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

Plain-language summary

This study evaluates whether adding Metformin (Metformin Hydrochloride) to tyrosine kinase inhibitor (EGFR-TKI) therapy, compared with placebo, benefits patients with non-small cell lung cancer that carries an EGFR gene mutation. Patients aged 18 and older with stage IIIB-IV disease, an EGFR sensitizing mutation, and no prior EGFR-TKI treatment may take part. The study is in Phase 3 and is still recruiting participants.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 3

Status

Recruiting

Sponsor

Instituto Nacional de Cancerologia de Mexico

Intervention

Metformin Hydrochloride, Placebo

Start date

7/15/2021

Estimated completion

7/14/2027

Countries

Mexico

Related genes

Locations

• Mexico City, Mexico

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.