HUMC 1612: Optune NovoTTF-200A System

Inclusion Criteria:

• Patients must have a minimum head circumference of 44 cm
• Patients must have a histologically- or cytologically-confirmed supratentorial high-grade glioma or supratentorial ependemoma.
• Patients with metastatic disease involving the infratentorium or spinal cord are eligible providing that they have a supratentorial tumor that is able to be targeted with TTFields.
• Eligible pathologic diagnoses include:

High-grade Glioma (WHO Grade III or IV): Anaplastic Astrocytoma, Astroblastoma, Diffuse Midline Glioma, Glioblastoma, Gliosarcoma Ependymoma (WHO Grade II or III):Ependymoma, Anaplastic Ependymoma

• Patients with high-grade glioma must must have be newly-diagnosed or have a tumor that is progressive or recurrent following standard treatment. Patients with ependymoma must have a tumor that is progressive or recurrent following standard treatment.
• Patients must have received the maximal feasible resection of their tumor and radiation therapy (unless contraindicated due to patient age) as part of their initial treatment prior to study enrollment.
• Patients must be enrolled before treatment begins. Treatment must start within 14 days of study enrollment.
• All clinical and laboratory studies to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated in the eligibility section.
• Newly-diagnosed patients must begin therapy within six weeks of the completion of radiotherapy, or within six weeks of surgical resection if radiotherapy is contraindicated.
• Recurrent high-grade glioma patients must begin therapy within four weeks of documented tumor progression by MRI scan.
• Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purpose of assessing the performance score.
• Able to undergo adequate tumor imaging, via magnetic resonance imaging (MRI) scan to evaluate disease evolution.
• Adequate hematologic, renal, liver function as demonstrated by laboratory values: ANC ≥ 1,000/ul Hemoglobin ≥8.0 gm/dl Platelet count ≥ 100,000/ul

Adequate Liver Function Defined As:

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age. Adequate Renal Function Defined As Either
• Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2

• or a serum creatinine less than or equal to the institutional normal for age

  • Negative pregnancy test in women of childbearing potential within 7 days of initiating investigational therapy
  • Recent mothers must agree not to breast feed while receiving medications on study
  • Patient or legal guardian must give written, informed consent or assent (when applicable).
  • Able to swallow and ingest oral medication or have a NG or G-tube for drug administration
  • Urine protein should be screened by urine analysis. If protein ≥ 2+ on urinalysis, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment.

Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1000 mg. UPC ratio is calculated using one of the following formula:

• [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL
• [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
• Adequate Coagulation Defined As: PT/INR ≤ 1.5 x upper limit of normal

Exclusion Criteria:

• Age less than 5 or greater than or equal to 18 years
• Head circumference < 44 cm
• Absence of supratentorial tumor
• Use of any other investigational drug within five half-lives of that drug prior to the initiation of protocol therapy
• Anti-cancer therapy within 4 weeks prior to the initiation of protocol therapy (6 weeks for mitomycin and nitrosureas, 4 weeks for curative-intent radiotherapy, and 2 weeks for palliative radiotherapy)
• Any National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE version 4.0) >Grade 1 toxicities from prior chemotherapy or radiotherapy that could impact on safety outcome assessment
• Any surgery within 14 days prior to initiation of protocol therapy (excluding shunt or line insertion)
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias.
• Evidence of increased intracranial pressure (midline shift > 5mm, clinically significant papilledema, vomiting and nausea or reduced level of consciousness) Patients receiving escalating doses of corticosteroids to control symptoms of increased intracranial pressure (e.g., require a stable or decreasing dose of corticosteroids for at least 7 days prior to enrollment) will also be excluded.
• Known > Grade 1 intracranial or intratumoral hemorrhage either by CT or MRI scan within the last 1 month. Patients with resolving hemorrhage changes, punctuate hemorrhage or hemosiderin may enter the study
• Pregnant female patients, Pregnancy tests with a negative result must be obtained in all post-menarchal females.
• Lactating females must agree they will not breastfeed a child while on this study.
• Males and females of reproductive potential may not participate unless they agree to use an effective contraceptive method and continue to do so for at least 6 months after the completion of therapy.
• Any serious and/or unstable pre-existing medical, psychiatric or other condition which in the Investigator's opinion could interfere with subject safety, obtaining written informed consent, or compliance with the study protocol
• Known hypersensitivity to temozolomide or bevacizumab
• Patients who are unable to take oral medications because of significant uncontrolled vomiting will be excluded.
• Patients must not have a history of myocardial infarction, severe or unstable angina, clinically significant peripheral vascular disease, Grade 2 or greater heart failure, or serious and inadequately controlled cardiac arrhythmia.
• Patients must not have a known clinically significant bleeding diathesis or coagulopathy
• Patients who have experienced arterial thromboembolic events, including transient ischemic attacks or cerebrovascular accidents are excluded from participation.
• Patients must not have been previously diagnosed with a deep venous thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition (e.g., protein S, protein C, antithrombin III deficiency, Factor V Leiden or Factor II G202'0A mutation, homocysteinemia, or antiphospholipid antibody syndrome).
• Patients must not have a history of an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 6 months prior to study entry.
• Patients with a serious or non-healing wound, ulcer, or bone fracture are not eligible for this study.
• Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies are ineligible.