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

NCT ID: NCT00544817

Last Updated: 2016-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2010-08-31

Brief 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.

Detailed Description

All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.

Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.

After completion of combined modality therapy, patients will have 4 weeks without any therapy.

Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide

Conditions

Glioblastoma Multiforme

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination Therapy

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Group Type: EXPERIMENTAL

Radiation Therapy

Intervention Type: RADIATION

2 Gy/fraction, single daily fractions M-F, to 60 Gy total

Temozolomide

Intervention Type: DRUG

In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily

In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles

Sorafenib

Intervention Type: DRUG

In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months

Interventions

Radiation Therapy

2 Gy/fraction, single daily fractions M-F, to 60 Gy total

Intervention Type: RADIATION

Temozolomide

In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily

In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles

Intervention Type: DRUG

Sorafenib

In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months

Intervention Type: DRUG

Other Intervention Names

Temodar; Nexavar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John D. Hainsworth, M.D.

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

Florida Cancer Specialists

Fort Myers, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Grand Rapids Clinical Oncology Program

Grand Rapids, Michigan, United States

Methodist Cancer Center

Omaha, Nebraska, United States

Oncology Hematology Care

Cincinnati, Ohio, United States

Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Tennessee Oncology

Nashville, Tennessee, United States

South Texas Oncology and Hematology

San Antonio, Texas, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Countries

United States

References

Hainsworth JD, Ervin T, Friedman E, Priego V, Murphy PB, Clark BL, Lamar RE. Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme. Cancer. 2010 Aug 1;116(15):3663-9. doi: 10.1002/cncr.25275.

Reference Type: RESULT

PMID: 20564147 (View on PubMed)

Other Identifiers

SCRI CNS 09

Identifier Type: -

Identifier Source: org_study_id