Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme

• Status: Completed
• Trial end date: 2010-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).

In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: SCRI Development Innovations, LLC
• Collaborator: Bayer
• Treatments: Dacarbazine; Niacinamide; Sorafenib; Temozolomide

Criteria

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