A Phase II Study of Optune (NovoTTF) in Combination With Bevacizumab (BEV) and Temozolomide (TMZ) in Patients With Newly Diagnosed Unresectable Glioblastoma (GBM)
Condition: Cancer of Brain and Nervous System
MeSH terms: Glioblastoma; Brain Neoplasms
Intervention: NovoTTF100A; Bevacizumab; Temozolomide
Intervention MeSH terms: Bevacizumab; Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 22 Years
Healthy volunteers: No

Summary:

      All patients will complete best standard of care radiation, temozolomide and bevacizumab (6
      weeks). Within two weeks of completion of this initial treatment period, study patients will
      be fitted with the NovoTTF-100A System and treated continuously. They will be treated with
      TTFields for 12 months for an average of 18 hours per day. The patient may elect to take a
      treatment break for a total of 3 days per month, for each month and still be in compliance.
      This will consist of wearing four electrically insulated electrode arrays on the head. The
      patients will also continue with maintenance temozolomide/ bevacizumab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 22 years of age

          -  Have undergone a brain biopsy via stereotactic or open technique

          -  Pathological evidence of GBM using WHO classification criteria

          -  Planned 6 weeks of concurrent chemoradiotherapy post-biopsy concomitant with
             temozolomide (45-70Gy)

          -  Karnofsky scale greater than or equal to 70

          -  Life expectancy at least 3 months

          -  Baseline hemoglobin of > 8.0 gm/dL (with or without transfusion)

          -  Adequate coagulation defined as PT and INR < 1.5 times the upper limit of normal

          -  Signed informed consent

          -  Able to start bevacizumab at least 2 weeks but no more than 4 weeks from date of
             biopsy

          -  Able to tolerate MRI of brain and have measurable disease.

          -  Participants of childbearing age must use effective contraception for at least 6
             months following completion of treatment.

        Exclusion Criteria

          -  Enrolled in another clinical treatment trial

          -  Pregnant or Breast-feeding

          -  Any other malignancy aside from localized basal cell or squamous cell carcinoma of the
             skin

          -  Significant co-morbidities at baseline which would prevent maintenance temozolomide

          -  Thrombocytopenia (platelet count < 100 x 103 )

          -  Neutropenia (absolute neutrophil count < 1.5 x 103 )

          -  CTC grade 4 non-hematological toxicity (except for alopecia, nausea, vomiting)

          -  Significant liver function impairment - AST or ALT > 3 times the upper limit of normal

          -  Total bilirubin> 2 times the upper limit of normal

          -  Significant renal impairment (serum creatinine> 1.7 mg/dL)

          -  Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other
             implanted electronic devices in the brain, or documented clinically significant
             arrhythmias.

          -  Infra-tentorial tumor

          -  Evidence of increased intracranial pressure (midline shift > 5mm, clinically
             significant papilledema, vomiting and nausea, or reduced level of consciousness)

          -  History of hypersensitivity reaction to temozolomide or a history of hypersensitivity
             to DTIC or hydrogel

          -  Inability to adequately cover treatment area with TTFields (Tumor Treating Fields)

          -  Inability to wear NovoTTF-100A System for an average of 18 hours per 24 hours

          -  Currently taking cytotoxic medications, non-steroidal ant-inflammatory drugs (NSAIDS),
             or enzyme inducing anticonvulsants.

          -  Currently taking anticoagulants or blood-thinners (Coumadin)

          -  Subjects meeting any of the following bevacizumab-specific contraindications are
             ineligible for study entry:

          -  Inadequately controlled hypertension (defined as systolic blood pressure greater than
             or equal to 150 and/or diastolic blood pressure > 100 mmHg)

          -  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, requiring surgical repair or
             recent peripheral arterial thrombosis) within 6 months prior to study enrollment

          -  History of hemoptysis (greater than or equal to a half teaspoon of bright red blood
             per episode) within 1 month prior to study enrollment

          -  Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic
             anticoagulation)

          -  Major surgical procedure or significant traumatic injury within 28 days prior to 1st
             bevacizumab infusion 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 within 6 months prior to
             study enrollment

          -  Serious, non-healing wound, active ulcer, or untreated bone fracture

          -  Proteinuria at screening as demonstrated by either urine protein: creatinine (UPC)
             ratio greater than or equal to 1.0 at screening OR urine dipstick for proteinuria
             greater than or equal to 2 or more (patients discovered to have greater than or equal
             to 2 or greater proteinuria on dipstick urinalysis at baseline should undergo a
             24-hour urine collection and must demonstrate less than or equal to 1g of protein in
             24 hours to be eligible).

          -  Known hypersensitivity to any component of bevacizumab