Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Gliosarcoma; Central Nervous System Neoplasms
Intervention: bevacizumab; temozolomide; external beam radiation therapy
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult giant cell glioblastoma; adult gliosarcoma; adult glioblastoma

Summary:

      RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the
      growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such
      as temozolomide, work in different ways to stop the growth of tumor cells, either by killing
      the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to
      kill tumor cells. Giving bevacizumab together with temozolomide and radiation therapy may
      kill more tumor cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab
      together with temozolomide and external beam radiation therapy works when given as first-line
      therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.
    

Eligibility criteria:

        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