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Phase III Randomized Study of Imatinib Mesylate With Versus Without Bevacizumab in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumor
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 | Protocol IDs |
|---|
| Phase III | Biomarker/Laboratory analysis, Treatment | Closed | 18 and over | SWOG-S0502
S0502, CALGB-S0502, CAN-NCIC-S0502, NCT00324987 |
Special Category:
NCI - CMS pilot project trial, NCI Web site featured trial, CTSU trial Objectives - Compare the progression-free survival of patients with metastatic or unresectable gastrointestinal stromal tumor treated with imatinib mesylate with vs without bevacizumab.
- Compare the response probabilities (in patients with measurable disease) and overall survival rates in patients treated with these regimens.
- Compare the frequency and severity of toxicities associated with these regimens in these patients.
- 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.
- 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 by MRI or CT scan
- 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 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
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)
- 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 572A total of 572 patients will be accrued for this study. Outcomes Primary Outcome(s)Progression-free survival as measured by Cox Proportional Hazards Model at 6 months
Secondary Outcome(s)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. [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.
Trial Contact Information
Trial Lead Organizations Southwest Oncology Group | | | | Charles Blanke, MD, FACP, Protocol chair | | | | | Margaret von Mehren, MD, Protocol co-chair | | | Ph: 215-728-3545; 888-369-2427 |
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Cancer and Leukemia Group B | | | | George Demetri, MD, Protocol chair | | | |
NCIC-Clinical Trials Group | | | | Vivien Bramwell, MB, BS, PhD, FRCP, Protocol chair | | | |
Related Information Featured trial article
| Registry Information | | | Official Title | | A Phase III Randomized Study of Imatinib, With or Without Bevacizumab (NSC-704865), in Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors | | | Trial Start Date | | 2008-04-15 | | | Trial Completion Date | | 2014-04-30 (estimated) | | | Registered in ClinicalTrials.gov | | NCT00324987 | | | Date Submitted to PDQ | | 2006-04-18 | | | Information Last Verified | | 2009-09-23 | | | NCI Grant/Contract Number | | CA32102 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.  Back to Top |
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