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Lung CarcinomaPhase 2NCT04931017

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

A Phase 2 study testing Biopsy, Biospecimen Collection and Bronchoscopy in people with Lung Carcinoma, run by Northwestern University at 4 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 30 years and olderHealthy volunteers can take part
Conditions the study is for
Lung Carcinoma
What is being tested?
Biopsy, Biospecimen Collection and Bronchoscopy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
4 sitesin 2 countries
Study dates
9 Sep 2022to 30 Jun 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 30 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United States2 sites

  • Rocky Mountain Regional VA Medical Center

    Aurora, Colorado, 80045

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

Canada2 sites

  • BC Cancer Research Centre

    Vancouver, British Columbia, V5Z 1L3

  • University of British Columbia Hospital

    Vancouver, British Columbia, V6T 2B5

Other trials in Canada

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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
Being tested
Biopsy, Biospecimen Collection, Bronchoscopy, Extended Release Metformin Hydrochloride, Questionnaire Administration
Medical subject headings
Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • BronchoscopyProcedure or surgery

    Undergo bronchoscopy

  • Extended Release Metformin HydrochlorideDrug

    Also called ER Metformin Hydrochloride, Extended-release Metformin Hydrochloride, Glucophage XR, Glumetza

    Given PO

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04931017
Study groupRoleWhat they receive
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.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bronchoscopy; Drug: Extended Release Metformin Hydrochloride; Other: Questionnaire Administration
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.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bronchoscopy; Drug: Extended Release Metformin Hydrochloride; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Pre- to post-treatment

Secondary outcomes (2)

  1. Estimated PD-1 expression of pulmonary Tregs change in cohort B during the wait period (6 months with no treatment)

    This is the estimate of change in MFI following the 6-month wait period among n = 20 subjects randomized to the wait-list arm. This will confirm the stability of the PD-1 expression of pulmonary Tregs over time.

    Measured: Randomization to week 26

  2. Circulating immune cells

    Circulating immune cell composition between blood samples collected pre- and post-metformin ER treatment to assess the effect of metformin ER on circulating immune cells and to identify potential biomarkers of metformin ER response.

    Measured: Pre- to post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2021
  2. Study start9 Sep 2022
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion30 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Crossover
Model description
This is a partial crossover model whereby the no-treatment subjects will receive the drug after being controls.
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04931017
Sponsor's protocol ID
NCI-2021-06112
Other IDs
NCI-2021-06112, NCI20-04-01, NWU20-04-01, P30CA060553, UG1CA242643
Status last verified
Oct 2025
First submitted
17 Jun 2021
Last updated
7 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Biospecimen Collection and Bronchoscopy in people with Lung Carcinoma, run by Northwestern University at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PD-1 expression of pulmonary regulatory T cells (Tregs) before and after metformin extended release (ER) treatment (time frame: Pre- to post-treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04931017.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2025.

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