Tumor Resection and Gliadel® Wafers, Followed by Temodar® With Standard Radiation or GammaKnife® for New GBM

The primary purpose of this study is to determine if single fraction GK radiosurgical
treatment to the resection bed can achieve equivalent local control and survival for
patients with GBM after GTR, Gliadel® implant and temozolomide therapy compared to patients
receiving standard postoperative RT with temozolomide, but offer improved quality of life
and preserve cognitive function.

In Phase I, it is proposed that 20 patients with newly diagnosed glioblastoma multiforme
(GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to
the resection cavity at that time will be eligible for study. These patients will then
receive Gamma Knife® (GK) radiosurgery to the resection cavity margin within 4 weeks
following surgical resection and within 24 hours of starting temozolomide (Temodar®)
induction therapy. Temozolomide (Temodar®) maintenance therapy would be administered for 12
months.

In Phase II, it is proposed that 60 patients with newly diagnosed glioblastoma multiforme
(GBM) undergo gross total resection (GTR) with Gliadel® (carmustine) wafer implantation to
the resection cavity at the time of initial resection will be eligible for study. These
patients will then be randomized to either standard fractionated conformal radiation therapy
(RT) or Gamma Knife® (GK) radiosurgery to the resection cavity margin. Fractionated RT would
be administered with concurrent temozolomide Gamma knife® radiosurgery to the resection
cavity margin will be administered within 24 hours of starting temozolomide induction
therapy. Both the GK and RT will be administered within 4 weeks following surgical
resection. Temozolomide (Temodar®) maintenance therapy would be administered to all patients
in both arms of the study for 12 months.

It is believed that all patients will benefit from enrollment in the study regardless of the
treatment arm to which they are randomized. All patients will be receiving focally
aggressive surgical resection with Gliadel® implant in addition to temozolomide for
prevention of both focal and distant recurrence.

Patients who are randomized to receive GK radiosurgical treatment to the resection bed
margin may benefit from increased local control based on a prior non-randomized study.
However these patients will be treated in a non-standard fashion and may be subjected to a
higher incidence of focal radiation necrosis or a higher incidence of failure beyond the
resection margin compared to standard patients.

The GK treated patients however, will be spared the standard 6 weeks of RT postoperatively.
It is hypothesized that those receiving GK will therefore have an improved quality of life
with respect to having less fatigue, lack of hair loss and a decreased incidence of delayed
cognitive decline associated with standard RT.

Inclusion Criteria:

- single enhancing lesion of the brain with MRI appearance consistent with GBM

- Must be appropriate for Gliadel® wafer implant

- Pathologic confirmation of GBM

- no gross residual tumor found on the immediate postoperative MRI scan

- Volumetric measurements of the resection cavity margin being < 50 cc

- Karnofsky performance status (KPS) 80% or better

- Must be able to undergo MRI imaging with gadolinium

- Willingness to have follow up visits at Barrow Neurological Institute(BNI)

Exclusion Criteria:

- multi-focal tumors

- tumors which extend across the corpus callosum,

- residual nodular disease

- Tumors, with a contraindication to Gliadel® implant, such as an anticipated extensive
ventricular opening resulting from complete resection.

- Tumor measuring greater than 50cc in volume (on post-operative scan) Volume < 50 cc
if volume if a significant volume of eloquent tissue is included in the proposed
treatment volume

- Unable to undergo MRI with gadolinium

- History of cancer within 2 years of GBM diagnosis (basal and squamous cell skin
cancers are allowed)

- Patient is not willing to follow up at BNI