Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide 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; erlotinib hydrochloride
Intervention description: 10mg/kg administered intravenously every 2 weeks; 150 mg/daily orally
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 115.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult glioblastoma; adult gliosarcoma

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. Erlotinib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. Giving bevacizumab
      together with erlotinib may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib
      works after radiation therapy and temozolomide in treating patients with newly diagnosed
      glioblastoma multiforme or gliosarcoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed newly diagnosed glioblastoma multiforme (GBM) or gliosarcoma

          -  Undergoing or plan to undergo treatment with radiotherapy and concurrent temozolomide
             for 6 weeks

          -  Unmethylated MGMT promoter status must be determined before completing radiotherapy

               -  Tumor must be MGMT negative to receive bevacizumab and erlotinib hydrochloride

          -  Patients who are post biopsy or tumor resection allowed provided a post-operative MRI
             is done no more than 96 hours after surgery (in order for an accurate assessment to be
             done post radiotherapy):

               -  Evaluable or measurable disease after resection of recurrent tumor is not
                  mandated for eligibility

          -  Patients who started radiotherapy and temozolomide prior to study entry are eligible
             as long as the gene methylation status is determined before starting bevacizumab and
             erlotinib hydrochloride

               -  Radiotherapy plans need to be verified to confirm the treatment plan meets the
                  study requirement based on the PI assessment

               -  No progressive disease based on MRI or CT scan per the investigators assessment

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 70-100%

          -  Life expectancy > 12 weeks

          -  WBC > 3,000/μL

          -  ANC > 1,500/mm³

          -  Platelet count > 100,000/mm³

          -  Hemoglobin > 10 g/dL

          -  SGOT/SGPT < 3 times upper limit of normal (ULN)

          -  Bilirubin < 3 times ULN

          -  Creatinine < 1.5 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 3 months after
             completion of study treatment

          -  No significant medical illness that, in the investigator's opinion, cannot be
             adequately controlled with appropriate therapy, would compromise the patient's ability
             to tolerate this therapy, or any disease that will obscure toxicity or dangerously
             alter drug metabolism

          -  No proteinuria at screening, as demonstrated by either of the following:

               -  Urine protein:creatinine (UPC) ratio < 1.0

               -  Urine dipstick for proteinuria < 2+ OR ≤ 1g protein by 24-hour urine collection

          -  No inadequately controlled hypertension (defined as systolic blood pressure > 150 mm
             Hg and/or diastolic blood pressure > 100 mm Hg) on antihypertensive medications

          -  No history of hypertensive crisis or hypertensive encephalopathy

          -  No New York Heart Association class II-IV congestive heart failure

          -  No history of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  No history of stroke or transient ischemic attack within 6 months of study enrollment

          -  No symptomatic peripheral vascular disease

          -  No significant vascular disease (i.e., aortic aneurysm or aortic dissection)

          -  No evidence of bleeding diathesis or coagulopathy

          -  No significant traumatic injury within 28 days prior to study enrollment

          -  No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
             abscess within 6 months prior to study enrollment

          -  No serious, nonhealing wound, ulcer, or bone fracture

          -  No known HIV positivity

               -  HIV testing is not required for study participation

          -  No history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of
             the cervix), unless in complete remission and off of all therapy for that disease for
             a minimum of 3 years

        PRIOR CONCURRENT THERAPY:

          -  No chemotherapy is allowed prior to starting radiotherapy and temozolomide, including
             polifeprosan 20 with carmustine implant (Gliadel wafers)

          -  No major surgical procedure or open biopsy within 28 days prior to study enrollment or
             the anticipation of need for major surgical procedure during the course of the study

          -  No core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  Concurrent nonenzyme-inducing anticonvulsants allowed

               -  More than 2 weeks (before starting erlotinib hydrochloride and bevacizumab) since
                  prior and no concurrent enzyme-inducing anticonvulsant

          -  No other concurrent experimental agents

          -  Not concurrently participating in other clinical trials