TTFields and Pulsed Bevacizumab for Recurrent Glioblastoma
Condition: Glioblastoma Multiforme; Glioblastoma; Malignant Glioma; GBM
MeSH terms: Glioblastoma; Glioma
Intervention: Bevacizumab; Optune; Brain MRI; Quality of Life Questionnaires
Intervention description: Bevacizumab will be given at 10mg/kg IV every 2 weeks.; Optune will be worn continuously for 12 months. Optune is programmed by Novocure to deliver 200 kHz TTFields in two sequential, perpendicular field directions at a maximal intensity of 707mARMS. There will be no adjustments made to the device by investigators or patients/caregivers.; Brain MRI will be done at screening and every 8 weeks.; The quality of life questionnaires will be performed within 14 days of treatment and every 4 weeks.
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 22 Years
Healthy volunteers: No

Summary:

      Glioblastoma multiforme (GBM) is the most common and deadliest primary malignant neoplasm of
      the central nervous system in adults. Despite an aggressive multimodality treatment approach
      including surgery, radiation therapy and chemotherapy, overall survival remains poor.
      Novocure has shown that when properly tuned, very low intensity, intermediate frequency
      electric fields (TTFields) stunt the growth of tumor cells. The Optune system (NovoTTFTM
      Therapy) is a portable battery operated device, which produces TTFields within the human body
      by means of surface transducer arrays. The TTFields are applied to the patient by means of
      surface transducer arrays that are electrically insulated, so that resistively coupled
      electric currents are not delivered to the patient. Optune is currently FDA-approved as a
      single modality treatment for recurrent GBM when both surgical and radiotherapy options have
      been exhausted as well as combination with adjuvant temozolomide for newly diagnosed GBM.

      This research study is being performed to determine whether or not TTFields combined with
      pulsed bevacizumab treatment increases overall survival in patients with
      bevacizumab-refractory GBM compared to historical controls treated with continuous
      bevacizumab alone or in combination with other chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed GBM, WHO grade IV. GBM variants and secondary GBM are allowed
             in any recurrence (including multiple) and have been treated with radiation and
             chemotherapy.

          -  Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO
             criteria.

          -  Patient is a candidate for, and agrees to proceed with additional bevacizumab
             treatment.

          -  Male or female at least 22 years of age or older.

          -  Karnofsky Performance Scale (KPS) ≥ 60%.

          -  Planned treatment with TTFields therapy.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 14 days of treatment.

          -  Participants of childbearing/reproductive potential must use effective contraception.

          -  Participants must be able to understand and willing to comply with protocol
             requirements as assessed by the investigator.

          -  Signed informed consent according to institutional guidelines prior to registration.

        Exclusion Criteria:

          -  Inability to undergo brain MRI due to medical or personal reasons.

          -  Currently receiving investigational agents that are intended as treatments of
             recurrent GBM.

          -  Skull defect such as missing bone or bullet fragments.

          -  Uncontrolled intercurrent illness including, but not limited to symptomatic congestive
             heart failure, unstable angina pectoris, heart attack within the previous 12 months,
             stroke (except for TIA) within the previous 6 months, or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  Intracranial hemorrhage except for tumor associated micro hemorrhage.

          -  Women who are pregnant or breastfeeding.

          -  Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, vagus
             nerve stimulator, and other implanted electronic devices in the brain or the spinal
             cord.

          -  Tumor located entirely in the infratentorium.

          -  History of hypersensitivity to hydrogel.