Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase III trial is studying imatinib mesylate and bevacizumab to see how well they work compared to imatinib mesylate alone in treating patients with metastatic or unresectable gastrointestinal stromal tumor. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving imatinib mesylate together with bevacizumab may kill more tumor cells. It is not yet known whether imatinib mesylate and bevacizumab are more effective than imatinib mesylate alone in treating gastrointestinal stromal tumor.

Further Study Information

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.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Charles Blanke

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00324987
Information obtained from ClinicalTrials.gov on March 26, 2013