Metformin for Lung Cancer Prevention in Overweight or Obese Individuals

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Immunosuppressants, Steroids, GLP-1 agonists, others

Disqualifiers: Diabetes, Liver disease, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin can help prevent lung cancer in overweight or obese individuals with a history of smoking. Metformin, commonly used for type II diabetes, is known for its safety and minimal side effects. Researchers hope it might also enhance the immune system's ability to fight cancer. The trial includes two groups of former smokers: one taking metformin and another waiting before starting the drug. Ideal candidates are former smokers with a 20+ pack-year history, who quit smoking at least a year ago and are currently overweight. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using immunosuppressive medication or systemic steroids. If you are on these medications, you would need to stop them to join the trial.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research has shown that metformin, a common medication for type II diabetes, is generally safe and well-tolerated, with few side effects. It has been used for many years. Studies suggest that metformin not only helps control diabetes but may also help prevent cancer. For instance, people taking metformin have shown a lower risk of developing certain cancers, such as lung cancer.

Additionally, metformin might boost the body's ability to fight cancer by strengthening the immune system's response to cancer cells. Large-scale studies indicate that metformin could reduce the risk of cancer more effectively than other diabetes medications.

In summary, metformin has a long track record of safe use and shows potential in cancer prevention, making it a promising option for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about metformin for lung cancer prevention because it offers a novel approach compared to traditional treatments like surgery, radiation, and chemotherapy. Unlike these standard options, metformin, a common diabetes medication, may reduce cancer risk by targeting metabolic pathways linked to obesity and smoking-related damage. This drug is administered orally and is being explored for its potential to prevent cancer rather than treat it, which could revolutionize how we approach lung cancer risk in overweight or obese individuals.

What evidence suggests that metformin might be an effective treatment for preventing lung cancer?

Research has shown that metformin might lower the risk of developing lung cancer, particularly in individuals who are overweight or obese. Studies found that people taking metformin had a 22% lower chance of developing lung cancer compared to those not taking it. Metformin is also associated with better survival rates in lung cancer patients and may enhance the immune system's ability to fight tumors. In this trial, participants in Cohort A will receive metformin ER, while those in Cohort B will initially have a waiting period before crossing over to receive metformin ER. These findings suggest that metformin could be a promising option for preventing lung cancer in high-risk groups. ^{6 7 8 9 10}

Who Is on the Research Team?

Saikrishna S Yendamuri

Principal Investigator

Roswell Park University

Are You a Good Fit for This Trial?

This trial is for overweight or obese adults over 30 years old at high risk for lung cancer, with a specific lung cancer risk score and no history of diabetes. They must have quit smoking for at least a year, have normal organ function tests, and agree to use contraception. People with previous metformin use, certain medical conditions like severe liver disease or heart failure, or those on immunosuppressive drugs can't join.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1,000/microliter

Platelets >= 100,000/microliter

Leukocytes >= 3,000/microliter

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin ER

You are currently taking medication that is not yet approved by the FDA for your condition.

I am not taking any immunosuppressive medication, including systemic steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment (Cohort A)

Participants receive metformin extended release (ER) orally once daily for 26 weeks. Bronchoscopy biopsy and blood sample collection occur at screening and week 13.

26 weeks

2 visits (in-person)

Waiting Period (Cohort B)

Participants receive no intervention for 26 weeks before crossing over to Cohort A.

26 weeks

2 visits (in-person)

Treatment (Cohort B)

After the waiting period, participants cross over to receive metformin ER for 13 weeks. Bronchoscopy biopsy and blood sample collection occur at week 26 and 13 weeks after crossover.

13 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2-4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview

The study is testing if extended release Metformin can prevent lung cancer in high-risk individuals by possibly reprogramming the immune system to reduce harmful cells linked to tumors. Participants will undergo bronchoscopy, biopsies and give biospecimens while taking Metformin and answering questionnaires about their health.

How Is the Trial Designed?

Group I: Cohort A - Former Smokers (metformin ER) Experimental Treatment 5 Interventions

Participants 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.

Group II: Cohort B - Former Smokers (metformin ER with waiting period) Active Control 5 Interventions

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.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study using A/J mice, the combination of metformin and pioglitazone significantly reduced lung adenoma formation after 15 weeks, suggesting potential for lung cancer chemoprevention.

Metformin alone was effective at doses between 500 to 1,000 mg/kg/d, while pioglitazone was effective only at early-stage interventions, indicating that metformin may be the more potent chemopreventive agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fixed-Dose Combinations of Pioglitazone and Metformin for Lung Cancer Prevention. Seabloom, DE., Galbraith, AR., Haynes, AM., et al.[2018]

Metformin treatment is associated with a reduced risk of developing lung cancer (hazard ratio 0.78) and improved survival rates in lung cancer patients (hazard ratio 0.65), based on a meta-analysis of 18 studies involving both risk and survival outcomes.

The protective effects of metformin were particularly significant among Asian patients for lung cancer risk (hazard ratio 0.66) and were observed in both Asian and non-Asian patients for survival, indicating its potential as a beneficial treatment in lung cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of metformin on lung cancer risk and survival in patients with type 2 diabetes mellitus: A meta-analysis. Xiao, K., Liu, F., Liu, J., et al.[2021]

In a phase 2 clinical trial involving 170 patients with unresectable stage III non-small cell lung cancer (NSCLC), the addition of metformin to chemoradiation did not improve one-year progression-free survival compared to chemoradiation alone, with rates of 51.3% in the metformin group versus 60.4% in the control group.

Both treatment groups had similar overall survival rates (around 80%) and experienced no significant differences in adverse events, indicating that while metformin was well tolerated, it did not enhance the effectiveness of standard treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial. Skinner, H., Hu, C., Tsakiridis, T., et al.[2022]

Metformin use in diabetic patients is associated with a significantly lower risk of lung cancer (pooled relative risk = 0.71) and respiratory cancers (pooled relative risk = 0.85), based on a review of studies conducted between 2009 and 2013.

However, the association may be influenced by smoking status, as studies that adjusted for smoking showed a weaker relationship, indicating that caution is needed in interpreting these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and meta-analysis. Zhang, ZJ., Bi, Y., Li, S., et al.[2022]

In a study of 93,939 diabetic patients, those using metformin and/or thiazolidinediones (TZDs) had a significantly lower likelihood of developing lung cancer compared to those who did not use these medications.

Among diabetic patients who did develop lung cancer, those on metformin alone exhibited a more aggressive cancer phenotype, presenting with more metastatic disease and shorter survival rates after diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of metformin and thiazolidinedione use on lung cancer in diabetics. Mazzone, PJ., Rai, H., Beukemann, M., et al.[2022]

A systematic review and meta-analysis of 15 studies involving patients with diabetes found no significant association between the use of anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones, or insulin) and the risk of developing lung cancer.

The analysis revealed considerable heterogeneity among the studies, indicating that more well-designed, prospective research is needed to clarify any potential links between anti-diabetic medications and lung cancer risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-diabetic medications do not influence risk of lung cancer in patients with diabetes mellitus: a systematic review and meta-analysis. Nie, SP., Chen, H., Zhuang, MQ., et al.[2022]

Observational studies suggest that metformin use is associated with improved overall survival in lung cancer patients, particularly when a time-dependent analysis is applied, highlighting the importance of study design in assessing treatment effects.

In contrast, randomized clinical trials did not show any benefit of metformin on overall or progression-free survival, indicating a need for more rigorous and well-designed trials to clarify the relationship between metformin and lung cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of metformin on lung cancer survival: the first systematic review and meta-analysis of observational studies and randomized clinical trials. Brancher, S., Ribeiro, AE., Toporcov, TN., et al.[2021]

In a study of 215 patients with early-stage non-small cell lung cancer, diabetic patients taking metformin showed significantly improved progression-free survival compared to those not taking metformin and nondiabetic individuals, suggesting a potential benefit of metformin in cancer treatment.

Despite the improved progression-free survival in metformin users, there was no observed difference in overall survival, indicating that while metformin may help delay cancer progression, it does not necessarily extend life in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non-small cell lung cancer. Medairos, RA., Clark, J., Holoubek, S., et al.[2022]

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