a study to evaluate bevacizumab alone or in combination with irinotecan for treatment of glioblastoma multiforme (brain)

Conditions: Glioblastoma

Summary: this is a phase ii, open-label, multicenter, randomized, non comparative study consisting of two concurrent single-arms. approximately 160 subjects will be randomized in a 1:1 ratio to arm 1 (bevacizumab alone) or arm 2 (bevacizumab + irinotecan).


Eligibility criteria:
inclusion criteria: * signed informed consent form * age ≥ 18 years * histologically confirmed gbm in first or second relapse * radiographic demonstration of disease progression following prior therapy * bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on mri performed within 14 days prior to first treatment (day 0) * an interval of ≥ 4 weeks since prior surgical resection * prior standard radiation for gbm * prior chemotherapy: first-relapse subjects * prior chemotherapy: second-relapse subjects * recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for mri changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation mri, develops that is outside the primary radiation field * prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field * karnofsky performance status ≥ 70 * life expectancy \> 12 weeks * use of an effective means of contraception in males and in females of childbearing potential * ability to comply with study and follow-up procedures exclusion criteria: * prior treatment with irinotecan, bevacizumab, or another vegf or vegfr-targeted agent * prior treatment with prolifeprospan 20 with carmustine wafer * prior intracerebral agents * need for urgent palliative intervention for primary disease (e.g., impending herniation) * evidence of recent hemorrhage on baseline mri of the brain with the following exceptions: presence of hemosiderin; resolving hemorrhagic changes related to surgery; presence of punctate hemorrhage in the tumor * received more than two treatment regimens for grade iii and/or grade iv glioma * blood pressure of \> 150 mmhg systolic and \> 100 mmhg diastolic * history of hypertensive encephalopathy * new york heart association (nyha) grade ii or greater chf * history of myocardial infarction or unstable angina within 6 months prior to day 0 * history of stroke or transient ischemic attack within 6 months prior to study enrollment * significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to day 0 * evidence of bleeding diathesis or coagulopathy * history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0 * history of intracerebral abscess within 6 months prior to day 0 * major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0, anticipation of need for major surgical procedure during the course of the study * minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to day 0 * serious non-healing wound, ulcer, or bone fracture * pregnancy (positive pregnancy test) or lactation * known hypersensitivity to any component of bevacizumab * history of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix) * pregnant or nursing females * unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication * subjects unable to undergo an mri with contrast

Keywords: glioblastoma multiforme avastin brain cancer gbm