Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Biomarker/Laboratory analysis, Treatment Active 18 and over NCI SWOG-S0502 S0502, CALGB-S0502, CAN-NCIC-S0502, NCT00324987

Special Category: NCI - CMS pilot project trial, NCI Web site featured trial, CTSU trial

Objectives

1. Compare the progression-free survival of patients with metastatic or unresectable gastrointestinal stromal tumor treated with imatinib mesylate with vs without bevacizumab.
2. Compare the response probabilities (in patients with measurable disease) and overall survival rates in patients treated with these regimens.
3. Compare the frequency and severity of toxicities associated with these regimens in these patients.
4. 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.
5. 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.

Entry Criteria

Disease Characteristics:

• Histologically confirmed gastrointestinal stromal tumor (GIST)
  • Metastatic or unresectable disease
    • Determined to be unresectable for cure



• Measurable and/or nonmeasurable disease



• No known brain metastasis

Prior/Concurrent Therapy:

• 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 imatinib mesylate, bevacizumab, or other agents targeting KIT, 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

Patient Characteristics:

• Zubrod performance status 0-3
• Platelet count ≥ 100,000/mm³
• Absolute neutrophil count ≥ 1,000/mm³
• 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)
• Creatinine ≤ 1.5 times ULN
• Urine protein:creatinine ratio < 1
• INR ≤ 1.5
• PTT normal
• 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

Expected Enrollment

A total of 572 patients will be accrued for this study.

Outcomes

Progression-free survival as measured by Cox Proportional Hazards Model at 6 months

Overall survival as measured by Cox Proportional Hazards Model
Response probabilities in subset of patients with measurable disease
Frequency and severity of toxicities as measured by NCI CTCAE v3.0
Correlation between growth factor/receptor levels, positron-emission tomography imaging, and immunohistochemistry for p16, VEGF, and VEGFR with kinase mutation status and clinical outcomes
Pharmacokinetics 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.

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

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Charles Blanke, MD, FACP, Protocol chair		Ph: 604-877-6098 ext. 2738 Email: cblanke@bccancer.bc.ca
Margaret von Mehren, MD, Protocol co-chair		Ph: 215-728-3545; 888-369-2427

Cancer and Leukemia Group B

George Demetri, MD, Protocol chair		Ph: 617-632-3985; 866-790-4500 Email: gdemetri@partners.org

NCIC-Clinical Trials Group

Vivien Bramwell, MB, BS, PhD, FRCP, Protocol chair		Ph: 403-521-3707

U.S.A.
Alabama
	Mobile
	Providence Cancer Center at Providence Hospital
		Paul Schwarzenberger, MD	Ph:  251-435-5892
California
	Los Angeles
	USC/Norris Comprehensive Cancer Center and Hospital
		Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital	Ph:  323-865-0451
Illinois
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Decatur
	Decatur Memorial Hospital Cancer Care Institute
		Clinical Trials Office - Decatur Memorial Hospital Cancer Care Institute	Ph:  217-876-6601
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3010
	Springfield
	Regional Cancer Center at Memorial Medical Center
		Clinical Trials Office - Regional Cancer Center at Memorial Medical Center	Ph:  217-788-4233
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard Gross, MD	Ph:  317-787-3311
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3010
	Richmond
	Reid Hospital & Health Care Services
		Howard Gross, MD	Ph:  765-983-3000
Iowa
	Ames
	McFarland Clinic, PC
		Clinical Trials Office - McFarland Clinic, PC	Ph:  515-239-2621
	Des Moines
	CCOP - Iowa Oncology Research Association
		Roscoe Morton, MD, FACP	Ph:  515-244-7586
	John Stoddard Cancer Center at Iowa Lutheran Hospital
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Lutheran Hospital	Ph:  515-241-8704
	John Stoddard Cancer Center at Iowa Methodist Medical Center
		Clinical Trials Office - John Stoddard Cancer Center at Iowa Methodist Medical Center	Ph:  515-241-6727
	Medical Oncology and Hematology Associates at John Stoddard Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-244-7586
	Medical Oncology and Hematology Associates at Mercy Cancer Center
		Roscoe Morton, MD, FACP	Ph:  515-244-7586
	Mercy Cancer Center at Mercy Medical Center - Des Moines
		Roscoe Morton, MD, FACP	Ph:  515-244-7586
	Mercy Capitol Hospital
		Roscoe Morton, MD, FACP	Ph:  515-244-7586
Kansas
	Chanute
	Cancer Center of Kansas, PA - Chanute
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Dodge City
	Cancer Center of Kansas, PA - Dodge City
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	El Dorado
	Cancer Center of Kansas, PA - El Dorado
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Independence
	Cancer Center of Kansas-Independence
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Kingman
	Cancer Center of Kansas, PA - Kingman
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Liberal
	Southwest Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Newton
	Cancer Center of Kansas, PA - Newton
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Parsons
	Cancer Center of Kansas, PA - Parsons
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Pratt
	Cancer Center of Kansas, PA - Pratt
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Salina
	Cancer Center of Kansas, PA - Salina
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wellington
	Cancer Center of Kansas, PA - Wellington
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wichita
	Associates in Womens Health, PA - North Review
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Medical Arts Tower
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	CCOP - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Via Christi Cancer Center at Via Christi Regional Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Winfield
	Cancer Center of Kansas, PA - Winfield
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
Michigan
	Adrian
	Hickman Cancer Center at Bixby Medical Center
		Clinical Trials Office - Hickman Cancer Center at Bixby Medical Center	Ph:  517-265-0116
	Kalamazoo
	Borgess Medical Center
		Raymond Lord, MD	Ph:  269-373-7488
	Bronson Methodist Hospital
		Raymond Lord, MD	Ph:  269-373-7488
	West Michigan Cancer Center
		Clinical Trials Office - West Michigan Cancer Center	Ph:  269-373-7458
	Lambertville
	Haematology-Oncology Associates of Ohio and Michigan, PC
		Paul Schaefer, MD	Ph:  419-843-6147
	Monroe
	Mercy Memorial Hospital - Monroe
		Paul Schaefer, MD	Ph:  419-843-6147
	Saint Joseph
	Oncology Care Associates, PLLC
		Eric Lester, MD	Ph:  269-985-0029
	Southfield
	Providence Cancer Institute at Providence Hospital - Southfield Campus
		Anibal Drelichman, MD, MPH, FACP	Ph:  248-849-3541 800-341-0801
Minnesota
	Burnsville
	Fairview Ridges Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Coon Rapids
	Mercy and Unity Cancer Center at Mercy Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Edina
	Fairview Southdale Hospital
		Clinical Trials Office - Fairview Southdale Hospital	Ph:  612-625-3650
	Fridley
	Mercy and Unity Cancer Center at Unity Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Hutchinson
	Hutchinson Area Health Care
		Daniel Anderson	Ph:  320-234-5000 800-454-3903
	Lichfield
	Meeker County Memorial Hospital
		Clinical Trials Office - Meeker County Memorial Hospital	Ph:  320-693-4520
	Maplewood
	HealthEast Cancer Care at St. John's Hospital
		Daniel Anderson	Ph:  651-232-7970
	Minnesota Oncology Hematology, PA - Maplewood
		Patrick Flynn, MD	Ph:  612-863-8585
	Minneapolis
	Hennepin County Medical Center - Minneapolis
		Clinical Trials Office - Hennepin County Medical Center - Minneapolis	Ph:  612-873-5911
	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
		Clinical Trials Office - Virginia Piper Cancer Institute	Ph:  612-863-5654
	Robbinsdale
	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
		Clinical Trials Office - Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Ph:  763-520-1893
	Saint Louis Park
	CCOP - Metro-Minnesota
		Patrick Flynn, MD	Ph:  612-863-8585
	Park Nicollet Cancer Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Saint Paul
	HealthEast Cancer Care at St. Joseph's Hospital
		Daniel Anderson	Ph:  651-232-7970
	United Hospital
		Patrick Flynn, MD	Ph:  612-863-8585
	Shakopee
	St. Francis Cancer Center at St. Francis Medical Center
		Daniel Anderson	Ph:  952-403-2031
	St. Paul
	Regions Hospital Cancer Care Center
		Clinical Trials Office - Regions Hospital Cancer Care Center	Ph:  651-254-1517
	Waconia
	Ridgeview Medical Center
		Patrick Flynn, MD	Ph:  612-863-8585
	Woodbury
	HealthEast Cancer Care at Woodwinds Health Campus
		Daniel Anderson	Ph:  651-232-7970
	Minnesota Oncology Hematology, PA - Woodbury
		Patrick Flynn, MD	Ph:  612-863-8585
Missouri
	Springfield
	CCOP - Cancer Research for the Ozarks
		John Goodwin, MD	Ph:  417-889-8099
	St. John's Regional Health Center
		John Goodwin, MD	Ph:  417-889-8099
Montana
	Billings
	Billings Clinic - Downtown
		Clinical Trials Office - Billings Clinic - Downtown	Ph:  800-996-2663
			Email: research@billingsclinic.org
	CCOP - Montana Cancer Consortium
		Benjamin Marchello, MD	Ph:  406-259-2245 800-361-3239
	Hematology-Oncology Centers of the Northern Rockies - Billings
		Benjamin Marchello, MD	Ph:  406-238-6290 800-648-6274
	Northern Rockies Radiation Oncology Center
		Benjamin Marchello, MD	Ph:  406-248-2212 800-358-8818
	St. Vincent Healthcare Cancer Care Services
		Benjamin Marchello, MD	Ph:  406-657-7000
	Bozeman
	Bozeman Deaconess Cancer Center
		Benjamin Marchello, MD	Ph:  406-585-5070
	Butte
	St. James Healthcare Cancer Care
		Benjamin Marchello, MD	Ph:  406-723-2500
	Great Falls
		Benjamin Marchello, MD
	Great Falls Clinic - Main Facility
		Benjamin Marchello, MD	Ph:  406-454-2171 800-421-1649
	Havre
	Northern Montana Hospital
		Benjamin Marchello, MD	Ph:  406-265-2211 800-352-5097
	Helena
	St. Peter's Hospital
		Benjamin Marchello, MD	Ph:  406-442-2480
	Kalispell
	Glacier Oncology, PLLC
		Benjamin Marchello, MD	Ph:  406-752-7600
	Kalispell Medical Oncology at KRMC
		Benjamin Marchello, MD	Ph:  406-752-8900
	Kalispell Regional Medical Center
		Benjamin Marchello, MD	Ph:  406-752-5111
	Missoula
	Community Medical Center
		Benjamin Marchello, MD	Ph:  406-728-4100
	Guardian Oncology and Center for Wellness
		Benjamin Marchello, MD	Ph:  406-721-1118
	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
		Clinical Trials Office - Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Ph:  406-329-7029
	Montana Cancer Specialists at Montana Cancer Center
		Clinical Trials Office - Montana Cancer Specialists at Montana Cancer Center	Ph:  406-238-6962
New Jersey
	Marlton
	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
		Clinical Trials Office - Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Ph:  888-847-8823
	Voorhees
	Fox Chase Virtua Health Cancer Program at Virtua West Jersey
		Michael Entmacher, MD