Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme
Condition: Glioblastoma Multiforme; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Avastin; Temozolomide; Irinotecan
Intervention description: Avastin, by intravenous infusion, 10 mg/kg every 14 days; Oral temozolomide at 200 mg/m2 daily for 5 days; Irinotecan, by intravenous infusion, every other week (dose dependent upon if taking enzyme-inducing anti-epileptic drugs or if a blood test indicates the patient has the UGT 1A1 polymorphism)
Intervention MeSH terms: Bevacizumab; Irinotecan; 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: malignant glioma; glioblastoma multiforme; gliosarcoma; Avastin; bevacizumab; Temodar; temozolomide; Irinotecan; CPT-11; Pro00019065; Vredenburgh; Duke

Summary:

      The primary objective of the study is to determine the efficacy of Avastin in combination
      with temozolomide and irinotecan in terms of response rate. The secondary objectives are to
      describe the overall and progression-free survivals of unresectable patients treated with
      upfront Avastin, temozolomide and irinotecan and to assess the safety of Avastin,
      temozolomide and irinotecan in unresectable glioblastoma patients.

      This is a phase II study with the combination of Avastin, temozolomide and irinotecan for
      unresectable or multifocal World Health Organization (WHO) grade IV malignant glioma
      patients. Patients will receive up to four cycles of Avastin, temozolomide and irinotecan.
      Approximately 41 subjects will take part in this study at Duke.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of WHO grade IV primary
             malignant glioma (glioblastoma multiforme or gliosarcoma). Patients will be
             unresectable or have multifocal disease.

          -  Age > or = to 18 years and a life expectancy of >12 weeks.

          -  Evidence of measurable primary Central Nervous System (CNS) neoplasm on contrast
             enhanced MRI.

          -  An interval of at least one week between prior biopsy or four weeks from surgical
             resection and enrollment on this protocol.

          -  Karnofsky > or = to 60%.

          -  Hemoglobin > or = to 9g/dl, absolute neutrophil count (ANC) > or = to 1,500
             cells/microliter, platelets > or = to 125,000 cells/microliter.

          -  Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic oxaloacetic transaminase (SGOT) and
             direct bilirubin ≤ 1.5 times upper limit of normal (if the total bilirubin is greater
             than or equal to 1.5 x the upper limit of normal, then the direct bilirubin must be ≤
             1.5 x the upper limit of normal).

          -  Signed informed consent approved by the Institutional Review Board prior to patient
             entry.

          -  If sexually active, patients will take contraceptive measures for the duration of the
             treatments.

        Exclusion Criteria:

          -  Pregnancy or breast feeding

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids.

          -  Active infection requiring IV antibiotics.

          -  Treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the
             grade of the tumor.

          -  Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan.

        Avastin-specific Exclusion Criteria:

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
             diastolic blood pressure > 100 mmHg on antihypertensive medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC)
             ratio > or = to 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).

          -  Known hypersensitivity to any component of Avastin

          -  Pregnant (positive pregnancy test) or lactating. Use of effective means of
             contraception (men and women) in subjects of child-bearing potential