Clinical Trial Finder

Inclusion Criteria:

• - Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma.

• - Prior histologic diagnosis of low-grade glioma allowed provided it has been upgraded to GBM after repeat resection.

• - Has undergone surgery to collect tumor tissue 3-6 weeks ago.

• - Measurable or assessable disease is not required.

• - Karnofsky performance status 60-100% - Life expectancy > 8 weeks.

• - White Blood Cell (WBC) ≥ 3,000/mm³ - Absolute Neutrophil Count (ANC) ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Hemoglobin ≥ 10 g/dL (transfusion allowed) - Serum Glutamate Oxaloacetate Transaminase (SGOT) < 2.5 times upper limit of normal (ULN) - Bilirubin < 2.5 times ULN.

• - INR (international normalized ratio) ≤ 1.5 times ULN (except if on therapeutic anticoagulation therapy) - aPTT (activated partial thromboplastin time) ≤ 1.5 times ULN (except if on therapeutic anticoagulation therapy) - Creatinine < 1.5 mg/dL.

• - Urine protein:creatinine ratio < 1.0.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

• - More than 28 days since prior major surgical procedures or open biopsy (other than craniotomy) - More than 7 days since prior minor surgical procedures (e.g., placement of PortoCath (port-a-cath - a port placed under the subjects skin), stereotactic biopsy, fine-needle aspirations, or core biopsies) - More than 4 weeks since prior and no concurrent participation in another experimental drug study.

• - Prior or concurrent corticosteroids, anti-epileptic drugs, analgesics, or other drugs to treat symptoms or prevent complications are allowed.

• - Concurrent full-dose warfarin or its equivalent (i.e., unfractionated and/or low molecular weight heparin) allowed.

Exclusion Criteria:

• - unstable angina.

• - BP > 150/100 mm Hg.

• - New York Heart Association (NYHA) class II-IV congestive heart failure.

• - myocardial infarction within the past 6 months.

• - stroke within the past 6 months.

• - clinically significant peripheral vascular disease.

• - evidence of bleeding diathesis or coagulopathy.

• - intracerebral abscess within past 6 months.

• - abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months.

• - serious, non-healing wound, ulcer, or bone fracture.

• - Any wound requiring surgical intervention (including scalp wounds requiring cranioplasty) allowed provided the wound is clean and without further infection post-surgical intervention.

• - significant traumatic injury within the past 28 days.

• - concurrent serious uncontrolled medical illness including, but not limited to, the following: - Ongoing or active infection requiring IV antibiotics.

• - Psychiatric illness/social situation that would limit compliance with study requirements.

• - Disorders associated with significant immunocompromised state (e.g., HIV, systemic lupus erythematosus) - other cancer within the past 3 years, except nonmelanoma skin cancer or carcinoma in situ of the cervix.

• - disease that would obscure toxicity or dangerously alter drug metabolism.

• - significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate study therapy.

• - prior radiotherapy to the brain.

• - prior cytotoxic or non-cytotoxic drug therapy or experimental drug therapy for the brain tumor.

• - prior Gliadel wafers.

• - concurrent participation in any other clinical trial.

• - concurrent GM-CSF (granulocyte-macrophage colony-stimulating factor) - concurrent stereotactic radiosurgery or brachytherapy.

• - concurrent major surgical procedure.

- other concurrent anticancer therapy, including chemotherapy, hormonal therapy, radiotherapy, or immunotherapy

OBJECTIVES: Primary.

• - To investigate the safety and tolerability of bevacizumab in combination with temozolomide and external beam fractionated regional radiotherapy as first-line treatment in patients with newly diagnosed glioblastoma multiforme or gliosarcoma.

(Pilot phase)

• - To estimate the overall survival of patients treated with this regimen.

(Expansion phase) Secondary.

• - To further investigate the safety and tolerability of this regimen in these patients.

(Expansion phase)

• - To isolate DNA, RNA, and protein from frozen and paraffin-embedded archival tumor samples for evaluations, such as immunohistochemical pathway profiling of vascular endothelial growth factor (VEGF)-dependent angiogenic pathways, gene expression microarray, and O-6 methylguanine DNA methyltransferase (MGMT) promoter methylation status to define important molecular features of treatment response.

OUTLINE: This is a multicenter study. Patients undergo external beam fractionated regional radiotherapy once daily 5 days a week for 6 weeks and receive concurrent oral temozolomide once daily for 6 weeks. Patients also receive bevacizumab IV over 30-90 minutes every 2 weeks beginning on the first day of radiotherapy and continuing in the absence of disease progression or unacceptable toxicity. Beginning 2-5 weeks after completion of radiotherapy, patients receive oral temozolomide on days 1-5. Treatment with temozolomide repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Blood and frozen and paraffin-embedded tumor tissue samples are collected for biomarker and genetic analysis. After completion of study treatment, patients are followed up periodically.

Arms

Experimental: bevacizumab, temozolomide, external beam radiation

Interventions

Biological: - bevacizumab

Drug: - temozolomide

Radiation: - external beam radiation therapy