Combining Metformin with Tyrosine Kinase Inhibitors for Non-small Cell Lung Cancer Treatment

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

This study is testing if combining the diabetes drug Metformin with cancer medications can help people with advanced non-small cell lung cancer who have certain genetic changes.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 312 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Instituto Nacional de Cancerologia de Mexico (Academic / other)
• Drugs / interventions: chemotherapy, bevacizumab
• Locations: 1 site (Mexico City)
• Trial ID: NCT05445791 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy of combining Metformin Hydrochloride with tyrosine kinase inhibitors in patients diagnosed with non-small cell lung cancer (NSCLC) who have specific EGFR mutations. The study aims to enroll patients with advanced stages of NSCLC to evaluate the potential benefits of this combination therapy compared to a placebo. Participants must meet specific eligibility criteria, including having measurable disease and no prior treatment with EGFR-TKIs. The trial is designed to assess improvements in treatment outcomes for this challenging cancer type.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with stage IIIB-IV non-small cell lung cancer and documented EGFR sensitizing mutations.

Not a fit: Patients who have previously received EGFR-TKI treatment or those with symptomatic brain metastases not adequately treated may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with advanced non-small cell lung cancer harboring EGFR mutations.

How similar studies have performed: While the combination of Metformin with targeted therapies is a novel approach, previous studies have shown promise in using targeted therapies for NSCLC, indicating potential for success.

Eligibility criteria

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:

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.

Where this trial is running

Mexico City

• Instituto Nacional de Cancerologia — Mexico City, Mexico (Recruiting)

Study contacts

• Principal investigator: Oscar Gerardo Arrieta Rodríguez — Instituto Nacional de Cancerologia de Mexico
• Study coordinator: Oscar Arrieta, M.Sc.

Conditions Non Small Cell Lung Cancer