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

Center for Neurosciences, Tucson

Status and phase

Completed

Phase 2

Conditions

Recurrent Glioblastoma Multiforme

Recurrent Gliosarcoma

Treatments

Drug: temozolomide and bevacizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00883298

AVF4514s

Details and patient eligibility

About

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.

Full description

This is a phase II study of the combination of Avastin and temozolomide for patients with recurrent glioblastoma multiforme. Avastin is administered intravenously at a dose of 10 mg/kg on days 1 and 15 every 28 days and temozolomide is administered at a dose of 100 mg/m2 on days 1-5 and 15-19 every 28 days (one cycle). Patients will have a baseline MRI, an MRI scan after the first cycle and every other cycle after that. If there is no evidence of disease progression or unacceptable toxicity, patients will receive one year of therapy. If there is evidence of added benefit (eg: tumor regression), patients can stay on treatment longer than one year, per investigator discretion.

Enrollment

30 patients

Sex

All

Ages

18 to 83 years old

Volunteers

No Healthy Volunteers

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