Photodynamic Therapy (PDT) For Recurrent High Grade Gliomas

Photodynamic therapy (PDT) is a well-known treatment for other type of tumors; however it is
an experimental treatment for brain tumors. There is much we do not know about the
effectiveness of PDT in patients with brain tumors. The purpose of this study is to define
the antitumor activity of Photofrin® and laser light activation. Photofrin® is a
photosensitizing drug (a dye that is activated by light) used in PDT. We want to test the
activity of PDT and to see what are the effects (good and bad) on you and your brain tumor.
We also want to learn if this treatment will cause brain tumors to shrink and whether it will
help patients with brain tumors to live longer.

PDT is a cancer treatment that involves giving a photosensitive dye (Photofrin®), into your
vein through a tube (called an IV). This dye will go inside of the cancer cells more than it
will go inside the normal, healthy cells. PDT using Photofrin® is an approved treatment in
patients with certain types of cancer such as lung, and esophageal (from the mouth to the
stomach) cancers.

Everyone in this study will receive Photofrin® (porfimer sodium) for injection (Pinnacle
Biologics, Inc., Bannockburn, IL, USA), and be treated with red light emitted by a red laser.
The light will be sent from the laser to the surface of the brain where the tumor is located
using a light transmitting fiber. The fiber will have a knob at the end that spreads the
light out evenly in all directions.

Previous studies have shown that patients with malignant brain tumors called gliomas had a
good response to PDT. The patients in these studies lived longer than they were expected to
live. In one study of adults with brain tumors in Australia, patients given PDT had greatly
improved survival rates. Fifty seven percent (57%) of the patients with gliomas called
anaplastic astrocytoma survived for 36 months. Thirty seven percent (37%) of the patients
with gliomas called glioblastoma multiforme survived for 36 months. Froedtert Hospital, in
Milwaukee WI, has been involved in PDT studies in adults in the past. This current study is
is being done in a very similar way to the study done in Australia, and will use increased
Photofrin®) and light doses than our previous study.

Inclusion Criteria

1. Age: Greater than or equal to 18 years of age.

2. Disease: Patients with relapsed or refractory high grade glioma are eligible. Patients
must have had histologic verification of malignancy at original diagnosis or relapse.
Tumors must be supratentorial in location.

3. Disease Status: Patients must have potentially resectable disease.

4. Therapeutic Options: Patient's current disease state must be one for which there is no
known curative therapy or therapy proven to prolong survival with an acceptable
quality of life.

5. Performance Level: Karnofsky 50% or greater. Note: Neurologic deficits in patients
with CNS tumors must have been relatively stable for at least 7 days prior to study
enrollment. 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.

6. Predictable Life Expectancy: > 8weeks

7. Prior Therapy: Patients must have fully recovered from the acute toxic effects of all
prior anti-cancer chemotherapy. At least three weeks from previous chemotherapy and 4
weeks from prior radiation therapy.

8. Organ Function:

a. Adequate bone marrow function i. Absolute neutrophil count ≥ 1,000 ii. Platelet
count ≥ 100,000 (may transfuse to meet requirement) b. Adequate renal function i.
Creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73 m2 or ii. A serum creatinine
within normal range based on age/gender. c. Adequate liver function i. Bilirubin
(direct) ≤ 3X upper limit of normal (ULN) for age ii. SGPT (ALT) ≤ 10X ULN. For the
purpose of this study, the ULN for SGPT is 45 U/L.

iii. Serum albumin ≥ 2 g/dL. d. Adequate coagulation i. PT and INR ≤ 2X ULN for age.

9. Central Nervous System Function: Patients with seizure disorder may be enrolled if
receiving non-enzyme inducing anticonvulsants and well controlled.

10. Informed Consent: All patients or legally authorized representatives must sign a
written informed consent. Assent, when appropriate, will be obtained according to
institutional guidelines.

11. Archival tumor tissue slides from initial diagnosis should be reviewed by Froedtert
Health-MCW neuropathologist prior to study enrollment whenever possible.

Exclusion Criteria

1. Disseminated disease

2. Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on
this study, as risks of fetal and teratogenic adverse effects of Photofrin® are not
known.

3. Other concurrent tumor therapy

4. Subjects with porphyria

5. Subjects taking potentially photosensitizing drugs (Appendix 3)

6. The presence of adverse events of neurologic function, photosensitivity, or
photophobia Grade 4 or higher (CTCAE Version 4.02).47

7. Allergy to eggs, soybean oil, or safflower oil (due to potential allergy against
intralipids)

8. Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible.