This phase II trial tests how well retifanlimab with bevacizumab and hypofractionated radiotherapy, compared to bevacizumab and hypofractionated radiotherapy alone, works in treating patients with glioblastoma that has come back after a period of improvement (recurrent). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving retifanlimab with bevacizumab and hypofractionated radiotherapy may work better in treating patients with recurrent glioblastoma than bevacizumab and hypofractionated radiotherapy alone.
Age ≥ 18 years
Recurrent World Health Organization (WHO) grade IV glioblastoma. Note: Any number of recurrences are allowable. Glioblastoma (GBM) variants and molecular GBM are allowed
Candidates for radiotherapy
Prior use of bevacizumab is allowed as long as the last treatment is > 4 months prior to randomization
Pregnant persons
Nursing persons
Persons of childbearing potential who are unwilling to employ adequate contraception (men and women)
Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Parallel
Bevacizumab
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT
Electronic Health Record Review
Other interventionAncillary studies
Hypofractionated Radiation Therapy
RadiationUndergo radiation therapy
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Retifanlimab
Biological/VaccineGiven IV
Overall survival (OS)
Defined as the proportion of patients who are alive 9 months after randomization based on Kaplan Meier estimate. The proportion of patients alive will be compared between treatment arms using a z-score test statistic. The 9-month OS Kaplan Meier estimate and corresponding 95% confidence interval for each arm will be reported.
OS
Overall survival is defined as the time from registration to death from any cause. OS will be estimated using the Kaplan-Meier method. The logrank test will be used to compare the distribution between treatment arms. The median OS and corresponding 95% confidence interval (by Brookmeyer and Crowley) will be reported for each treatment arm.
Progression free survival (PFS)
Progression free survival is defined as the time from randomization to documentation of disease progression or death due to any cause, whichever is first. The distribution of PFS will be estimated using the method of Kaplan-Meier. PFS will be compared between the 2 treatment arms using the log-rank test. The median PFS and corresponding 95% confidence intervals will be reported.
Objective response rate (ORR)
Objective response is defined as experiencing a complete response (CR) or partial response (PR) (as defined by RANO criteria, see section 11.0) while on protocol treatment. Objective response rate (ORR) is defined as the number of patients who experience objective response divided by the number of patients in the primary analysis population. ORR will be compared between the 2 treatment arms. Confidence intervals for ORR will be calculated according to the approach of Clopper and Pearson. Overall response rate and the corresponding 95% confidence interval will be reported.
Neurologic function domain scores
Neurologic function domain scores of the Neurologic Assessment in Neuro-Oncology be summarized by descriptive statistics including mean, median, standard deviation, and range for each regimen at each time point. The difference between baseline and 2 months (1st restaging scan) will be compared using a Wilcoxon Rank Sum test across arm for each domain. The median difference for each domain and 1st and 3rd quartile will be reported for each arm.
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Academic and Community Cancer Research United
Lead sponsor
National Cancer Institute (NCI)
Collaborator
