Metformin for Lung Cancer Prevention in Overweight or Obese Individuals

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Saikrishna S Yendamuri

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

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

Disqualifiers: Diabetes, Liver disease, Alcohol abuse, others

No Placebo Group

Prior Safety Data

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

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.

What evidence supports the effectiveness of the drug metformin for preventing lung cancer in overweight or obese individuals?

Research suggests that metformin may lower the risk of lung cancer in diabetic patients, with some studies showing a significant reduction in cancer risk. However, the results are not entirely consistent, and factors like smoking can influence these findings. ^{1 2 3 4 5}

How is the drug metformin unique for lung cancer prevention?

Metformin is unique for lung cancer prevention because it is primarily a diabetes medication that may have protective effects against lung cancer, offering a novel approach compared to traditional cancer treatments. It is taken orally and has shown potential in reducing lung adenoma formation, making it a promising option for chemoprevention. ^{1 4 6 7 8}

Research Team

Saikrishna S Yendamuri

Principal Investigator

Roswell Park University

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Metformin (Anti-diabetic drug)

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.

Participant Groups

Group I: Cohort A (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 (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 Canada, Japan, China, Switzerland for the following indications:

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The effect of metformin and thiazolidinedione use on lung cancer in diabetics. [2022]

2. England 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. [2021]

3. Germany 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. [2021]

4. Thailand 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and meta-analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Fixed-Dose Combinations of Pioglitazone and Metformin for Lung Cancer Prevention. [2018]

7. United States 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. [2022]

8. United States 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. [2022]