Subventricular Zone (SVZ) and Temozolomide in Glioblastoma Multiforme

There is pre-clinical data to suggest that neural progenitor cells in the subventricular zone
may play a role in glioblastoma recurrence. Retrospective studies in humans suggest
potentially improved survival in patients who received high doses of radiation to the
subventricular zone when compared with patients who received lower radiation doses to this
area. The purpose of this study is to prospectively examine progression free survival in
patients with newly diagnosed glioblastoma treated with adjuvant temozolomide plus a
radiation treatment plan which intentionally prescribes radiation dose to both the tumor and
the subventricular zone compared to patients treated with standard radiation therapy. 3
patients out of every 4 will be treated with the modified study radiation treatment and 1
patient out of every 4 will received a more standard radiation treatment plan.

Inclusion Criteria:

- Patient must have newly diagnosed, histologically confirmed GBM.

- Patient must have undergone gross total resection, subtotal resection, or biopsy with
the extent of resection determined by the treating neurosurgeon, and must begin
radiation within 12 weeks of this procedure.

- Patients must not have received previous irradiation to the brain.

- Patient must be at least 18 years of age since the diagnosis of GBM in patients
younger than 18 is rare and accurate evaluation of neurocognitive function would
require a different battery of examinations than employed in this study.

- ECOG performance status 0-2 (Karnofsky >60%; see Appendix A).

- Patient must be scheduled to receive temozolomide concurrent with and following
radiation (temozolomide may be started late due to insurance reasons, insufficient
counts, or other reasons).

- If a woman is of child-bearing potential, a negative urine or serum pregnancy test
must be demonstrated prior to treatment. Women of childbearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) for the duration of study participation and for up to 12 weeks following
the study. Should a women become pregnant or suspect she is pregnant while
participating in this study she should inform her treating physician immediately.

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

- All patients must be informed of the investigational nature of this study and must be
given written informed consent in accordance with institutional and federal
guidelines.

- Radiation therapy must begin within 12 weeks of surgery.

Exclusion Criteria:

- No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, cervical carcinoma in situ, or other cancer from which the patient
has been disease free for at least 2 years.

- Patients with uncontrolled intercurrent illness including, but not limited to, ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements will be excluded.

- Pregnant and breastfeeding women are excluded. Women of child-bearing potential who
are unwilling or unable to use an acceptable method of birth control to avoid
pregnancy for the entire study period and up to 12 weeks after the study are excluded.
This applies to any woman who has not experienced menarche and who has not undergone
successful surgical sterilization or is not postmenopausal (defined as amenorrhea for
at least 12 consecutive months). Male subjects must also agree to use effective
contraception for the same period as above.

- Use of Avastin or another VEG-F inhibitor prior to progression is not permitted.