This early phase I trial tests the safety and side effects of dapagliflozin given prior to surgery in patients with stage IA lung adenocarcinoma. Dapagliflozin is approved by the Food and Drug Administration (FDA) for the treatment of diabetes and heart failure. It is an SGLT2 inhibitor. Stage I lung adenocarcinomas express significantly higher levels of the SGLT2 protein than other stages, and research suggests that SGLT2 inhibition improves lung cancer outcomes in patients with diabetes. In this study, dapagliflozin is being used off-label, which means it is being used for a condition that it was not originally approved for by the FDA. The investigational study drug is a neoadjuvant treatment, meaning the drug is given before surgery to try and help make the surgery more effective.
Must be able to provide written informed consent
Male or female ≥ 22 years of age at visit 1
Histologically confirmed stage Ia lung adenocarcinoma, with availability of biopsy tissue for Ki-67 determination
Planning to undergo surgery for lung adenocarcinoma
Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Women of child-bearing age will receive a urine pregnancy test to confirm eligibility
Unsuitable candidate for the study, based on the opinion of the Investigator (e.g., cognitive impairment), such that participation might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or complete the study
Current or previous treatment with SGLT2 inhibitors
History of other malignancies with exception of malignancies for which all treatment was completed at least 2 years before registration with no evidence of disease and locally treated skin squamous or basal cell carcinoma
Single group
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood and urine samples
Computed Tomography Assisted Biopsy
Procedure/SurgeryUndergo CT-guided biopsy
Dapagliflozin Propanediol
DrugGiven PO
Questionnaire Administration
Other interventionAncillary studies
Incidence of adverse events
Will be measured by frequency and severity of toxicities related to dapagliflozin per Common Terminology Criteria for Adverse Events version 6.0. Data will be summarized. Adverse events, severe adverse events, and adverse drug reactions will be coded by body system and Medical Dictionary for Regulatory Activities classification term. Adverse events will be tabulated and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug.
Tumor cell proliferation change
Tumor cell proliferation change will be measured by percentage of Ki-67-positive cells at 3 separate timepoints: 1. pre-treatment archival tissue of standard of care diagnostic lung biopsy samples; 2. pre-treatment research computed tomography-guided lung biopsy; 3. post-treatment archival tissue from the standard of care lung tissue sample from the surgical resection. Will utilize mixed effect negative binomial regression models to compare the Ki-67 in pre- versus post-investigational study drug treatment lung biopsy samples. The outcome in these models will be the number of Ki-67 positive cells in the lung biopsy. The primary inference for the efficacy of the treatment will be the time effect in the model which will test whether the rate of Ki-67 positivity changes is due to the treatment.
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