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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, United States
Mills - Peninsula Hospitals
Burlingame, California, United States
Marin General Hospital
Greenbrae, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Sutter Cancer Research Consortium
Novato, California, United States
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.
Time frame: Up to 7 years
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 7 years
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California Pacific Medical Center-Pacific Campus
San Francisco, California, United States
Sutter Solano Medical Center/Cancer Center
Vallejo, California, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
John B Amos Cancer Center
Columbus, Georgia, United States
Memorial University Medical Center
Savannah, Georgia, United States
...and 182 more locations