RTOG Opens Phase III Trial of Temozolomide and Radiotherapy Plus Bevacizumab for Newly Diagnosed Glioblastoma Tumors
The Radiation Therapy Oncology Group (RTOG) has opened a new phase III trial for patients with newly diagnosed glioblastoma (GBM) to determine if the addition of bevacizumab to the current standard-of-care therapy, concurrent chemoradiation and adjuvant temozolomide, improves patient outcomes. RTOG is a National Cancer Institute-funded national clinical trials group and is administered by the American College of Radiology.
“Prior studies have shown that patients with methylated MGMT are more likely to respond to temozolomide-based therapy. Since encouraging response rates have been demonstrated in phase II trials of Avastin for treatment in patients with recurrent glioblastoma, we designed this trial as a natural progression to evaluate the benefits of the combination therapy in newly diagnosed GBM,” said Mark R. Gilbert, MD, the study’s principal investigator and professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center. “The goal of RTOG 0825 is to demonstrate improvements in progression-free and overall survival in all GBM patients being treated with the combination therapy versus temozolomide/radiation therapy alone.”
Patients enrolled in the new trial, RTOG 0825, will have histologic confirmation and analysis of their MGMT status through central pathology review after registration on the study but prior to treatment assignment. All patients will receive standard therapy of radiation and daily temozolomide for three weeks. Patients will then be stratified by MGMT methylation status and molecular profile to receive either standard therapy plus bevacizumab or a continuation of their standard therapy plus placebo. RTOG investigators will examine progression-free and overall survival rates, tumor molecular profiles for prognostic factors, neurocognitive function, health-related quality of life, patient-reported outcomes, treatment side-effects, and the interactions between these factors.
“This study is an exciting continuation of our pivotal research in glioblastoma. RTOG recently completed a study of standard versus dose-intensive temozolomide combined with radiotherapy for this patient group,” said Walter J. Curran, Jr., M.D., the RTOG Group Chair, and the Lawrence W. Davis Professor and Chair of the Department of Radiation Oncology in the Emory School of Medicine and Chief Medical Officer of the Emory Winship Cancer Institute. “We rapidly accrued over 1000 patients to that study and we are looking forward to the enthusiastic support of the oncology community for this new study.”
RTOG 0825 will enroll 720 patients with histopathologically confirmed glioblastoma from RTOG member institutions in North America and internationally. Members of the North Central Cancer Treatment Group (NCCTG) and the Eastern Cooperative Oncology Group (ECOG) will also participate in this study. The protocol is available at: http://www.rtog.org/members/protocols/0825/0825.pdf.
About Glioblastoma Multiforme (GBM) Brain Tumors
GBM is the most aggressive and malignant form of glioma, a type of primary brain tumor. The annual incidence of GBM is four to five cases per 100,000 persons, with 25,000 to 28,000 new cases diagnosed each year in North America and Europe.
About OncoMethylome Sciences' MGMT Assay
The use of OncoMethylome’s MGMT assay is based on studies that have shown that methylation (silencing) of the MGMT gene promoter may help to identify brain tumors more likely to respond to standard chemotherapeutic agents. Following treatment, GBM patients whose tumors are positive for MGMT gene promoter methylation have demonstrated improved overall survival when compared to patients with unmethylated or normally functioning MGMT. The MGMT assay was used in a retrospective analysis of a subset of GBM patients in a study published in The New England Journal of Medicine in March 2005 (N Engl J Med 2005; 532; 997-1003). Prospective confirmation of the predictive value of MGMT gene promoter methylation for the treatment with radiotherapy and temozolomide is currently ongoing within a large randomized international phase III trial (RTOG 0525-EORTC26052-22053).
About Bevacizumab (Avastin®)
Bevacizumab (Avastin®) is a biologic antibody designed to specifically inhibit the vascular endothelial growth factor (VEGF) protein that plays an important role in the development and maintenance of blood vessels, a process known as angiogenesis. Glioblastomas express high levels of VEGF and develop an extensive network of tumor blood vessels. VEGF is a potent activator of angiogenesis throughout the lifecycle of a tumor and is thought to be critical to a tumor's ability to grow beyond a few millimeters.
Avastin is approved for the first- and second-line treatment of metastatic colorectal cancer in combination with intravenous 5-FU-based chemotherapy and for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel. Avastin is also approved, in combination with paclitaxel, for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. Please visit www.gene.com for full prescribing information, including Boxed WARNINGS, side effects, and important safety information.
