The Addition of Metformin to Definitive Radiotherapy in Patients With Stage III NSCLC

Inclusion Criteria:

* Provision of signed and dated informed consent form.
* Stated willingness to comply with all study procedures and availability for the duration of the study.
* Ability to take oral medication and willing to adhere to the RADFORMIN-regimen.
* Male or female, ≥ 18 years of age.
* Histological or cytological proven stage III NSCLC after adequate staging with at least 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT, contrast enhanced CT-thorax and contrast-enhanced CT/MRI brain. (According to 8th edition of TNM classification (= tumor, node, metastasis))
* Absence of diabetes, (diabetes is defined as fasting plasma glucose \>126 mg/dL or random plasma glucose \>200 mg/dL).
* Eastern Cooperative Oncology Group (ECOG) performance score (= World Health Organization (WHO) score) of 0-1.
* Adequate hematologic, hepatic and renal function as clinically acceptable in the opinion of the Primary Investigator.
* Adequate pulmonary function in order to be administered definitive radiotherapy. With Forced Expiratory Volume (FEV) \> 1.2 litres per second or more than 50% of predicted, and diffusion capacity of lung for carbon monoxide (DLCO) \> 40% predicted. (Values without administration of medical bronchodilation. In case of Tiffeneau \< 70% bronchodilation will be administered)
* Having received at least 2 cycles of platinum-based chemotherapy. This according to institutional standards and without progression (on a restaging CT-scan within 3 weeks after day 1 of the last given cycle, according to RECIST criteria).

Exclusion Criteria:

* Current use of metformin, insulin or other oral antidiabetic drugs (thiazolidinediones, sulfonylureas, mitiglinides, alpha-glucosidase inhibitors, incretin mimetics, dipeptidyl peptidase-4 inhibitors, amylin analogues, sodium-glucose-cotransporter-2 (SGLT-2)-inhibitors) for any reason.
* Evidence for metastatic disease.
* Conditions associated with increased risk of metformin-associated lactic acidosis: New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, known kidney injury or disease, alcoholic liver disease or habitual intake of 3 or more alcoholic beverages per day.
* Known pregnancy or lactating female patients.
* Known allergic reactions to components of metformin.
* Prior invasive malignancy within the past year (in remission, without evidence for current active disease and without maintenance therapy). Except non-melanomatous skin cancer, non-invasive carcinoma in-situ of the breast, oral cavity or cervix.
* Known acquired immune deficiency syndrome.