NCT00324987

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

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

• Status: Terminated
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

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.

Conditions

• Gastrointestinal Stromal Tumor

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
DRUG	Imatinib Mesylate	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2008-04-01
• Primary completion: 2015-07-01
• Completion: 2015-07-01
• First posted: 2006-05-11
• Last updated: 2017-09-14
• Results posted: 2017-09-14

Locations

192 sites across 2 countries: United States, Canada