Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas

• Status: Completed
• Trial end date: 2013-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection.

Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

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

Details

• Lead Sponsor: Duke University
• Collaborators: Genentech, Inc.; Schering-Plough
• Treatments: Bevacizumab; Camptothecin; Dacarbazine; Irinotecan; Temozolomide

Criteria

Inclusion Criteria:

• Patients must have histologically confirmed diagnosis of World Health Organization (WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 4 weeks of the last major surgical procedure.

• Age > 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 ≥ 60 percent.

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

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

• For patients on corticosteroids, they must be on a stable or decreasing dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible.

• Signed informed consent approved by the Institutional Review Board

• No evidence of > grade 1 central nervous system (CNS) hemorrhage on the baseline MRI or CT scan.

• If sexually active, patients will take contraceptive measures for the duration of treatment 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 intravenous (IV) antibiotics.

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

• Evidence of > grade 1 CNS hemorrhage on baseline MRI on CT scan.

Avastin-Specific Concerns:

Subjects meeting any of the following criteria are ineligible for study entry:

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

• Blood pressure of 150/100 mmHg

• Unstable angina

• New York Heart Association (NYHA) Grade II or greater 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 (prothrombin time (PT) or partial thromboplastin time (PTT) >1.5x normal or a history of > three grade 2 or greater hemorrhages)

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first Avastin infusion during XRT/Temodar or anticipation of need for major surgical procedure during the course of the study

• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to first Avastin infusion during XRT/Temodar

• Pregnant (positive pregnancy test) or lactating

• Urine protein >1.0 + at screening

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to first Avastin infusion during XRT/Temodar

• Serious, non-healing wound, ulcer, or bone fractures.

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