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

NCT03048500 | Unknown Phase 2 Results DMC FDA Drug

• 4 other identifiers: NU 16L04STU00204354P30CA060553NCI-2017-00060
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  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)

Secondary Outcomes (8)

• Depth of Response

  24 weeks from start of treatment

• Duration of Response

  Up to 3 years

• Persistence of Response

  Up to 3 years

• Disease Control Rate (DCR)

  24 weeks from start of treatment

• Progression-Free Survival (PFS)

  At 1 year than at 2 years

Study Arms (1)

Treatment (metformin hydrochloride, nivolumab)

EXPERIMENTAL

Patients receive metformin hydrochloride PO once QD on days -7 to -1 and 1-28. Patients also receive nivolumab 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.

Other: Laboratory Biomarker Analysis; Drug: Metformin Hydrochloride; Biological: Nivolumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (metformin hydrochloride, nivolumab)

Metformin Hydrochloride DRUG

Given PO

Also known as: Cidophage, Dimefor, Glifage, Glucoformin, Glucophage, Glucophage ER, Metformin HCl, Riomet, Siofor

Treatment (metformin hydrochloride, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (metformin hydrochloride, nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed, locally advanced or metastatic stage IV or non-resectable stage III non-small cell lung cancer (NSCLC)
• Patients may have received any number and type of prior treatment regimens for their NSCLC (aside from patients in arm A, who cannot have had PD-1/PD-L1 inhibitors)
• Arm A: patients must be treatment naive to single agent PD-1/PD-L1 inhibitors including but not limited to durvalumab, pembrolizumab, atezolizumab, nivolumab, and avelumab
• Arm B: patients' tumor must be either refractory to or progressed on one of the above agents
• Both cases are defined by initial progressive disease (PD) or PD after CR, PR, or SD using RECIST criteria, respectively
• Patients must have measurable disease according to the standard RECIST version 1.1
• NOTE: computed tomography (CT) scans or magnetic resonance imaging (MRI)s used to assess the measurable disease must have been completed with 28 days prior to the study drug initiation
• Patients need to have adequate kidney, bone marrow, and liver functions =\< 14 days of registration as specified below:
• Absolute neutrophil \>= 1,000/mcL; transfusion and/or growth factor are permitted within any timeframe
• Platelets \>= 50,000/mcl; transfusion and/or growth factor are permitted within any timeframe
• Total bilirubin =\< 1.5 times the institutional upper limit of normal (ULN) (or =\< 3 times ULN in case of liver metastasis or Gilbert syndrome)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SPGT\]) =\< 2.5 X institutional ULN (or =\< 5 times ULN in case of liver metastasis)
• Creatinine =\< 1.4 ng/mL for females; =\< 1.5 ng/mL for males; patients with creatinine =\< 2.0 ng/mL may still be eligible if in the opinion of the investigator, the benefits of treatment outweigh the risks
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

You may not qualify if:

• Both arms: patients should not have received metformin within 6 months prior to registration
• Arm B: patients who were on metformin while on PD-1/PD-L1 inhibitors are not eligible
• Patients should not have received prior immunotherapies (exception; arm B); they include but are not limited to interleukin-2 and other immune checkpoint antagonist targeting CTLA-4, LAG-3, TIM-3, KIR etc. and/or agonists targeting OX40, ICOS, CD137, etc
• NOTE: prior cancer vaccine treatments are permitted; for arm B, exposure to single agent PD-1/PD-L1 inhibitors are allowed \>= 14 days from registration
• Arm B: patients must not have had prior exposure to combination treatment with PD-1/PD-L1 inhibitors and another systemic treatment
• NOTE: radiation therapy and surgery do not count as combination treatment
• Patients who are intolerant to PD-1/PD-L1 inhibitors and/or metformin are excluded
• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded; these include but are not limited to patients with a history of:
• Immune related neurologic disease
• Multiple sclerosis
• Autoimmune (demyelinating) neuropathy
• Guillain-Barre syndrome
• Myasthenia gravis
• Systemic autoimmune disease such as systemic lupus erythematosus (SLE)
• Connective tissue diseases

Sponsors & Collaborators

• Northwestern University: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Metformin; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Young Chae, MD
• Organization: Northwestern University

young.chae@northwestern.edu

312-695-1301

Study Officials

• Young K. Chae, MD, MPH, MBA

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 9, 2017
• Study Start: July 12, 2017
• Primary Completion: September 19, 2019
• Study Completion: September 1, 2021
• Last Updated: October 14, 2020
• Results First Posted: October 14, 2020

Record last verified: 2020-09

Locations

US (2)