Expedited Laser Interstitial Thermal Therapy + Chemoradiation For Newly Diagnosed High Grade Gliomas

Primary Objective To determine the safety and feasibility of reducing the time interval
between LITT and the start of chemoradiation to ≤ 7 days.

The primary endpoint (binary) for safety/feasibility will be defined as the occurrence of one
or more of the following within each patient during a window of observation from the
completion LITT to the end of radiation:

- Wound dehiscence, grade 3 {CTCAE v4.0)

- Seizures, grade 3 (CTCAE v4.0) in patients without a prior history of seizures and on
adequate anti-seizure medications

- Cerebral edema, grade 4 (CTCAE v4.0)

- Failure to complete of 60 Grays (Gy) of radiation

Secondary Objective(s) To estimate the proportion of patients requiring adjustments in
radiation plans post-LITT.

Secondary Endpoint: Requirement of an adjustment in the radiation plan to account for
post-LITT tissue distortion.

Study design This study will be a 2-stage, single-institution safety and feasibility trial.
Patients will be evaluated by a neuro-oncology team consisting of a neurosurgeon trained in
LITT, radiation oncologist and medical oncologist prior to surgery. Evaluable patients will
have a histologic diagnosis of high-grade glioma, complete LITT, and are candidates for
standard concurrent radiation (60 Gy) and temozolomide as determined by the treating
physician. Concurrent chemoradiation will begin within 7 days of the LITT procedure.

Inclusion Criteria:

- Subjects must have suspected high grade glioma by MRI

- Subjects must have received no prior therapies for this disease.

- Patients must be considered appropriate candidates for LITT.

- Karnofsky Performance status ≥ 60%

- Subjects must have normal organ and marrow function as defined below. Measures of
function must be within 14 days prior to registration.

- Absolute neutrophil count (ANC) ≥ 1500 cells/mm3, platelets ≥ 100,000 cells/mm3,
hemoglobin ≥ 10.0 g/dl. Use of transfusion or other intervention to achieve this
hemoglobin level is acceptable.

- Blood urea nitrogen ≤ 30mg/dl and creatinine ≤ 1.7 mg/dl

- Bilirubin ≤ 2.0 mg/dl, Aspartate aminotransferase/ Alanine aminotransferase
(AST/ALT) ≤ 3x upper limit of normal

- Electrocardiogram without evidence of acute cardiac ischemia

- Prothrombin time/international normalized ratio (PT INR) <1.4

- Women of childbearing potential and male participants must practice adequate
contraception.

- For women of childbearing age, negative pregnancy test within 14 days prior to
registration

- Subjects must have the ability to understand and the willingness to sign a written
informed consent document.

Exclusion Criteria:

- Patients not eligible to obtain MRI with and without contrast

- Recurrent or multifocal high-grade glioma

- Cerebral edema, grade 3 or greater prior to surgery

- Post-operative complications including significant neurological decline or hemorrhage
that causes a drop in Karnofsky performance status to less than 60 or renders the
patient not suitable for chemoradiation as determined by their treating physician

- Prior history of invasive malignancy, except non-melanoma skin cancer, unless disease
free for ≥ 3 yrs

- Prior radiation resulting in overlapping radiation fields

- Severe co-morbidity that would confer excess risk of surgery, radiation or
chemotherapy, defined as follows:

- Unstable angina and/or congestive heart failure within the last 6 months

- Transmural myocardial infarction within the last 6 months

- Evidence of recent myocardial infarction or ischemia by the findings of S-T
elevations of ≥ 2 mm using the analysis of an EKG performed within 14 days of
registration

- New York Heart Association grade II or greater congestive heart failure requiring
hospitalization within 12 months prior to registration

- History of stroke, cerebral vascular accident (CVA) or transient ischemic attack
within 6 months

- Serious and inadequately controlled cardiac arrhythmia

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of
registration

- Acquired immune deficiency syndrome (AIDS) based upon current Center for Disease
Control and Prevention (CDC) definition; note, however, that HIV testing is not
required for entry into this protocol. The need to exclude patients with AIDS from
this protocol is necessary because the treatments involved in this protocol may be
significantly immunosuppressive.

- Active connective tissue disorders, such as lupus or scleroderma, that in the opinion
of the treating physician may put the patient at high risk for radiation toxicity.

- Any other major medical illnesses or psychiatric impairments that in the
investigator's opinion will prevent administration or completion of protocol therapy.

- Pregnancy or women of childbearing potential and men who are sexually active and not
willing/able to use medically acceptable forms of contraception.

- Pregnant or lactating women

- Subjects receiving other investigational agents.