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.
