Using metformin to prevent lung cancer in overweight or obese individuals at high risk
Metformin for Chemoprevention of Lung Cancer in High-Risk Overweight or Obese Individuals
This study is testing if the diabetes drug metformin can help prevent lung cancer in overweight or obese former smokers who are at high risk.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 75 (estimated) |
| Ages | 30 Years and up |
| Sex | All |
| Sponsor | Northwestern University Academic / other |
| Locations | 4 sites (Aurora, Colorado and 3 other locations) |
| Trial ID | NCT04931017 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the effects of metformin extended release on reducing the risk of lung cancer in overweight or obese individuals who are former smokers with a significant smoking history. The study evaluates how metformin influences immune responses, particularly focusing on the expression of programmed cell death protein 1 (PD-1) on regulatory T cells in the airways. Participants are randomized into two cohorts, with one receiving metformin for 26 weeks while the other serves as a control before crossing over to treatment. The trial also examines various immune and cancer-related biomarkers to assess the drug's potential as a preventative measure against lung cancer.
Who should consider this trial
Good fit: Ideal candidates include former smokers aged over 30 who are overweight and have a significant smoking history.
Not a fit: Patients who are not former smokers or those with a BMI below 25 may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly lower the incidence of lung cancer in high-risk populations, improving patient outcomes.
How similar studies have performed: Other studies have shown promising results with metformin in cancer treatment, suggesting potential for success in this preventative approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 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
* Estimated glomerular filtration rate (eGFR) \> 45 ml/min/1.73 m\^2 (eGFR will be calculated using the equation Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine)
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured
* Patients on chronic suppressive antiviral therapy for herpes simplex virus (HSV) are eligible
* The effects of metformin ER on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
* 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
* Participants with prior stage 1 non-small cell lung cancer (NSCLC) diagnosis are allowed to participate, as long as there has been 12 months since the completion of cancer treatment prior to enrollment with no evidence of recurrence or second primary cancer
Where this trial is running
Aurora, Colorado and 3 other locations
- Rocky Mountain Regional VA Medical Center — Aurora, Colorado, United States (Recruiting)
- Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)
- BC Cancer Research Centre — Vancouver, British Columbia, Canada (Recruiting)
- University of British Columbia Hospital — Vancouver, British Columbia, Canada (Not_yet_recruiting)
Study contacts
- Principal investigator: Saikrishna S Yendamuri — Roswell Park University
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.