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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: bevacizumab
* Drug: irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>|
| Experimental: 2<br> | Drug: bevacizumab<br>* Intravenous repeating dose<br>Drug: irinotecan<br>* Intravenous repeating dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response, as determined by the independent review facility (IRF) |  | Complete response or partial response, determined on two consecutive assessments ≥4 weeks apart | 
| Progression-free survival, as determined by the IRF |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and serious adverse events |  | Length of patient on study | 
| Duration of objective response, as determined by the IRF |  | Complete or partial response determined on two consecutive assessments ≥4 weeks apart | 
| Overall survival |  | Time from randomization to death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Glioblastoma Multiforme, Avastin, Brain Cancer, GBM