Clinical Trial Finder

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

Arms

Experimental: 1

Experimental: 2

Interventions

Drug: - bevacizumab

Intravenous repeating dose

Drug: - irinotecan

Intravenous repeating dose