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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00345163
• Date of registration: 23/06/2006
• Primary sponsor: Genentech
• Public title: A Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN) BRAIN
• Scientific title: A Phase II, Multicenter, Randomized, Non-Comparative Clinical Trial to Evaluate the Efficacy and Safety of Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme in First or Second Relapse
• Date of first enrolment: July 2006
• Target sample size: 167
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00345163
• Study type: Interventional
• Study design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Jane Huang, M.D.
• Affiliation: Genentech

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Glioblastoma

Intervention(s)

Drug: bevacizumab

Drug: irinotecan

Primary Outcome(s)

Objective response, as determined by the independent review facility (IRF) [Time Frame: Complete response or partial response, determined on two consecutive assessments =4 weeks apart]

Progression-free survival, as determined by the IRF [Time Frame: 6 months]

Secondary Outcome(s)

Duration of objective response, as determined by the IRF [Time Frame: Complete or partial response determined on two consecutive assessments =4 weeks apart]

Incidence of adverse events and serious adverse events [Time Frame: Length of patient on study]

Overall survival [Time Frame: Time from randomization to death]

Secondary ID(s)

AVF3708g

Source(s) of Monetary Support

Please refer to primary and secondary sponsors