Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma

• Status: Completed
• Trial end date: 2013-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective To estimate 6-month progression free survival probability of patients with recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs.

Secondary Objectives To evaluate safety & tolerability of bortezomib plus Avastin among patients with recurrent malignant glioma.

To evaluate radiographic response, progression free survival & overall survival of patients with recurrent malignant glioma treated with bortezomib plus Avastin

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

Details

• Lead Sponsor: Duke University
• Collaborators: Genentech, Inc.; Millennium Pharmaceuticals, Inc.
• Treatments: Bevacizumab; Bortezomib

Criteria

Inclusion Criteria:

Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV malignant glioma (MG)

• Age >18 yrs

• No prior treatment with bortezomib, & no Avastin in last 3 months, not allowed to have progressed to Avastin regimen. No history of > or equal to grade 2 CNS hemorrhage or grade 3 or higher toxicities while on Avastin

• At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy & enrollment in this study

• Karnofsky Performance Status (KPS) > or equal to 70%

• Hemoglobin (Hgb) > or = to 9 g/deciliter (dL), absolute neutrophil count (ANC) > or = to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter;

• Serum creatinine <1.5 mg/dL, serum glutamic oxalocetic transaminase (SGOT) & bilirubin <1.5 x upper limit of normal

• Signed informed consent approved by IRB;

• If sexually active, patients must agree to take contraceptive measures for duration of treatments

• May have had up to 3 biological therapies (such as tyrosine kinase inhibitors, topoisomerase I or II inhibitors, or rapamycin)

Exclusion Criteria:

• Gr 2 or greater peripheral neuropathy at time of study enrollment

• No prior taxanes, as it predisposes to sensory neuropathy

• Co-medication that may interfere with study results, e.g. immuno-suppressive agents other than corticosteroids

• Greater than 3 prior recurrences

• Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months)

• History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months

• Requires therapeutic anti-coagulation

• At least 4 weeks from Day 0 of prior monthly chemotherapy (at least 6 weeks if a nitrosourea). At least 1 week from last dose of daily chemotherapy (such as metronomic temozolomide, cytoxan) or targeted therapies administered daily (such as gleevec, tarceva)

• Pregnancy or breast feeding

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state

• Patients with another primary malignancy that has required treatment within past year.

Avastin-Specific Concerns:

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• Systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg

• Unstable angina

• New York Heart Association Gr II or > congestive heart failure

• History of myocardial infarction within 6 months

• History of stroke within 6 months

• Clinically significant peripheral vascular disease

• Evidence of bleeding diathesis, coagulopathy as documented by an elevated prothrombin time (PT), partial thromboplastin time (PTT)/bleeding time

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during course of study

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0

• Urine protein: creatinine ratio > or = to 1.0 at screening

• History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 0

• Serious, non-healing wound, ulcer, or bone fracture

• Known hypersensitivity to any component of Avastin

• Inability to comply with study and/or follow-up procedures