Non Small Cell Lung CancerPhase 3METLUNGNCT05445791
Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations
A Phase 3 study testing Metformin Hydrochloride in people with Non Small Cell Lung Cancer, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Metformin Hydrochloride
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 312 participants
- Where
- 1 siteMexico
- Study dates
- 15 Jul 2021to 14 Jul 2027
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Measurable disease by RECIST 1.1.
- 18 years of age or older.
- Functional status 0-2 as assessed by Eastern Cooperative Oncology Group (ECOG) scale.
- Life expectancy of minimum12 weeks.
- Patients with non-small cell lung cancer and a documented EGFR sensitizing mutation.
Show all 17Show fewer
- Patients without previous EGFR-TKI treatment. Previous use of chemotherapy is allowed with a washout period of at least 6 months.
- Patients with asymptomatic brain metastases, or if symptoms are present treatment with radiotherapy (whole brain radiotherapy, stereotactic radiosurgery) or surgery must be administered.
- Neutrophil count ≥1.5 x 103/mm3, and platelet count >100 x (103/mm3).
- Serum bilirubin ≤1.5 the superior upper limit.
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2 superior upper limit (or ≤ 5 times the superior upper limit in patients with liver metastases).
- Serum creatinine ≤ 1.5 superior upper limit, or creatinine clearance ≥ 60ml/min.
- Full ability to complete all study procedures and follow up.
- Women with child-bearing potential must have a negative pregnancy test within 72 hours of treatment start.
- Patients with reproductive potential must use effective contraception.
- Signed informed consent for participation in the study.
- Availability of tumor tissue (pre-treatment biopsy) to determine LKB1 and AMPK status.
Who cannot join
- Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart disease, hepatic diseases, renal diseases).
- Patients previously treated with an EGFR-TKI.
- Patients diagnosed with any other neoplastic disease in the previous 5 years (except in situ cervical carcinoma or basocellular skin cancer, treated accordingly).
- 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.
- Pregnant or lactating women.
- Patients diagnosed with type 2 diabetes or a glycated hemoglobin ≥ 6.5%.
- Patients being currently treated with metformin.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional de Cancerologia
Mexico City, 14080
Oscar Arrieta, MD MSc, 015556280400 ext. 71100, ogarrieta@gmail.com
Diana Flores, 015556280400 ext. 71101, clinicacancerpulmonincan@gmail.com
About this study
Official title: Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone for Patients With Advanced Non-small Cell Lung Cancer and EGFR Mutations: Phase 3 Randomized Clinical Trial
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.
Read more
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.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- Metformin Hydrochloride, Placebo
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
Also called FICONAX
Metformin 500 mg twice daily until disease progression.
PlaceboOther
Placebo 500 mg twice daily until disease progression
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 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. Receives: Other: Placebo |
| Metformin | Experimental | 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. Receives: Drug: Metformin Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Time from treatment start until documented disease progression (according to RECIST criteria) or death by any cause.
Measured: 48 months
Secondary outcomes (2)
Overall survival
Time from treatment start until death by any cause.
Measured: 48 months
Overall Response Rate
The sum of complete and partial response as assessed by RECIST criteria version 1.1
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2022
- Study start15 Jul 2021
- Primary completion14 Jul 2026 (estimated)
- Study completion14 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 312 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cancerologia de Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Oscar Gerardo Arrieta Rodríguez, Instituto Nacional de Cancerologia de Mexico
- Investigators
- Oscar Gerardo Arrieta Rodríguez, Principal investigator, Instituto Nacional de Cancerologia de Mexico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05445791
- Sponsor's protocol ID
- (020/023/ICI) (CEI/1421/19)
- Acronym
- METLUNG
- Status last verified
- Apr 2026
- First submitted
- 30 Jun 2022
- Last updated
- 9 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Metformin Plus Tyrosine Kinase Inhibitors Compared With Tyrosine Kinase Inhibitors Alone for Patients With Advanced Non-small Cell Lung Cancer and EGFR Mutations: Phase 3 Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05445791
- Acronym / sponsor ID
- METLUNG / (020/023/ICI) (CEI/1421/19)
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 312 participants (estimated)
- Lead sponsor
- Instituto Nacional de Cancerologia de MexicoUniversity, hospital or other
- Study start
- 15 Jul 2021 (actual)
- Primary completion
- 14 Jul 2026 (estimated)
- Study completion
- 14 Jul 2027 (estimated)
- First posted
- 6 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPatients 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. |
| Metformin | Experimental | Drug: Metformin HydrochloridePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
- Measurable disease by RECIST 1.1.
- 18 years of age or older.
- Functional status 0-2 as assessed by Eastern Cooperative Oncology Group (ECOG) scale.
- Life expectancy of minimum12 weeks.
Key exclusion criteria (7 listed)
- Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart disease, hepatic diseases, renal diseases).
- Patients previously treated with an EGFR-TKI.
- Patients diagnosed with any other neoplastic disease in the previous 5 years (except in situ cervical carcinoma or basocellular skin cancer, treated accordingly).
- 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.
- Pregnant or lactating women.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin HydrochlorideAlso: FICONAXMetformin 500 mg twice daily until disease progression. | Drug | Metformin |
| PlaceboPlacebo 500 mg twice daily until disease progression | Other | Placebo |
Primary outcome
Progression-free survival
Time frame: 48 months
Time from treatment start until documented disease progression (according to RECIST criteria) or death by any cause.
2 secondary outcomes
Overall survival
Time frame: 48 months
Overall Response Rate
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Individual participant dataSharing planned: No
Related trials for Non Small Cell Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oscar Gerardo Arrieta Rodríguez principal investigator
Instituto Nacional de Cancerologia de Mexico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin Hydrochloride in people with Non Small Cell Lung Cancer, run by Instituto Nacional de Cancerologia de Mexico at 1 site in Mexico.
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 17 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Oscar Arrieta, M.Sc. (5556280400, oscararrietaincan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: 48 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2026.