Metformin for Chemoprevention of Lung Cancer in Overweight or Obese Individuals at High Risk for Lung Cancer
5 other identifiers
interventional
50
2 countries
4
Brief Summary
This phase II trial determines the effect of metformin extended release on the risk for developing lung cancer in overweight/obese patients that are at high-risk for developing lung cancer. Metformin is widely used to treat type II diabetes and has a long history of safety and minimal side effects. At similar dosage, the drug may have potential anti-cancer activity. Metformin use has been associated with improved survival in patients with non-small cell lung carcinoma, a specific type of lung cancer, and it has also been shown to enhance immune mobilization against tumors. This trial aims to see whether metformin extended release as a preventative treatment may lower the chance of developing lung cancer, and whether it may help patients' immune system learn ("reprogram") to lower a certain type of immune cell (called regulatory T cells) that are linked to tumor development.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Sep 2022
Longer than P75 for phase_2
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2021
CompletedFirst Posted
Study publicly available on registry
June 18, 2021
CompletedStudy Start
First participant enrolled
September 9, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2027
October 7, 2025
October 1, 2025
4.3 years
June 17, 2021
October 1, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
PD-1 expression of pulmonary regulatory T cells (Tregs) before and after metformin extended release (ER) treatment
Change from pre- to post-metformin extended release (ER) treatment in cell surface PD-1 expression levels of pulmonary (BAL) Tregs, measured as mean fluorescent intensity (MFI). Changes in MFI due to metformin ER treatment among all n = 40 subjects will be used for the primary analysis.
Pre- to post-treatment
Secondary Outcomes (2)
Estimated PD-1 expression of pulmonary Tregs change in cohort B during the wait period (6 months with no treatment)
Randomization to week 26
Circulating immune cells
Pre- to post-treatment
Other Outcomes (4)
Airway gene expression
Up to study completion
Examination of the immune profile of pulmonary parenchyma represented by bronchoalveolar lavage
Pre- to post-treatment
Histologic progression
Up to study completion
- +1 more other outcomes
Study Arms (2)
Cohort A - Former Smokers (metformin ER)
EXPERIMENTALParticipants receive metformin ER PO QD for 26 weeks in the absence of unacceptable toxicity. Participants undergo bronchoscopy biopsy and blood sample collection at screening, and week 13.
Cohort B - Former Smokers (metformin ER with waiting period)
ACTIVE COMPARATORParticipants receive no intervention for 26 weeks, then cross-over to Cohort A. Participants undergo bronchoscopy biopsy and blood sample collection at screening, at week 26, and at 13 weeks after cross-over to Cohort A.
Interventions
Undergo biopsy
Undergo blood sample collection
Undergo bronchoscopy
Given PO
Ancillary studies
Eligibility Criteria
You may qualify if:
- Former smokers (male and female) with a \>= 20 pack year smoking history
- Quit smoking \>= 12 months prior to enrollment
- Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCOm2012) Lung Cancer Risk Prediction Score \> 1.34%
- Overweight
- Body mass index (BMI) \> 25 and
- Waist circumference
- Female \> 88 cm (35")
- Male \> 102 cm (40")
- Age greater than 30 years. Participants younger than 30 years are unlikely to accrue enough smoking exposure followed by enough time after quitting (\>12 months) to qualify
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
- Leukocytes \>= 3,000/microliter
- Absolute neutrophil count (ANC) \>= 1,000/microliter
- Platelets \>= 100,000/microliter
- Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x IULN
- +5 more criteria
You may not qualify if:
- Current or previous diagnosis of diabetes mellitus (type I or type II diabetes)
- Use of metformin within the past 2 years
- Use of GLP-1 agonists within 6 weeks prior to enrollment
- Glycosylated hemoglobin A1C (HbA1c) \> 8%
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin ER
- Participants currently using immunosuppressive medication, including systemic steroids (not inhalational) and episodic use of inhaled steroids are excluded from this trial due to the potential impact of these treatments on the primary trial endpoint
- Participants receiving any other investigational agents
- History of chronic alcohol use or abuse defined by any one of the following:
- Average consumption of 3 or more alcohol containing beverages daily in the past 12 months
- Consumption of 7 or more alcoholic beverages within a 24 hour period in the past 12 months
- Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension
- History of or current condition predisposing to increased risk for lactic acidosis such as: severe congestive heart failure (New York Heart Association \[NYHA\] class III or IV), metabolic acidosis, severe liver disease, or renal failure
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would or limit compliance with study requirements
- Pregnant women are excluded from this study. Metformin ER is a class B agent that was not teratogenic in rats and rabbits at doses representing 3 and 6 times the maximum recommended human daily dose of 2000 mg; however, animal reproduction studies are not always predictive of human response. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin ER, breastfeeding should be discontinued if the mother is treated with metformin ER
- Biopsy with invasive carcinoma of the lung or carcinoma in situ
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Northwestern Universitylead
- National Cancer Institute (NCI)collaborator
Study Sites (4)
Rocky Mountain Regional VA Medical Center
Aurora, Colorado, 80045, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
BC Cancer Research Centre
Vancouver, British Columbia, V5Z 1L3, Canada
University of British Columbia Hospital
Vancouver, British Columbia, V6T 2B5, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Saikrishna S Yendamuri
Roswell Park University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 17, 2021
First Posted
June 18, 2021
Study Start
September 9, 2022
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
June 30, 2027
Last Updated
October 7, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.