Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
|ClinicalTrials.gov Identifier: NCT00544817|
Recruitment Status : Completed
First Posted : October 16, 2007
Results First Posted : December 13, 2012
Last Update Posted : September 1, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma Multiforme||Radiation: Radiation Therapy Drug: Temozolomide Drug: Sorafenib||Phase 2|
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||April 2007|
|Actual Primary Completion Date :||June 2008|
|Actual Study Completion Date :||August 2010|
Experimental: 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
Radiation: Radiation Therapy
2 Gy/fraction, single daily fractions M-F, to 60 Gy totalDrug: 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
Other Name: TemodarDrug: Sorafenib
In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
Other Name: Nexavar
- Progression-free Survival [ Time Frame: 18 months ]Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
- Overall Survival [ Time Frame: 18 months ]Defined as Day 1 of protocol treatment to date of death from any cause.
- Objective Response [ Time Frame: every 8 weeks until disease progression, estimated 18 months ]
The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria.
The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD).
CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved.
PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved.
SD: does not qualify for complete response, partial response or progression. Clinically stable.
PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00544817
|United States, Florida|
|Florida Cancer Specialists|
|Fort Myers, Florida, United States, 33901|
|United States, Georgia|
|Northeast Georgia Medical Center|
|Gainesville, Georgia, United States, 30501|
|United States, Maryland|
|Center for Cancer and Blood Disorders|
|Bethesda, Maryland, United States, 20817|
|United States, Michigan|
|Grand Rapids Clinical Oncology Program|
|Grand Rapids, Michigan, United States, 49503|
|United States, Nebraska|
|Methodist Cancer Center|
|Omaha, Nebraska, United States, 68114|
|United States, Ohio|
|Oncology Hematology Care|
|Cincinnati, Ohio, United States, 45242|
|United States, South Carolina|
|Spartanburg Regional Medical Center|
|Spartanburg, South Carolina, United States, 29303|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|South Texas Oncology and Hematology|
|San Antonio, Texas, United States, 78258|
|United States, Virginia|
|Virginia Cancer Institute|
|Richmond, Virginia, United States, 23235|
|Study Chair:||John D. Hainsworth, M.D.||SCRI Development Innovations, LLC|