Nivolumab and Metformin Hydrochloride in Treating Patients With Stage III-IV Non-small Cell Lung Cancer That Cannot Be Removed by Surgery

Stage IV Non-Small Cell Lung Cancer Clinical Trial

Official title: Parallel Proof of Concept Phase 2 Study of Nivolumab and Metformin Combination Treatment in Advanced Non-small Cell Lung Cancer With and Without Prior Treatment With PD-1/PD-L1 Inhibitors

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Non-Small Cell Lung Carcinoma
• Stage III Non-Small Cell Lung Cancer
• Stage IIIA Non-Small Cell Lung Cancer
• Stage IIIB Non-Small Cell Lung Cancer
• Stage IV Non-Small Cell Lung Cancer

• NCT number: NCT03048500
• Study type: Interventional
• Source: Northwestern University
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 12, 2017
• Completion date: September 2021