Study of Laser Interstitial Thermal Therapy (LITT) in Recurrent Glioblastoma

Study Drug/Procedure Administration:

If you are found to be eligible to take part in this study, you will be scheduled to have the
LITT procedure. An MRI will be performed the day before the procedure to produce images of
your brain to direct the study doctor to the areas that should be treated. The LITT procedure
will then be performed the next day. You will sign a separate consent form for the LITT
procedure that explains this procedure and its risks in more detail.

You will then receive standard of care hospitalization after surgery. You will have an MRI
within 48 hours after the procedure to check the status of the disease.

You will have 14 - 35 days for recovery from the LITT procedure. You will not take lomustine
during this period. After the recovery period, you will take lomustine by mouth on Day 1 of
every 42-day cycle.

You should take lomustine by mouth on an empty stomach before bed (2 hours after or 1 hour
before food).

Length of Treatment:

You will take lomustine for up to 6 cycles. You will no longer be able to take the study drug
if the disease gets worse, if you have intolerable side effects, or if you are unable to
follow study directions.

Your participation in the study will be over after follow-up.

Study Visits:

On the day of the LITT procedure:

- You will have a physical exam, including a neurological exam.

- You will have MRI scans to help the surgeon perform LITT.

- Blood (about 2 teaspoons) will be drawn for biomarker testing.

- Tumor tissue will be collected to confirm the diagnosis and for biomarker testing during
the LITT procedure.

Within 2 days after the LITT procedure, you will have an MRI.

About 14 days after the LITT procedure:

- You will have a physical exam, including a neurological exam.

- Blood (about 2 teaspoons) will be drawn for routine tests. If you can become pregnant,
this will also include a pregnancy test.

- You will complete the questionnaire about your quality of life.

- You will have an MRI.

When you begin receiving lomustine, you will have study visits in 42-day cycles.

On Day 1 of each cycle:

- You will have a physical exam, including a neurological exam.

- Blood (about 2 teaspoons) will be drawn for routine test. If you can become pregnant,
this will also include a pregnancy test.

- You will complete the questionnaire about your quality of life.

- You will have an MRI.

On Days 15 and 29 of each cycle, blood ( about 2 teaspoons) will be drawn for routine tests.

Every 6 or 8 weeks, blood (about 2 teaspoons) will be drawn for biomarker testing.

At any time during the study, extra tests may be performed if the doctor thinks they are
needed. The study doctor will tell you more about any extra tests.

End-of-Study Visit:

About 6 weeks after stopping the study drug:

- You will have a physical and neurological exam.

- You will complete the questionnaire about your quality of life.

- You will have an MRI scan.

Follow-Up:

Every 3 months after your last dose of the study drug, the study staff will call and ask how
you are feeling. This call should take about 5-10 minutes.

If you stop the study drug for any reason other than the disease getting worse, you will
visit the clinic every 3 months unless the disease gets worse. At these visits:

- You will have a physical exam, including a neurological exam.

- You will complete the questionnaire about your quality of life.

- You will have an MRI.

Inclusion Criteria:

1. Patients must have histologically-proven, recurrent supratentorial grade IV
glioblastoma (or grade III IDH-wildtype anaplastic astrocytoma), for which a complete
surgical resection is unsafe due to location, shape, or size of the tumor. Diagnosis
of recurrence will be established by biopsy and frozen section immediately prior to
initiating LITT procedure. If findings on frozen section are not consistent with
recurrence (glioblastoma or recurrent IDH-wildtype anaplastic astrocytoma), decision
to proceed with LITT procedure will be at the discretion of the neurosurgeon (only
patients with histologically-proven recurrent tumor will be evaluable for efficacy).

2. All patients must sign an informed consent indicating that they are aware of the
investigational nature of this study. Patients must have signed an authorization for
the release of their protected health information. Patients must be registered prior
to treatment on study.

3. Patients must be >/= 18 years old.

4. Patients must have a Karnofsky Performance Score (KPS) >60.

5. Patients must have received standard of care therapy with chemoradiation with
temozolomide followed by adjuvant chemotherapy with temozolomide. Patients may have
received one additional chemotherapy regimen (other than lomustine) in addition to
adjuvant temozolomide prior to study entry (patients at either first or second
recurrence are eligible).

6. In the context of this clinical trial, a lesion suitable for LITT is single,
enhancing, supratentorial, at least 2 cm from inner table of skull over the
hemispheric convexity, and >1 cm, but < 4 cm in cross-sectional dimension, including
thalamic tumor (
7. Patients must have stable cardiovascular, neurovascular and neurological status, and
be considered surgical candidates, as determined by any relevant pre-operative
assessments, at the neurosurgeon's discretion.

8. Patients must not be receiving concurrent anti-tumor treatment and must have recovered
from toxicity of prior treatment. Minimum interval required: 1) >6 weeks following
nitrosourea chemotherapy; 2) >4 weeks after recovering from any non-nitrosourea drug
or systemic investigational agent; 3) >2 weeks after receiving any non-cytotoxic
anti-tumor drug; 4) > 4 weeks after receiving radiation therapy (>12 weeks following
upfront concurrent chemoradiation); ); 5) >2 weeks following Optune device use.

9. Patients must not have previously undergone an intracranial LITT procedure. Patients
must have adequate bone marrow function (white blood cell (WBC) > 3,000/µl, ANC >
1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 gm/dl), adequate liver
function (SGOT and bilirubin < 2 times ULN), and adequate renal function (creatinine <
1.5 mg/dL) before starting therapy. These tests must be performed within 14 days (+ 3
working days) prior to registration. Eligibility level for hemoglobin and platelets
may be reached by transfusion.

10. Women of childbearing potential must have a negative B-HCG documented within 7 days
prior to registration and must agree to practice adequate contraception as defined
below. Non-childbearing potential (i.e., physiologically incapable of becoming
pregnant), includes any female who has had: 1. A hysterectomy 2. A bilateral
oophorectomy 3. A bilateral tubal ligation 4. Is post-menopausal: Subjects not using
hormone replacement therapy (HRT) must have experienced total cessation of menses for
>/= 1 year and be greater than 45 years in age, OR, in questionable cases, have a
follicle stimulating hormone (FSH) value >40 mIU/mL and an estradiol value < 40pg/mL
(<140 pmol/L).

11. (10. continued) Subjects using HRT must have experienced total cessation of menses for
>= 1 year and be greater than 45 years of age OR have had documented evidence of
menopause based on FSH and estradiol concentrations prior to initiation of HRT.

12. (11. continued) Childbearing potential includes any female who has had a negative
serum pregnancy test within 7 days of study registration, and agrees to use adequate
contraception. Acceptable contraceptive methods, when used consistently and in
accordance with both the product label and the instructions of the physician, are as
follows: 1. Complete abstinence from sexual intercourse for 14 days before starting
treatment, through the treatment, and for at least 1 month after the last dose of
temozolomide. 2. Oral contraceptive, either combined or progestogen alone. A second
barrier method is required during the first month of treatment with oral
contraceptives.

13. (12. continued) 3. Injectable progesterone 4. Implants of levonorgestrel. 5.
Estrogenic vaginal ring. 6. Percutaneous contraceptive patches. 7. Intrauterine device
(IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per
year. 8. Male partner sterilization (vasectomy with documentation of azoospermia)
prior to the female subject's entry into the study, and this male is the sole partner
for that subject. 9. Double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository). Female participants who are lactating should
discontinue nursing prior to the first dose of temozolomide and should refrain from
nursing throughout the treatment period and for 42 days following the last dose of
lomustine.

Exclusion Criteria:

1. Patients must not have received prior treatment with bevacizumab.

2. Patients must not have had prior treatment of glioblastoma with stereotactic
radiosurgery, brachytherapy, or carmustine-impregnated wafers (Gliadel).

3. Patients must not have symptoms attributed to mass effect of the tumor (despite
corticosteroid treatment) that would be better treated with debulking surgery, or
wherein surgical debulking in the first 30 days following LITT procedure would be
anticipated for symptom management.

4. Patients unable to undergo MRI are not eligible.

5. Patients with progression of multifocal tumors or tumors involving the posterior fossa
(brainstem and cerebellum) will be excluded, as will patients where the anticipated
treatment margin will be within 5 mm of critical intracranial structures (e.g.,
primary branches of cerebral vessels, dural sinuses, hypophysis or cranial nerves).

6. Patients may not have undergone previous treatment with lomustine.

7. Patients must not have any significant medical illnesses that in the investigator's
opinion cannot be adequately controlled with appropriate therapy or would compromise
the patient's ability to tolerate this therapy.

8. Patients with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
for that disease for a minimum of 3 years are ineligible.

9. Patients must not have active infection or serious intercurrent medical illness.

10. Patients must not be pregnant/breast feeding and must agree to practice adequate
contraception.

11. Patients must not have uncontrolled hypertension (systolic >180 mm hg or diastolic >
100 mg Hg), angina pectoris, cardiac dysrhythmia, or recent (within 6 weeks)
intracranial hemorrhage.