Randomized Phase II Trial of Concurrent Bevacizumab and Re-Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma

Radiation Therapy Oncology Group31 sites in 1 country182 target enrollmentDecember 20, 2012

ConditionsAdult Giant Cell Glioblastoma Adult Glioblastoma Adult Gliosarcoma Recurrent Adult Brain Tumor

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Adult Giant Cell Glioblastoma
Sponsor: Radiation Therapy Oncology Group
Enrollment: 182
Locations: 31
Primary Endpoint: Overall Survival
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This randomized phase II trial studies how well bevacizumab with or without radiation therapy works in treating patients with recurrent glioblastoma. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet know whether bevacizumab is more effective with or without radiation therapy in treating patients with recurrent glioblastoma

Detailed Description

PRIMARY OBJECTIVES: I. To establish an improvement in overall survival in recurrent glioblastoma (GBM) patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone. SECONDARY OBJECTIVES: I. To estimate and compare the rate of objective response in patients with measurable disease. II. To estimate and compare the 6-month progression-free survival rate. III. To estimate and compare progression-free survival. IV. To estimate and compare the rate of treatment adverse events. V. To estimate and compare the rate of grade 3+ acute or delayed central nervous system (CNS) toxicity. OUTLINE: Patients are randomized to 1 of 2 treatment arms. In both arms, courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 1 year and then annually thereafter.

Registry

clinicaltrials.gov

Start Date

December 20, 2012

End Date

December 22, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Radiation Therapy Oncology Group

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histopathologically proven diagnosis of glioblastoma or variants (gliosarcoma, giant cell glioblastoma etc); patients will be eligible if the original histology was lower-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma is made
•Patients who did not have recent surgery for their glioblastoma must have shown unequivocal radiographic evidence for tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan (or computed tomography \[CT\] scan for patients with non-compatible devices) CT scan within 21 days prior to registration.
•\* Note: Patients who did have surgery with a post-operative contrast-enhance scan falling outside the 5 week window prior to registration, must have a repeat MRI scan (or CT scan for patients with non-compatible devices) within 21 days prior to registration.
•Patients also must have passed an interval of 6 months or greater between completion of prior radiotherapy and registration; if patients have not passed an interval of at least 6 months, they may still be eligible if they meet one or more of the following criteria:
•New areas of tumor outside the original radiotherapy fields as determined by the investigator, or
•Histologic confirmation of tumor through biopsy or resection, or
•Nuclear medicine imaging, magnetic resonance (MR) spectroscopy, or MR perfusion imaging consistent with true progressive disease, rather than radiation necrosis obtained within 28 days of registration AND an interval of at least 90 days between completion of radiotherapy and registration
•Patients unable to undergo MR imaging because of non-compatible devices can be enrolled provided CT scans are obtained and are of sufficient quality; patients without non-compatible devices may not use CT scans performed to meet this requirement
•Prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses
•Patients who have received prior treatment with non-standard radiation therapy (RT) dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible

Exclusion Criteria

•More than three relapses
•Infratentorial or leptomeningeal evidence of recurrent disease
•Recurrent or persistent tumor greater than 6 cm in maximum diameter
•Prior therapy with an inhibitor of vascular endothelial growth factor (VEGF) or VEGFR (including bevacizumab)
•Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1 year (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
•Severe, active co-morbidity, defined as follows:
•Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months prior to registration
•Transmural myocardial infarction within the last 6 months prior to registration
•History of stroke or transient ischemic attack within 6 months prior to registration
•Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease

Outcomes

Primary Outcomes

Overall Survival

Time Frame: From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.

Survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times will be compared between the arms, which is reported in the statistical analysis results. Eighteen-month rates are provided. Analysis was planned to occur when 135 deaths were reported.

Secondary Outcomes

Percentage of Participants With Complete or Partial Best Response(From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.)
Percentage of Participants Progression-free at 6 Months(From randomization to six months)
Progression-free Survival(From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.)
Number of Participants With Grade 3+ CNS Toxicity More Than 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment(From 91 days after the start of radiation therapy to end of follow-up. Maximum follow-up at the time of analysis is 58.2 months.)
Percentage of Participants With Grade 3+ Central Nervous System (CNS) Toxicity Within 90 Days of Start of Radiation Therapy Reported as Possibly/Probably/Definitely Related to Protocol Treatment(From randomization to last follow-up. Maximum follow-up at time of analysis was 52.8 months.)