A Phase II Open Label, Randomized Study Testing the Efficacy of Retifanlimab in Combination with Bevacizumab and Hypofractionated Radiotherapy in Patients with Recurrent GBM
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
• Dexamethasone dose ≤ 4mg daily at the time of randomization (higher dose of steroid for symptom control is allowed during the study)
• Karnofsky performance status ≥ 60%
• Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3 (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the Academic and Community Cancer Research Untied (ACCRU) website under General Forms
• Platelet count ≥ 100,000/mm\^3 (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the ACCRU website under General Forms
• Hemoglobin ≥ 9.0 g/dL (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the ACCRU website under General Forms
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the ACCRU website under General Forms
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the ACCRU website under General Forms
• Creatinine ≤ 1.5 x ULN (obtained ≤ 28 days prior to registration)
‣ NOTE: If your site laboratory reports use different units of measurement than what is required by the protocol eligibility requirements, please use the Lab Test Unit Conversion Worksheet available on the ACCRU website under General Forms
• Negative pregnancy test done ≤ 14 days prior to registration for women of childbearing potential only. (Pregnancy test can be urine or serum.)
‣ NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
⁃ A female of childbearing potential is a sexually mature female who:
• 1\) Has not undergone a hysterectomy or bilateral hysterectomy; or
∙ 2\) Has not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time in the preceding 12 consecutive months)
• Provide informed written consent ≤ 28 days prior to registration
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study, i.e., active treatment)
• Willing to provide mandatory blood specimens for correlative research purposes