Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.

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

Details

• Lead Sponsor: Duke University
• Collaborators: Genentech, Inc.; GlaxoSmithKline
• Treatments: Bevacizumab; Dacarbazine; Temozolomide; Topotecan

Criteria

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 6 weeks of the last major surgical procedure.

• Age > or = to 18 years.

• An interval of at least 2 weeks and not > 6 weeks between prior major surgical procedure and study enrollment.

• No prior radiotherapy or chemotherapy for a brain tumor

• Karnofsky > or = to 60%.

• Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/microliter, platelets ≥ 125,000 cells/microliter.

• Serum creatinine ≤ 1.5 mg/dl, serum glutamic oxaloacetic transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal.

• Signed informed consent approved by the Institutional Review Board

• If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards as stated in the informed consent.

Exclusion Criteria:

• Pregnancy or breast feeding.

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

• Active infection requiring IV antibiotics.

• Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.

• Evidence of > grade 1 central nervous system (CNS) hemorrhage on baseline MRI on CT scan.

Avastin-specific Exclusion Criteria:

• Inadequately controlled hypertension (defined as systolic blood pressure > 150 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

• History of myocardial infarction or unstable angina within 6 months prior to study enrollment

• History of stroke or transient ischemic attack within 6 months prior to study enrollment

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

• History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to study enrollment

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

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment 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 prior to study enrollment

• History of abdominal fistula, gastrointestinal perforation within 6 months prior to study enrollment

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

• Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

• Known hypersensitivity to any component of Avastin

• Pregnant (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential