NCT04931017

Metformin for Chemoprevention of Lung Cancer in Overweight or Obese Individuals at High Risk for Lung Cancer

Metformin for Chemoprevention of Lung Cancer in High-Risk Overweight or Obese Individuals

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: Northwestern University · Academic / Other
• Sex: All
• Age: 30 Years
• Healthy volunteers: Accepted

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.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the effect of metformin treatment on the expression of programmed cell death protein 1 (PD-1) on airway regulatory T cells (Tregs) in overweight and obese individuals at high risk for lung cancer. SECONDARY OBJECTIVES: I. Estimated PD-1 expression of pulmonary Tregs change in Cohort B during the wait period (26 weeks with no treatment). II. To examine the impact of metformin on circulating immune cell subsets of blood. III. To evaluate the effect of metformin treatment on the expression of PD-1 on airway regulatory T cells (Tregs) in overweight and obese current smokers at high risk for lung cancer EXPLORATORY OBJECTIVES: I. To examine the impact of metformin on cancer-related transcriptome features of airway lesions. II. To examine the impact of metformin on immune profile of pulmonary parenchyma represented by bronchoalveolar lavage (BAL). III To examine the impact of metformin on histologic progression of abnormal airway lesions. IV. To examine the impact of metformin on serum adipokines and inflammatory cytokines. OUTLINE: Participants are randomized to 1 of 2 cohorts. COHORT A: Former Smokers - Participants receive metformin extended release (ER) orally (PO) once daily (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 - Participants 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. COHORT C: Current Smokers - Participants receive metformin extended release (ER) orally (PO) once daily (QD) for 26 weeks in the absence of unacceptable toxicity. Participants undergo bronchoscopy biopsy and blood sample collection at screening, and week 13. After completion of study treatment, participants are followed up at weeks 30-32 (Cohorts A and C) and weeks 56-58 (Cohort B).

Conditions

• Lung Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bronchoscopy	Undergo bronchoscopy
DRUG	Extended Release Metformin Hydrochloride	Given PO
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2022-09-09
• Primary completion: 2026-12-31
• Completion: 2027-06-30
• First posted: 2021-06-18
• Last updated: 2025-10-07

Locations

4 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study