Bi-weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

• Status: Completed
• Trial end date: 2014-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective - to determine the 6-month progression free survival (PFS) of adult patients with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus (Avastin) bevacizumab.

Secondary objectives - to determine radiographic response including specialized MRI sequences, safety and overall survival of adult patients with with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus bevacizumab (Avastin). Additionally, tumor DNA (MGMT) analysis as it relates to survival will be evaluated.

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

Details

• Lead Sponsor: Center for Neurosciences, Tucson
• Collaborator: Genentech, Inc.
• Treatments: Bevacizumab; Dacarbazine; Temozolomide

Criteria

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of a glioblastoma multiforme/gliosarcoma and:

• Must have completed at least 2 cycles of adjuvant chemotherapy

• Age > 18 years

• Karnofsky > 60%

• Hematocrit > 29%, ANC > 1,500 cells/dl, platelets > 125,000 cells/dl

• Serum creatinine < 1.5 mg/dl, BUN < 25 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal

• If on corticosteroids, must be on a stable dose for 1 week prior to entry; if clinically possible, the dose should not be escalated over entry dose level

• Signed informed consent approved by the Institutional Review Board prior to study entry

• If sexually active, will take contraceptive measures for the duration of the treatments

Exclusion Criteria:

• Prior toxicity grade ≥ 3 with TMZ

• Prior treatment with bevacizumab

• Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control

• Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study

• Acute or chronic liver disease (i.e., hepatitis, cirrhosis)

• Confirmed diagnosis of HIV infection

• Have received investigational drugs less than 4 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy

• Have received chemotherapy within 2 weeks prior (6 weeks for nitrosourea) to entry on this study, or who have not recovered from the toxic effects of such therapy

• Have received biologic, immunotherapeutic or cytostatic agents within 1 week prior to entry on this study or who have not recovered from the toxic effects of such therapy

• Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant

• Have received radiation therapy within 2 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy.

• Surgical resection of brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy

• Have had any surgery other than resection of a brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy

• Unwilling to or unable to comply with the protocol

• Evidence of tumor progression within on immediate post radiation brain imaging

• Have not received at least 2 cycles of adjuvant chemotherapy

• Life expectancy of less than 12 weeks

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

Bevacizumab-Specific Exclusions:

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)

• Prior history of hypertensive crisis or hypertensive encephalopathy

• New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)

• History of myocardial infarction or unstable angina within 6 months

• History of stroke or transient ischemic attack within 6 months

• Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months

• Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days

• History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

• Serious, non-healing wound, active ulcer, or untreated bone fracture.

• Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening

• Known hypersensitivity to any component of bevacizumab