Study of Bevacizumab Plus Temodar and Tarceva in Patients With Glioblastoma or Gliosarcoma
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Bevacizumab; Tarceva; Temozolomide
Intervention description: Patients are given 10 mg/kg IV Q2 weeks.; Patients receive 150 mg PO daily. If patients are not experiencing intolerable toxicity, they may escalate their dose to 200 mg PO daily. If patients are experiencing intolerable toxicity, their dose will be held until the toxicity improves or resolves, then re-treated at a lower dose level, i.e. 100 mg PO daily.; Patients receive 200 mg/m2 for Days 1-5 of every 28 day cycle. Although the calendar days may be slightly altered, the patient should always receive this dose for 5 days within a treatment cycle. If the patient experiences certain toxicities specified in the protocol, Temodar will be held then given at a reduced dose, i.e. 150 mg/m2 Days 1-5.
Intervention MeSH terms: Bevacizumab; Temozolomide; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 74.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; Bevacizumab; Avastin; Erlotinib; Tarceva; Temozolomide; Temodar

Summary:

      This is a phase II study of Bevacizumab plus Temodar and Tarceva in patients with
      non-progressive glioblastoma or gliosarcoma. Patients must have stable disease immediately
      following a standard course of up-front radiotherapy and Temodar. All patients will receive
      Bevacizumab, Temodar and Tarceva. A total of 60 patients will be enrolled. Our hypothesis is
      that the combination of Bevacizumab plus Temodar and Tarceva will increase survival over that
      seen in historical controls who have newly diagnosed, non-progressive glioblastoma or
      gliosarcoma following radiotherapy plus Temodar and use Temodar alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically proven, non-progressive glioblastoma multiforme (GBM) or
             gliosarcoma (GS) with stable disease immediately following XRT + TMZ. All patients
             will receive Bevacizumab plus Tarceva and TMZ.

          -  Biopsy or resection must have been performed prior to RT + TMZ.

          -  No chemotherapy is allowed prior to starting RT + TMZ, including Gliadel Wafers.

          -  Patients will have started RT + TMZ prior to registration and study entry and are
             eligible as long as they do not have progressive disease and can start Bevacizumab +
             TMZ and Tarceva within 4 weeks after the completion of RT + TMZ. Patients MUST have
             been treated with at least 54 Gy radiotherapy (60 Gy recommended) and MUST have
             received Temodar concurrently with radiotherapy for eligibility for this study.

          -  Patients may or may not have measurable or evaluable disease on contrast MR imaging. A
             post-radiotherapy MRI scan must document stable disease.

          -  Patients must be > 18 years old and with a life expectancy > 12 weeks.

          -  Patients must have a Karnofsky performance status of ≥ 70.

          -  Patients must have adequate bone marrow function (WBC > 3,000/µl, ANC > 1,500/mm3,
             platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function
             (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5
             mg/dL) before starting therapy. These tests must be performed within 14 days prior to
             initial treatment.

        Exclusion Criteria:

          -  Patients must not have evidence of recent hemorrhage on baseline MRI of the brain,
             with the following exceptions: presence of hemosiderin, resolving hemorrhage changes
             related to surgery, presence of punctuate hemorrhage in the tumor.

          -  Patients must not have any significant medical illnesses 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.

          -  Patients must not have proteinuria at screening as demonstrated by either

               -  Urine protein: creatinine (UPC) ratio ³ 1.0 at screening OR

               -  Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria
                  on dipstick urinalysis at baseline should undergo a 24 hour urine collection and
                  must demonstrate ≤ 1g of protein in 24 hours to be eligible).

          -  Patients must not have inadequately controlled hypertension (defined as systolic blood
             pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive
             medications.

          -  Patients must not have any prior history of hypertensive crisis or hypertensive
             encephalopathy.

          -  Patients must not have New York Heart Association Grade II or greater congestive heart
             failure (see Appendix E).

          -  Patients must not have history of myocardial infarction or unstable angina within 12
             months prior to study enrollment.