Nivolumab Plus Standard Dose Bevacizumab Versus Nivolumab Plus Low Dose Bevacizumab in GBM
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|ClinicalTrials.gov Identifier: NCT03452579|
Recruitment Status : Recruiting
First Posted : March 2, 2018
Last Update Posted : May 14, 2018
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).
|Condition or disease||Intervention/treatment||Phase|
|Glioblastoma||Drug: Nivolumab Drug: Standard Dose Bevacizumab Drug: Reduced Dose Bevacizumab||Phase 2|
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.
|Study Type :||Interventional|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||CA209-382 A Randomized Phase 2 Open Label Study of Nivolumab Plus Standard Dose Bevacizumab Versus Nivolumab Plus Low Dose Bevacizumab in Recurrent Glioblastoma (GBM)|
|Actual Study Start Date :||May 10, 2018|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Active Comparator: Nivolumab + Standard Dose Bevacizumab
nivolumab 240 mg and standard dose bevacizumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity
Other Name: Opdivo
Drug: Standard Dose Bevacizumab
Other Name: Avastin
Experimental: Nivolumab + Reduced Dose Bevacizumab
nivolumab 240 mg and reduced dose bevacizumab 3mg/kg every 2 weeks until disease progression or unacceptable toxicity
Other Name: Opdivo
Drug: Reduced Dose Bevacizumab
Other Name: Avastin
- Overall Survival at 12 Months [ Time Frame: Up to 12 months after beginning therapy ]The proportion of subjects in the analysis population who remain alive for at least twelve months following initiation of study therapy.
- Overall Survival [ Time Frame: Up to 3 years after beginning treatment ]Time from beginning of treatment to death
- Overall Response Rate [ Time Frame: Up to 3 years after beginning treatment ]Proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using Radiologic Assessment in Neuro-Oncology criteria (RANO) criteria.
- Duration of Response [ Time Frame: Up to 3 years after beginning treatment ]Time from first RANO response to disease progression in subjects who achieve a PR or better
- Progression-Free Survival [ Time Frame: Up to 3 years after beginning treatment ]Defined as the time from allocation to the first documented disease progression according to RANO or death due to any cause, whichever occurs first
- Progression-Free Survival at Six Months [ Time Frame: Up to six months after beginning treatment ]The proportion of subjects in the analysis population who remain progression-free for at least six months following initiation of study therapy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03452579
|Contact: Manmeet Ahluwalia, MDemail@example.com|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Not yet recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: David A Reardon, MD 617-632-4750 David_Reardon@DFCI.harvard.edu|
|Principal Investigator: David A Reardon, MD|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Manmeet Ahluwalia, MD 216-444-6145 firstname.lastname@example.org|
|Principal Investigator: Manmeet Ahluwalia, MD|
|Principal Investigator:||Manmeet Ahluwalia, MD||Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center|