Expired Study
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Durham, North Carolina 27710


Purpose:

Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan. Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan. To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.


Study summary:

The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high MGMT, conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal IGG 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed GBM patients, including a RTOG study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a UCLA study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.


Criteria:

Inclusion Criteria: - Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 4 weeks of the last major surgical procedure. - Age > 18 years. - An interval of at least 2 weeks and not > 6 weeks between prior major surgical procedure and study enrollment. - No prior radiotherapy or chemotherapy for a brain tumor - Karnofsky ≥ 60 percent. - Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/ microliter l, platelets ≥ 125,000 cells/microliter l. - Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times ULN. - For patients on corticosteroids, they must be on a stable or decreasing dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible. - Signed informed consent approved by the Institutional Review Board - No evidence of > grade 1 CNS hemorrhage on the baseline MRI or CT scan. - If sexually active, patients will take contraceptive measures for the duration of treatment as stated in the informed consent. Exclusion Criteria: - Pregnancy or breast feeding. - Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids. - Active infection requiring IV antibiotics. - Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor. - Evidence of > grade 1 CNS hemorrhage on baseline MRI on CT scan. Avastin-Specific Concerns: Subjects meeting any of the following criteria are ineligible for study entry: - Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study - Blood pressure of 150/100 mmHg - Unstable angina - New York Heart Association (NYHA) Grade II or greater congestive heart failure - History of myocardial infarction within 6 months - History of stroke within 6 months - Clinically significant peripheral vascular disease - Evidence of bleeding diathesis - Coagulopathy (PT or PTT >1.5x normal or a history of > three grade 2 or greater hemorrhages) - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first Avastin infusion during XRT/Temodar or anticipation of need for major surgical procedure during the course of the study - Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to first Avastin infusion during XRT/Temodar - Pregnant (positive pregnancy test) or lactating - Urine protein >1.0 + at screening - History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to first Avastin infusion during XRT/Temodar - Serious, non-healing wound, ulcer, or bone fractures. - Inability to comply with study and/or follow-up procedures.


NCT ID:

NCT00597402


Primary Contact:

Principal Investigator
James J Vredenburgh, MD
Duke University Health System


Backup Contact:

N/A


Location Contact:

Durham, North Carolina 27710
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: March 16, 2018

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