Bevacizumab and Sorafenib in Treating Patients With Recurrent Glioblastoma Multiforme
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: bevacizumab; sorafenib tosylate
Intervention MeSH terms: Bevacizumab; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; recurrent adult brain tumor

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. Sorafenib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and sorafenib
      may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving
      bevacizumab together with sorafenib may kill more tumor cells.

      PURPOSE: This phase II trial is studying the side effects and how well giving bevacizumab
      together with sorafenib works in treating patients with recurrent glioblastoma multiforme.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed glioblastoma multiforme as determined by pre-registration
             central pathology review

               -  Gliosarcoma allowed

          -  Must have evidence of tumor progression by MRI or CT scan following radiotherapy or
             the most recent anti-tumor therapy

          -  No more than 1 chemotherapy regimen for progressive or recurrent disease

          -  Bidimensionally measurable or evaluable disease by MRI or CT scan

          -  No evidence of CNS hemorrhage on baseline CT or MRI

               -  Patients with T1 hyperintensity confined to the surgical cavity which is felt
                  likely due to post surgical blood contaminating the intracavity cerebrospinal
                  fluid or irrigation that have not yet absorbed and which is not felt to
                  clinically or radiographically represent new spontaneous hemorrhage are eligible

               -  Patients with old blood products or hemosiderin without a history of spontaneous
                  bleeding are eligible

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Hemoglobin > 9.0 g/dL

          -  Total bilirubin ≤ 1.5 times upper limit of normal

          -  AST ≤ 3 times upper limit of normal

          -  Creatinine ≤ upper limit of normal

          -  Urine protein:creatinine ratio < 1 OR urine protein < 1,000 mg by 24-hour urine
             collection

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for six months after
             completion of study treatment

          -  Able to complete questionnaire(s) alone or with assistance

          -  Willing to return to NCCTG enrolling institution for follow-up

          -  Willing to provide mandatory blood samples for research purposes

          -  Not immunocompromised (other than that related to the use of corticosteroids)

          -  No known HIV positivity

          -  No concurrent uncontrolled illness including, but not limited to, the following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness/social situations that would limit compliance with study
                  requirements

          -  No inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 150 mm
             Hg or diastolic BP > 100 mm Hg while on antihypertensive medications)

               -  Patients with well-controlled hypertension are eligible

          -  No myocardial infarction or unstable angina within the past 6 months

          -  No congestive heart failure requiring the use of ongoing maintenance therapy for
             life-threatening ventricular arrhythmias

          -  No New York Heart Association class II-IV congestive heart failure

          -  No significant vascular disease (e.g., aortic aneurysm or aortic dissection)

          -  No peripheral arterial thrombosis within the past 6 months

          -  No stroke or transient ischemic attack within the past 6 months

          -  No history of hypertensive crisis or hypertensive encephalopathy

          -  No evidence of bleeding diathesis (greater than normal risk of bleeding) or
             coagulopathy (in the absence of therapeutic anticoagulation)

          -  No active or recent history of hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per
             episode) within the past 30 days

          -  No serious, nonhealing wounds, ulcers, or bone fractures

          -  No condition that impairs the ability to swallow pills (e.g., gastrointestinal tract
             disease resulting in an inability to take oral medication or a requirement for IV
             alimentation)

          -  No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
             the past 6 months

          -  No significant traumatic injury within the past 28 days

          -  No known hypersensitivity to any of the components of sorafenib or bevacizumab

          -  No other active malignancy within the past 3 years, except nonmelanoma skin cancer or
             carcinoma in situ of the cervix

               -  Patients with a history of prior malignancy must not be receiving specific
                  treatment (other than hormonal therapy) for that malignancy

          -  No co-morbid systemic illness or other concurrent severe disease that, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             significantly interfere with the proper assessment of safety and toxicity of the
             prescribed study regimen

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  At least 12 weeks since prior radiotherapy

          -  More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)

          -  More than 2 weeks since prior small molecule cell cycle inhibitors

          -  At least 1 week since prior fixed-dose corticosteroids (or no corticosteroids)

          -  No prior intratumoral chemotherapy, stereotactic radiosurgery or interstitial
             brachytherapy unless there is a separate lesion on MRI that is not part of the prior
             treatment field OR there is proof of recurrent disease based on biopsy, MRI
             spectroscopy, or PET scan

          -  No prior antiangiogenic therapy

          -  No prior surgical procedures affecting absorption

          -  More than 7 days since prior core biopsy or other minor surgical procedures

               -  Placement of a vascular access device is allowed

          -  More than 28 days since prior major surgical procedure or open biopsy

          -  No concurrent major surgical procedure

          -  No other concurrent investigational agents

          -  No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, fosphenytoin,
             carbamazepine, phenobarbital, or primidone)

          -  No other concurrent potent CYP3A4 inducers (e.g., rifampin or St. John's wort)

          -  No concurrent therapeutic anticoagulation with warfarin

               -  Prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial
                  access devices allowed provided the INR < 1.5

               -  Therapeutic anticoagulation with low molecular weight heparin allowed