Actively Recruiting
Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations
Led by Instituto Nacional de Cancerologia de Mexico · Updated on 2026-04-09
312
Participants Needed
1
Research Sites
312 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients with histologically confirmed non-small cell lung cancer (stage IIIB-IV) according to AJCC 8th edition
- Measurable disease by RECIST 1.1 criteria
- 18 years of age or older
- Functional status 0-2 on Eastern Cooperative Oncology Group (ECOG) scale
- Life expectancy of at least 12 weeks
- Documented EGFR sensitizing mutation
- No previous EGFR-TKI treatment; prior chemotherapy allowed after at least 6 months washout
- Patients with asymptomatic brain metastases or treated brain metastases via radiotherapy or surgery
- Neutrophil count ≥1.5 x 10^3/mm3 and platelet count >100 x 10^3/mm3
- Serum bilirubin ≤1.5 times upper limit of normal
- AST and/or ALT ≤2 times upper limit of normal (or ≤5 times if liver metastases present)
- Serum creatinine ≤1.5 times upper limit or creatinine clearance ≥60 ml/min
- Ability to complete all study procedures and follow up
- Women with child-bearing potential must have a negative pregnancy test within 72 hours before treatment
- Use of effective contraception for patients with reproductive potential
- Signed informed consent
- Availability of tumor tissue from pre-treatment biopsy to determine LKB1 and AMPK status
You will not qualify if you...
- Any unstable systemic disease including active infection, grade 4 hypertension, unstable angina, congestive heart failure, liver or kidney diseases
- Prior treatment with EGFR-TKI
- Other cancer diagnosis within past 5 years except treated in situ cervical carcinoma or basal cell skin cancer
- Inability to take oral medication, need for intravenous nutrition, recent surgery affecting nutrient absorption, or active peptic ulcer
- Pregnant or lactating women
- Diagnosis of type 2 diabetes or glycated hemoglobin ≥6.5%
- Current treatment with metformin
AI-Screening
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Trial Site Locations
Total: 1 location
1
Instituto Nacional de Cancerologia
Mexico City, Mexico, 14080
Actively Recruiting
Research Team
O
Oscar Arrieta, M.Sc.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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