A Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN)

• Status: Completed
• Trial end date: 2007-09-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Bevacizumab; Camptothecin; Irinotecan

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