This phase II trial studies how well nivolumab, hypofractionated stereotactic radiosurgery, and bevacizumab work in treating patients with MGMT methylated glioblastoma that has come back (recurrent). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Bevacizumab may stop or slow glioblastoma by blocking the growth of new blood vessels necessary for tumor growth. Giving nivolumab, hypofractionated stereotactic radiosurgery, and bevacizumab may work better at treating glioblastoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03743662.
PRIMARY OBJECTIVE:
I. To assess overall survival in patients with recurrent glioblastoma (first recurrence) treated with re-irradiation with concurrent bevacizumab and nivolumab followed by adjuvant nivolumab in two parallel cohorts.
SECONDARY OBJECTIVES:
I. To estimate the safety of providing radiation therapy concurrently with bevacizumab and nivolumab.
II. To assess median and 6-month progression-free survival (PFS) using the "immunotherapy response assessment in neuro-oncology" (iRANO criteria).
III. To assess objective response rate (ORR) using the iRANO criteria.
EXPLORATORY OBJECTIVES:
I. To explore the association between cytoreductive surgery and clinical outcomes, overall survival (OS) and progression free survival (PFS).
II. To assess association between genomic and immunologic biomarkers in, blood, cerebral spinal fluid (CSF), tumor tissue with clinical response.
III. To explore relationship between diffusion and perfusion parameter and clinical response.
IV. To explore association between age, Karnofsky performance status (KPS) (or Eastern Cooperative Oncology Group [ECOG] equivalent), tumor volume and radiated volume and clinical outcomes (OS and PFS).
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I (MEDICAL COHORT): Patients receive nivolumab intravenously (IV) over 30 minutes every 2 weeks. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on days 28, 42, and 56 if deemed beneficial by investigator and then every 2 weeks in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician. Starting on day 28, patients undergo 5 fractions of hypofractionated stereotactic radiosurgery every other day (Monday, Wednesday and Friday) over 2 weeks in the absence of disease progression or unacceptable toxicity.
COHORT II (SURGICAL COHORT): Patients receive nivolumab IV over 30 minutes every 2 weeks and undergo surgery at day 14. Treatment with nivolumab repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients may also receive bevacizumab IV on days 42 and 56 if deemed beneficial by investigator and then every 2 weeks in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician. Starting on day 28, patients undergo 5 fractions of hypofractionated stereotactic radiosurgery every other day (Monday, Wednesday and Friday) over 2 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for a minimum of 1 year.
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorChristian Grommes
