Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Avastin and Temozolomide
Intervention description: This is Phase II study with the combination of Avastin & Temozolomide for unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up to 4 cycles of Avastin & Temozolomide . Avastin administered at 10 mg/kg every 14 days beginning minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide will be dosed at 200 mg/m2 daily x 5 days in 28-day cycle. Patients will have baseline MRI & repeat MRI every 4 weeks. If there is no evidence of disease progression after each cycle, or unacceptable toxicity, or as determined by investigators, patient non-compliance or patient withdraws consent to continue therapy & requests discontinuation, patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT therapy, & future therapy after 4 cycles will be at discretion of patient & treating physicians.
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioma; Temozolomide; Temodar; Avastin; Bevacizumab; GBM; Gliosarcoma; Multifocal GBM; Brain tumor; Unresectable GBM; Glioblastoma multiforme

Summary:

      Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in
      combination with standard 5-day temozolomide in terms of response rate.

      Secondary objective- To determine safety of Avastin & Temozolomide in unresectable
      glioblastoma patients
    

Eligibility criteria:

        Inclusion Criteria:

        Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma.
        Patients will be unresectable or have multifocal disease.

          -  Age ≥ 18years & life expectancy of >12 weeks

          -  Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.

          -  Interval of <1 week between prior biopsy/4 weeks from surgical resection & enrollment
             on protocol

          -  Karnofsky ≥60%

          -  Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter

          -  Serum creatinine ≤1.5 mg/dl, serum SGOT & bilirubin ≤1.5 x ULN

          -  For patients on corticosteroids, they must have been on stable dose for 1 week prior
             to entry, if clinically possible, & dose should not be escalated over entry dose level

          -  Signed informed consent approved by IRB prior to patient entry

          -  No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan

          -  If sexually active, patients will take contraceptive measures for duration of
             treatments

        Exclusion Criteria:

          -  Pregnancy/breast feeding

          -  Co-medication that may interfere with study results

          -  Active infection requiring IV antibiotics

          -  Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor

          -  Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan

        Avastin-Specific Concerns:

          -  Inadequately controlled hypertension

          -  Any prior history of hypertensive crisis/hypertensive encephalopathy

          -  New York Heart Association Grade II or > congestive heart failure

          -  History of myocardial infarction/unstable angina < 6 months prior to study enrollment

          -  History of stroke/transient ischemic attack < 6 months prior to study enrollment

          -  Significant vascular disease

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis/coagulopathy

          -  Major surgical procedure, open biopsy,/significant traumatic injury within 28 days
             prior to study enrollment/anticipation of need for major surgical procedure during
             course of study

          -  Core biopsy/other minor surgical procedure, excluding placement of vascular access
             device, <7 days prior to study enrollment

          -  History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months prior
             to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by either

          -  UPC ratio ≥1.0 at screening OR

          -  Urine dipstick for proteinuria ≥2+

          -  Known hypersensitivity to any component of Avastin

          -  Pregnant/lactating. Use of effective means of contraception in subjects of
             child-bearing potential

          -  Current, ongoing treatment with full-dose warfarin or its equivalent