The purpose of this study is to find the benefits of combining nivolumab with metformin in advanced non-small cell lung cancer with and without prior treatment with immunotherapy. We will also be looking at the safety of the combination. Nivolumab is currently approved in certain cancers such as melanoma, lung cancer and kidney cancer. Metformin is approved by the US Food and Drug Administration (FDA) to treat diabetes. In this study, Metformin is being used to treat cancer. This use is not approved by the FDA; therefore, in this study, it is considered experimental. Experimental means the U.S. FDA has not approved the drug for use in your type of cancer. Nivolumab is an antibody (a human protein that sticks to a part of the tumor and/or immune cells) designed to allow the body's immune system to work against tumor cells. It is believed that metformin has immune modifying properties, meaning it can boost your immune system. As a result, it may help certain cancer treatments, known as immunotherapy, to work better.
PRIMARY OBJECTIVES: I. To assess anti-tumor activity of the combination treatment of metformin hydrochloride (metformin) with nivolumab in patients with non-small cell lung cancer with and without prior exposure to PD-1/PD-L1 inhibitors. SECONDARY OBJECTIVES: I. To assess the efficacy of the combination treatment of metformin with nivolumab according to depth, duration, and persistence of response, disease control rate (DCR; complete response \[CR\], partial response \[PR\], and stable disease \[SD\] at 24 weeks), progression-free survival (PFS), and overall survival (OS) in patients with non-small cell lung cancer with and without prior exposure to PD-1/PD-L1 inhibitors using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version (v)1.1. II. To assess the efficacy of the combination treatment of metformin with nivolumab according to depth, duration, and persistence of response, objective response rate (ORR), DCR, PFS, and OS in the above population using immune-related RECIST (irRECIST) criteria. III. To assess the safety and tolerability profile of the combination treatment of metformin with nivolumab in the above population using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. TERTIARY OBJECTIVES: I. To assess the immune-related tumor and blood biomarkers including T cell markers and their association with treatment response in the above population. II. To assess the dynamic change in both immune and genomic biomarkers in blood that may correlate with response to metformin. OUTLINE: Patients receive metformin hydrochloride orally (PO) once daily (QD) on days -7 to -1 and 1-28. Patients also receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15 of courses 1-4, then over 60 minutes on day 1 beginning course 5. Courses repeat every 28 days in the absence of disease progression, unacceptable toxicity, or withdrawal of consent. After completion of study treatment, patients are followed up for 30 days, every 3 months for 1 year, then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
17
Northwestern University
Chicago, Illinois, United States
Northwestern University- Lake Forest Hospital
Lake Forest, Illinois, United States
Objective Response Rate (ORR) of Patients With Non-small Cell Lung Cancer Treated With Nivolumab and Metformin Combination Using RECIST 1.1
Anti-tumor activity will be assessed by ORR (defined as the sum of Complete Responses (CR) and/or Partial Responses (PR)) as measured by CT or MRI scan approximately every 8 weeks and assessed by Response Evaluation Criteria in Solid Tumors, RECIST criteria v1.1 using the patients best response to treatment where: CR=Disappearance of all lesions PR=At least a 30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum diameters
Time frame: up to a maximum of 24 weeks from start of treatment (Range of cycles that best response was seen was 2-5 cycles of treatment where 1 cycle =28 days)
Depth of Response
Depth of response (stable disease or partial response) defined as the change in the sum of the largest tumor diameters per RECIST v1.1 and irRECIST criteria.
Time frame: 24 weeks from start of treatment
Duration of Response
Duration of response will be evaluated using RECIST v1.1 and irRECIST criteria.
Time frame: Up to 3 years
Persistence of Response
Persistence of response will be assessed using RECIST v1.1 and irRECIST criteria.
Time frame: Up to 3 years
Disease Control Rate (DCR)
DCR will be evaluated using RECIST v1.1 and irRECIST criteria.
Time frame: 24 weeks from start of treatment
Progression-Free Survival (PFS)
PFS will be assessed using RECIST v1.1 and irRECIST criteria.
Time frame: At 1 year than at 2 years
Overall Survival (OS)
OS will be assessed using RECIST v1.1 and irRECIST criteria.
Time frame: At 1 year than at 2 years
Objective Response Rate (ORR) of Patients With Non-small Cell Lung Cancer Treated With Nivolumab and Metformin Combination Using irRECIST.
Anti-tumor activity will be assessed by ORR (defined as the sum of Complete Responses (CR) and/or Partial Responses (PR)) as measured by CT or MRI scan approximately every 8 weeks and assessed by irRECIST criteria using the patients best response to treatment where: CR=Disappearance of all lesions PR=At least a 30% decrease in the sum of the diameters of the target lesions, taking as reference the baseline sum diameters But also new measurable lesions are incorporated in the tumor burden, which is used to determine immune-related progressive disease (irPD), immune-related partial response (irPR), and immune-related complete response (irCR). New non-measurable lesions preclude irCR. Under RECST v1.1, there is no confirmation for PD. Under irRECIST, responses and irPDs must be confirmed by consecutive scans at least 4 weeks apart, assuming no clinical deterioration.
Time frame: up to a maximum of 24 weeks from start of treatment (Range of cycles that best response was seen was 2-6 cycles of treatment where 1 cycle =28 days)
Incidence of Adverse Events
Assess the safety and tolerability of the combination treatment of metformin with nivolumab by evaluating the number, frequency, and severity of adverse events using CTCAE version 4.03.
Time frame: Up to 3 years
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