A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme

Inclusion Criteria:

1. Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).

2. Patients who have had partial or complete surgical debulking are eligible, as are
those with inoperable glioblastoma.

3. No previous treatment for glioblastoma except for previous surgical debulking (i.e.
no previous radiotherapy, local chemotherapy, or systemic therapy).

4. ECOG performance status 0 or 1 (See Appendix C)

5. Age ≥ 18 years

6. Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥
100,000/μL.

7. Adequate liver function

- Total bilirubin ≤ 1.5 x ULN

- ALT and AST ≤ 2.5 x ULN

8. Serum creatinine < 1.5 x ULN

9. Women of child-bearing potential must have a negative serum pregnancy test performed
within 7 days prior to the start of treatment. Women must agree to not breast feed
while receiving study treatment.

10. Women of child-bearing potential and men must agree to use adequate contraception
(barrier method of birth control) while receiving study treatment. Women should use
adequate birth control for at least 3 months after the last administration of
sorafenib.

11. INR < 1.5 or PT/PTT within normal limits in patients not receiving anticoagulation.
However, patients receiving anticoagulation treatment with an agent such as warfarin
or heparin are also eligible. For patients on warfarin, the INR should be measured
prior to initiation of sorafenib and monitored at least weekly, or as defined by the
local standard of care, until INR is stable.

12. Patients must have the ability to understand and the willingness to sign written
informed consent. A signed informed consent must be obtained prior to any
study-specific procedures.

Exclusion Criteria:

1. Patients must have the ability to swallow whole pills.

2. Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D);
unstable angina or new onset angina within the last 3 months; myocardial infarction
within the last 6 months.

3. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

4. Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic
pressure > 90mm Hg, despite optimal medical management

5. Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
infection

6. Active clinically serious infection > grade 2

7. Thrombotic or embolic events including cerebral vascular accident or TIAs within the
past 6 months

8. Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of
sorafenib

9. Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of
sorafenib

10. Serious non-healing wound, ulcer, or bone fracture

11. Evidence or history of bleeding diathesis or coagulopathy

12. Major surgery, open biopsy, or significant traumatic injury within 4 weeks of
beginning treatment with sorafenib

13. Use of St. John's Wort or rifampicin

14. Known or suspected allergy to sorafenib or temozolomide

15. Any malabsorption problem

16. Other active malignancies, or treatment for invasive cancer within the last 2 years