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

Genentech

Status and phase

Completed

Phase 2

Conditions

Glioblastoma

Treatments

Drug: bevacizumab

Drug: irinotecan

Study type

Interventional

Funder types

Industry

Identifiers

NCT00345163

AVF3708g

Details and patient eligibility

About

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).

Enrollment

167 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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