Last updated on June 2019

Nivolumab Plus Standard Dose Bevacizumab Versus Nivolumab Plus Low Dose Bevacizumab in GBM


Brief description of study

The purpose of this study is to test the effectiveness (how well the drug works), safety and tolerability of an investigational drug called nivolumab (also known as BMS-936558) in glioblastoma (a malignant tumor, or GBM), when added to bevacizumab.

Nivolumab is an antibody (a kind of human protein) that is being tested to see if it will allow the body's immune system to work against glioblastoma tumors. Opdivo (Nivolumab) is currently FDA approved in the United States for melanoma (a type of skin cancer), non-small cell lung cancer, renal cell cancer (a type of kidney cancer), Hodgkin's lymphoma but is not approved in glioblastoma. Nivolumab may help your immune system detect and attack cancer cells.

Bevacizumab is a drug which works on the blood vessel that supply the tumor and potentially can starve the tumor by cutting off the blood supply to these tumors. Bevacizumab is commercially available and FDA approved for patients with recurrent glioblastoma.

This study has two study groups. Arm 1 will receive the study drug Nivolumab 240mg and bevacizumab 10 mg (standard dose) every 2 weeks and Arm 2 will receive the study drug Nivolumab 240 mg and bevacizumab 3 mg (reduced dose) every 2 weeks. A process will be used to assign patients, by chance, to one of the study groups. Neither patients nor doctors can choose which group patients are in. This is done by chance because no one knows if one study group is better or worse than the other. 90 total patients are expected to participate in this study (45 patients in each arm).

Your total participation in this study from the time you have signed the informed consent to your last visit, including follow-up visits, may be more than three years (depending on what effect the treatment has on your cancer, and how well you tolerate the treatment).

Detailed Study Description

Primary Endpoint(s) To evaluate the efficacy of nivolumab when administered with standard and reduced bevacizumab dosing among recurrent glioblastoma patients as measured by the rate of overall survival at twelve months.

Secondary Endpoint(s) To evaluate the safety and tolerability of nivolumab in combination with bevacizumab administered according to standard and reduced dosage schedules for recurrent glioblastoma patients.

To compare progression free survival (PFS) at 6 months of nivolumab when administered with standard and reduced bevacizumab dosing for recurrent glioblastoma patients.

To compare the overall survival rate of nivolumab when administered with standard and reduced bevacizumab dosing for recurrent glioblastoma patients.

To compare progression free survival (PFS) of when administered with standard and reduced bevacizumab dosing for recurrent glioblastoma patients.

To compare the objective response rate (ORR) of nivolumab and bevacizumab administered according to standard and reduced dosage schedules for recurrent glioblastoma patients

Exploratory Endpoints (s) To evaluate whether baseline values or subsequent changes in circulating immunologic parameters (including but not limited to the number of T-cells, B-cells and natural killer (NK) cells; the number of T cell subsets; soluble circulating cytokines) are associated with outcome.

To assess neurologic functioning in the treatment arms using the Neurologic Assessment in Neuro-Oncology (NANO).

To assess the perfusion and diffusion base imaging to correlate with changes and response to nivolumab when administered with standard and reduced bevacizumab dosing.

To assess response using the immunotherapy response assessment in neuro-oncology criteria relative to survival.

Study design and duration This is a randomized, open-label, phase 2 safety study of nivolumab and bevacizumab administered according to standard and reduced dosage schedules in adult ( 18 years) subjects with a first recurrence or second recurrence of glioblastoma (GBM). Subjects must have received previous treatment with radiotherapy and may have up to 2 recurrences. Patients will undergo 1:1 randomization to receive treatment with either nivolumab (240 mg flat dosing IV every 2 weeks) and bevacizumab administered according to standard (10 mg/kg IV every 2 weeks; Arm A) and reduced (3 mg/kg IV every 2 weeks; Arm B) dosage schedules for recurrent glioblastoma patients. The study will allow patients that require decadron up to 4 mg/ day to participate in the study.

Clinical Study Identifier: NCT03452579

Find a site near you

Start Over