documented on the Baseline Tumor Assessment Form
• CT/MRI scans must be performed and submitted for central review; archived tissue must be submitted as outlined
• Institutions must seek additional patient consent for PET scans as outlined; if patient consents to the submission of PET scans, the patient must also be registered to Registration #2
• Patient must not have known brain metastasis
• Patient must have a Zubrod performance status of 0 - 3
• Patient must have resolution of transient toxicities from any prior chemotherapy, radiation therapy or surgery to =< grade 1 (Common Terminology Criteria for Adverse Events [CTCAE] version 3.0)
• Patient may have previously received traditional chemotherapeutic agents in any setting, provided at least 28 days have elapsed since completing chemotherapy and they have recovered to =< grade 1 from all drug-induced toxicities

• Patient must not have received prior treatment with bevacizumab or other agents targeting VEGF, VEGFR, or PDGFR for advanced disease; those agents may have been used in the adjuvant setting if the patient did not recur for at least 12 months following the completion of treatment; patients may be receiving imatinib for advanced disease prior to registration provided they meet ALL of the following criteria:

  • Patient must not have received more than 30 days of imatinib treatment prior to registration
  • Patients have not been restaged; (baseline disease assessments prior to initiation of imatinib must fulfill requirements)
  • Patients must have no clinical signs of progression
• Prior radiotherapy is allowed, provided at least 28 days have elapsed since the last treatment and there is evidence of progressive disease within the radiation field or disease outside the radiation field
• Patient must not have had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, or anticipation of need for major surgical procedure during the course of the study; no fine needle aspirations or core biopsies are allowed within 7 days prior to registration; no procedure to place a port-a-cath is allowed within 7 days prior to registration
• Patient must have a total bilirubin =< 2.0 x institutional upper limit of normal (IULN), obtained within 28 days prior to registration
• Patients without liver involvement must have serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 2.5 x IULN, obtained within 28 days prior to registration; patients with liver involvement must have SGOT or SGPT =< 5 x IULN
• Patient must have adequate renal function as defined by a serum creatinine =< 1.5 x IULN obtained within 28 days prior to registration
• Patient must have urine protein/creatinine ratio (UPC) < 1; this result must be obtained within 28 days prior to registration
• Patient must have an absolute neutrophil count (ANC) >= 1,000/mcl obtained within 28 days prior to registration
• Patient must have a platelet count >= 100,000/mcl obtained within 28 days prior to registration
• Patient must have hemoglobin >= 9 gm/dl (this may be achieved by transfusion if needed) obtained within 28 days prior to registration
• Patient must have an international normalized ratio (INR) =< 1.5, obtained within 28 days prior to registration
• Patient must have a partial thromboplastin time (PTT) =< IULN, obtained within 28 days prior to registration
• Patient must not be taking therapeutic doses of Coumadin (warfarin) as anticoagulation at the time of registration; patients requiring therapeutic anticoagulation may use low-molecular weight heparin (e.g., Lovenox) or other agents, and mini-dose Coumadin (1 mg PO QD) as prophylaxis is allowed
• Patient must not have had a cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction or unstable angina within 6 months prior to registration; patient must not have serious cardiac arrhythmia requiring medication, New York Heart Association (NYHA) class II or greater congestive heart failure, or clinically significant peripheral vascular disease
• Patient must not have had an abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to registration
• Patient must not plan to use other investigational agents while on protocol treatment
• Patient must have no contraindication to oral medications (e.g., severe dysphagia); patients with gastrostomy (G)- or jejunostomy (J)- tubes are eligible
• Patient must not have blood pressure > 160/90; patients with a history of hypertension must be on a stable regimen of anti-hypertensive therapy
• Patient must not have a serious, non-healing wound, ulcer, or bone fracture
• Patient must not be pregnant or nursing; male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout protocol treatment and for up to 6 months following discontinuation of study drugs
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
• If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day; in calculating days of tests and measurements, the day a test or measurement is done is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks later would be considered day 28
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
• At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
• REGISTRATION #2 - PET SUBSTUDY:
• Patient must have been registered to the main study
• Patient must have consented to the submission of PET scans

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (CLOSED TO ACCRUAL 10/1/2009) (imatinib and bevacizumab); Patients receive imatinib mesylate PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: Bevacizumab; Given IV; Other Names: Avastin; Anti-VEGF; Anti-VEGF Humanized Monoclonal Antibody; Anti-VEGF rhuMAb; Bevacizumab Biosimilar BEVZ92; Bevacizumab Biosimilar BI 695502; Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer; Recombinant Humanized Anti-VEGF Monoclonal Antibody; rhuMab-VEGF; Drug: Imatinib Mesylate; Given PO; Other Names: Gleevec; CGP 57148; CGP57148B; Glivec; STI 571; STI-571; STI571
Active Comparator: Arm II (CLOSED TO ACCRUAL 10/1/2009) (imatinib); Patients receive imatinib mesylate PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Drug: Imatinib Mesylate; Given PO; Other Names: Gleevec; CGP 57148; CGP57148B; Glivec; STI 571; STI-571; STI571

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	From date of registration (defined as date of randomization) to date of first observation of progressive disease, death due to any cause or symptomatic deterioration. Patients last known to be alive and progression free are censored at last date of contact. Progression is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy), provided at least one target lesion does NOT demonstrate uniform hypoattenuation over > 90% of maximal cross sectional area; unequivocal progression of non-measurable disease; appearance of new lesion/site that is not uniformly hypoattenuating; a hyperattenuating region within a previously cystic/uniformly hypoattenuating lesion will be considered progressive disease if hyperattenuating region is either >= 1 cm in longest diameter or round/oval and forms acute margins with border of target lesion; death due to disease.	Up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.	Up to 7 years
Overall Survival	From date of registration (defined as date of randomization) to date of death due to any cause. Patients last known to be alive are censored at last date of contact. Note: median was not reached in the Imatinib arm due to limited follow-up data.	up to 7 years
Central-review Based Progression-free Survival (CRb-PFS)	From date of registration (defined as date of randomization) to date of first documentation of one of the following events: death; first documentation of progression based on central review of the appropriate computed tomography (CT) or magnetic resonance imaging (MRI) scans; development of new lesions or disease not identified on CT or MRI; or symptomatic deterioration. Patients not experiencing any of these events will be censored at last date of contact.	up to 7 years
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 7 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Charles Blanke, Southwest Oncology Group

Publications and helpful links

General Publications

• Blanke CD, Rankin C, Corless C, Eary JF, Mulder K, Okuno SH, George S, Heinrich M. S0502: A SWOG Phase III Randomized Study of Imatinib, With or Without Bevacizumab, in Patients With Untreated Metastatic or Unresectable Gastrointestinal Stromal Tumors. Oncologist. 2015 Dec;20(12):1353-4. doi: 10.1634/theoncologist.2015-0295. Epub 2015 Nov 17.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: May 10, 2006
• First Submitted That Met QC Criteria: May 10, 2006
• First Posted (Estimate): May 11, 2006

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Antibodies; Immunoglobulins; Bevacizumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Imatinib Mesylate; Immunoglobulin G; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00776 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA032102 (U.S. NIH Grant/Contract); U10CA180888 (U.S. NIH Grant/Contract); CDR0000482236; S0502 (CTEP)