Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
Information source: Sarah Cannon Research Institute
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Glioblastoma Multiforme
Intervention: Radiation therapy, temozolomide and sorafenib (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Sarah Cannon Research Institute Official(s) and/or principal investigator(s):
John D. Hainsworth, M.D., Study Chair, Affiliation: SCRI Oncology Research Consortium
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.
Clinical Details
Official title: 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
Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Primary outcome: Feasibility, toxicity, efficacy, and be progression-free survival.
Secondary outcome: Overall survival and objective response rate
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
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Florida Cancer Specialists, Fort Myers, Florida 33901, United States
Northeast Georgia Medical Center, Gainesville, Georgia 30501, United States
Center for Cancer and Blood Disorders, Bethesda, Maryland 20817, United States
Grand Rapids Clinical Oncology Program, Grand Rapids, Michigan 49503, United States
Methodist Cancer Center, Omaha, Nebraska 68114, United States
Oncology Hematology Care, Cincinnati, Ohio 45242, United States
Spartanburg Regional Medical Center, Spartanburg, South Carolina 29303, United States
Tennessee Oncology, Nashville, Tennessee 37203, United States
South Texas Oncology and Hematology, San Antonio, Texas 78258, United States
Virginia Cancer Institute, Richmond, Virginia 23235, United States
Additional Information
Starting date: April 2007
Ending date: April 2009
Last updated: June 17, 2008
|
