Tumor Treating Fields for the Treatment of Brainstem Gliomas

Inclusion Criteria:

• Age >= 18 years

• Karnofsky performance status >= 70%

• Life expectancy > 12 weeks as determined by the investigator

• Diagnosis of glioma with at least partial involvement or invasion of thalamus,cerebral peduncles, midbrain, pons, or medulla. Confirmation of diagnosis by biopsyor maximal safe resection preferred. If multi-disciplinary tumor board recommend nobenefit and likely harm of attempting biopsy then can establish consensus clinicaldiagnosis. If foregoing biopsy then tumor board will estimate tumor stage based onclinical presentation and radiographic findings.

• Completion of all previous therapy (including surgery and radiotherapy) for thetreatment of cancer >= 4 weeks before the start of study therapy.

• Willingness and ability of the subject to comply with scheduled visits, drugadministration plan, protocolspecified laboratory tests, other study procedures, andstudy restrictions.

• Evidence of a personally signed informed consent indicating that the subject isaware of the neoplastic nature of the disease and has been informed of theprocedures to be followed, the experimental nature of the therapy, alternatives,potential risks and discomforts, potential benefits, and other pertinent aspects ofstudy participation.

• Patients must have adequate organ and marrow function, within 28 days of Cycle 1 Day 1 of Temozolomide, as defined below:

Hematology:

• Hemoglobin >= 9.0 g/dl (no transfusions allowed within 7 days of cycle 1 day 1 tomeet entry criteria) (within 28 days of cycle 1 day 1 of temozolomide)

• White blood cell (WBC) >= 2000/uL (after at least 7 days without growth factorsupport or transfusion) (within 28 days of cycle 1 day 1 of temozolomide)

• Absolute neutrophil count (ANC) >= 1,500/mcL (after at least 7 days without growthfactor support or transfusion) (within 28 days of cycle 1 day 1 of temozolomide)

• Platelets >= 100,000/mcL (no transfusions allowed within 7 days of cycle 1 day 1 tomeet entry criteria) (within 28 days of cycle 1 day 1 of temozolomide)

• Prothrombin time (PT)/partial thromboplastin time (PTT) =< 1.5 x upper limit ofnormal (ULN) (within 28 days of cycle 1 day 1 of temozolomide)

Chemistry

• Total bilirubin =< 2 institutional upper limit of normal (ULN) (within 28 days ofcycle 1 day 1 of temozolomide)

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 institutionalupper limit of normal (ULN) (within 28 days of cycle 1 day 1 of temozolomide)

• Serum creatinine =< 2 mg/dL (or glomerular filtration rate >= 40 mL/min) (within 28days of cycle 1 day 1 of temozolomide)

• The effects of combination therapy with tumor treating fields (TTF) and temozolomideon the developing human fetus are unknown. For this reason and because othertherapies used in this trial are known to be teratogenic, female of child-bearingpotential (FCBP) must have a negative serum or urine pregnancy test prior tostarting therapy.

• FCBP and men must agree to use adequate contraception (hormonal or barrier method ofbirth control; abstinence) prior to study entry and for the duration of studyparticipation. Should a woman become pregnant or suspect she is pregnant while sheor her partner is participating in this study, she should inform her treatingphysician immediately. Men treated or enrolled on this protocol must also agree touse adequate contraception prior to the study, for the duration of studyparticipation, and 12 months after completion of TTF and Temozolomideadministration. A female of childbearing potential (FCBP) is a sexually mature womanwho: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has notbeen naturally postmenopausal for at least 24 consecutive months (i.e., has hadmenses at any time in the preceding 24 consecutive months.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Patients who have completed chemotherapy or radiotherapy more than 26 weeks prior toentering the study.

i. Completion of radiotherapy 8-12 weeks prior to starting the tumor treating fields will be considered a minor deviation.

ii. Completion of radiotherapy 13-26 weeks prior to starting the tumor treating fields will be considered a major deviation.

• Patients who are receiving any other investigational agents or an investigationaldevice within 21 days before first administration of study device.

• History of allergic reactions attributed to compounds of similar composition tothose used for transducer placement.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

• Significant cardiovascular disease (eg, myocardial infarction, arterialthromboembolism, cerebrovascular thromboembolism) within 3 months prior to start ofstudy therapy; angina requiring therapy; symptomatic peripheral vascular disease;New York Heart Association Class 3 or 4 congestive heart failure; or uncontrolledGrade ≥3 hypertension (diastolic blood pressure ≥100 mmHg or systolic blood pressure ≥160 mmHg) despite antihypertensive therapy.

• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviraltherapy are ineligible because of increased risk of lethal infections when treatedwith marrow-suppressive therapy such as Temozolomide. Appropriate studies will beundertaken in patients receiving combination antiretroviral therapy when indicated.