Tumor Treating Fields With Chemoradiation in Newly Diagnosed GBM

The study is an open-label pilot study in newly diagnosed glioblastoma patients following
surgery. Eligible patients will receive treatment with tumor treating fields therapy using
the Optune device starting less than 2 weeks prior to start of chemoradiation. Patients will
receive radiation and temozolomide at a routine treatment dose and schedule.

The expected toxicity is skin related, and patients will be followed closely with weekly skin
and neurological examinations during radiation therapy and for 8 weeks afterwards to capture
any delayed toxicity as they begin adjuvant therapy per routine treatment. As long as study
treatment is tolerated and their conditions remain stable, patients will continue the
treatment for up to 24 months.

Prior to enrollment, an exploratory analysis of radiation dosimetry will be performed by
phantom modeling incorporating the Optune arrays. The study incorporates three stages of
recruitment to confirm the safety of combining tumor treating fields therapy with concurrent
chemoradiation: a safety lead-in cohort of the first 6 patients enrolled, a second safety
lead-in cohort of 9 patients, and an expansion cohort with 15 additional patients.

Inclusion Criteria:

1. GBM or Gliosarcoma by histology

2. O6-methylguanine-DNA methyltransferase (MGMT) methylation status and isocitrate
dehydrogenase (IDH) mutation status must be assessed at the study site or patient's
referral center. MGMT status will be used for stratification purposes but will not
exclude patients from this study if they are either methylated, unmethylated, or
indeterminate, or in process at the time of enrollment. Similarly, subjects with
tumors that are IDH mutated or wild type are both eligible.

3. Supratentorial location

4. Maximum safe resection (including patients who can only safely be biopsied)

5. 22 years of age or older

6. Estimated survival of at least 12 weeks

7. Karnofsky Performance Status (KPS) 70% or greater at time of entry to study

8. Stable or decreasing steroid dose tapered down to 8mg or less of dexamethasone per day
(or bioequivalent of other corticosteroid) within 1 week after first use of TTField
therapy.

9. Willing and capable of providing written informed consent

10. Willingness to comply with all procedures, including visits or evaluations, imaging,
laboratory tests and rescue measures

11. Acceptable method of birth control (see appendix)

12. Have had a contrast-enhanced MRI within 72 hours after tumor resection procedure

13. The following time periods must have elapsed prior to study enrollment:

A) 3-4 weeks (21-28 days) from time of definitive surgery or 2-4 weeks (14-28 days) from
the time of biopsy for those who were only able to safely have a biopsy and not full
resection B) Radiation therapy should be started by 3-5 weeks (21-35 days) from surgery or
by 2-5 weeks (14-35 days) from time of biopsy and within 2 weeks (14 days) of starting
TTField therapy

Exclusion Criteria:

1. Craniotomy or stereotactic biopsy wound dehiscence or infection

2. Acquired immune deficiency (HIV+) (testing not required)

3. Presence of skull defects (bullets, metal fragments, missing bone)

4. Patients with implanted electronic medical devices (including but not limited to:
pacemaker, vagal nerve stimulator, or pain stimulator)

5. Prior invasive malignancy, unless disease free for 3 or more years

6. Recurrent malignant gliomas or higher grade gliomas transformed from previous low
grade (II) glioma

7. Patients with any current Primary brain stem or spinal cord tumor

8. Prior use of temozolomide

9. Prior treatment with Avastin

10. Individuals requiring >8mg of dexamethasone per day within 7 days prior to Day 1 (high
dose steroid taper following craniotomy with >8mg of dexamethasone is allowed during
the screening period, but subjects must taper down to 8mg or less of dexamethasone (or
bioequivalent) within 7 days prior to enrollment into the study).

11. Clinically significant lab abnormalities at baseline showing bone marrow, hepatic, and
renal dysfunction:

- Thrombocytopenia (platelet count < 100 x 103/μL)

- Neutropenia (absolute neutrophil count < 1.5 x 103/μL)

- Common toxicity criteria (CTC) grade 4 non-hematological Toxicity (except for
alopecia, nausea, vomiting)

- Significant liver function impairment - Aspartate transaminase (AST) or Alanine
transaminase (ALT) > 3 times the upper limit of normal

- Total bilirubin > upper limit of normal

- Significant renal impairment (serum creatinine > 1.7 mg/dL)

12. Inability to swallow pills

13. Clinically significant or unstable comorbid medical condition (for example, active or
uncontrolled infection requiring systemic therapy, including known HIV or hepatitis B
or C virus; other active cancer within the prior 3 years with the exception of basal
cell carcinoma, cervical carcinoma in situ, or melanoma in situ)

14. Known current alcohol or drug abuse, per investigator discretion. Prior history of
substance abuse is permissible if subject has been sober for the past 3 years.

15. Any clinically significant psychiatric condition that would prohibit understanding or
rendering of informed consent, or prohibit successful performance of study procedures

16. Patients with an allergy to or an inability to have gadolinium contrast dye
administered with MRI are not eligible.

17. Patients with aneurysm clips or implanted metal objects in the brain are not eligible.

18. Patients with significant skin breakdown be excluded from enrolling