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RecruitingNCT05445791METLUNGUpdated Apr 9, 2026

Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations

A Phase 3 interventional study of Metformin Hydrochloride and Placebo in Non Small Cell Lung Cancer, sponsored by Instituto Nacional de Cancerologia de Mexico. Recruiting at 1 site in Mexico. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-09.

Sponsored by Instituto Nacional de Cancerologia de Mexico · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
312
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Lung cancer is the most common neoplastic disease globally, with over 2 million new cases annually, accounting for 11.6% of all cancer diagnoses. It remains the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) makes up 80-85% of lung cancer cases, with most patients diagnosed at an advanced stage. Five-year survival rates are low, ranging from 8-18% worldwide.

Advances in molecular biology have led to the identification of therapeutic targets in NSCLC. One of the most studied is the epidermal growth factor receptor (EGFR), a key regulator of tumor cell functions and a focus of targeted therapy development. EGFR mutations occur in about 15% of NSCLC cases globally but reach up to 34% in Mexico. Patients with these mutations are treated with tyrosine kinase inhibitors (TKIs), which improve response rates and progression-free survival (PFS) over chemotherapy. However, resistance to TKIs typically develops, prompting the need for strategies to overcome this challenge and extend PFS.

Up to 30% of NSCLC patients have somatic mutations in the liver kinase B1 (LKB1) gene, a tumor suppressor that inhibits mTOR. In one study, 24 patients with LKB1 expression treated with metformin plus TKIs showed significantly improved overall survival. LKB1 activates AMP-activated protein kinase (AMPK), which regulates cell cycle and survival in NSCLC. Loss of LKB1 reduces AMPK activation and increases tumor necrosis following bevacizumab treatment. A study of 99 NSCLC samples linked high AMPK expression to poorer survival, though its role in metformin response is unclear.

Metformin, a biguanide used for type 2 diabetes, has shown anticancer properties. Studies suggest metformin reduces cancer incidence and mortality. In vitro, it induces G0/G1 cell cycle arrest and counters TKI resistance due to epithelial-mesenchymal transition (EMT). Retrospective studies support its benefit in NSCLC, and prospective trials of metformin plus TKIs have yielded mixed results.

This phase 3 randomized study aims to evaluate PFS in NSCLC patients with EGFR mutations treated with TKIs plus placebo versus TKIs plus metformin.

02

Conditions studied

  • Non Small Cell Lung Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patients with a histologically confirmed diagnosis of non-small cell lung cancer (stage IIIB-IV) according to the American Joint Committee on Cancer (AJCC) eight edition.
  2. Measurable disease by RECIST 1.1.
  3. 18 years of age or older.
  4. Functional status 0-2 as assessed by Eastern Cooperative Oncology Group (ECOG) scale.
  5. Life expectancy of minimum12 weeks.
  6. Patients with non-small cell lung cancer and a documented EGFR sensitizing mutation.
  7. Patients without previous EGFR-TKI treatment. Previous use of chemotherapy is allowed with a washout period of at least 6 months.
  8. Patients with asymptomatic brain metastases, or if symptoms are present treatment with radiotherapy (whole brain radiotherapy, stereotactic radiosurgery) or surgery must be administered.
  9. Neutrophil count ≥1.5 x 103/mm3, and platelet count >100 x (103/mm3).
  10. Serum bilirubin ≤1.5 the superior upper limit.
  11. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2 superior upper limit (or ≤ 5 times the superior upper limit in patients with liver metastases).
  12. Serum creatinine ≤ 1.5 superior upper limit, or creatinine clearance ≥ 60ml/min.
  13. Full ability to complete all study procedures and follow up.
  14. Women with child-bearing potential must have a negative pregnancy test within 72 hours of treatment start.
  15. Patients with reproductive potential must use effective contraception.
  16. Signed informed consent for participation in the study.
  17. Availability of tumor tissue (pre-treatment biopsy) to determine LKB1 and AMPK status.

Exclusion criteria

Exclusion Criteria:

  1. Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart disease, hepatic diseases, renal diseases).
  2. Patients previously treated with an EGFR-TKI.
  3. Patients diagnosed with any other neoplastic disease in the previous 5 years (except in situ cervical carcinoma or basocellular skin cancer, treated accordingly).
  4. Patients unable to receive oral medication, who require IV nourishment, or who underwent surgical procedures with affect nutrient absorption, or with an active peptic ulcer.
  5. Pregnant or lactating women.
  6. Patients diagnosed with type 2 diabetes or a glycated hemoglobin ≥ 6.5%.
  7. Patients being currently treated with metformin.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
312 participants (estimated)

Study arms

  • Placebo comparator
    Placebo

    Patients randomized to this study arm will be treated with tyrosine kinase inhibitors (Gefitinib 250 mg/day; afatinib 30-40 mg/day; erlotinib 150 mg/day) plus placebo 500 mg twice daily until disease progression.

    Other: Placebo

  • Experimental
    Metformin

    Patients randomized to this study arm will be treated with tyrosine kinase inhibitors (Gefitinib 250 mg/day; afatinib 30-40 mg/day; erlotinib 150 mg/day) plus metformin 500 mg twice daily until disease progression.

    Drug: Metformin Hydrochloride

Interventions

  • DrugMetformin Hydrochloride

    Metformin 500 mg twice daily until disease progression.

    Also known as: FICONAX

  • OtherPlacebo

    Placebo 500 mg twice daily until disease progression

05

What researchers measure

Primary outcomes

  1. Progression-free survival

    Time from treatment start until documented disease progression (according to RECIST criteria) or death by any cause.

    Time frame: 48 months

Secondary outcomes

  1. Overall survival

    Time from treatment start until death by any cause.

    Time frame: 48 months

  2. Overall Response Rate

    The sum of complete and partial response as assessed by RECIST criteria version 1.1

    Time frame: 3 months

06

Study locations

1 of 1 sites recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT05445791
Lead sponsor
Instituto Nacional de Cancerologia de Mexico
Responsible party
Oscar Gerardo Arrieta Rodríguez (Coordinator of the Thoracic Oncology Unit, Instituto Nacional de Cancerologia de Mexico) — Principal investigator
First posted
Jul 6, 2022
Start date
Jul 15, 2021
Primary completion
Jul 14, 2026 (estimated)
Completion
Jul 14, 2027 (estimated)
Last update
Apr 9, 2026

Study contacts

Oscar Arrieta, M.Sc.
Contact
oscararrietaincan@gmail.com
5556280400
Oscar Gerardo Arrieta Rodríguez
principal investigator · Instituto Nacional de Cancerologia de Mexico

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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