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.
PRIMARY OBJECTIVE: I. To assess safety and tolerability of administering 30 days of neoadjuvant dapagliflozin propanediol (dapagliflozin) before surgery in subjects with stage Ia lung adenocarcinoma. SECONDARY OBJECTIVE: I. To measure the effects of dapagliflozin on tumor cell proliferation in lung adenocarcinoma. EXPLORATORY OBJECTIVES: I. To measure the effects of neoadjuvant dapagliflozin on biological and metabolic parameters. II. To measure the effects of neoadjuvant dapagliflozin on biomarkers. OUTLINE: Patients receive dapagliflozin orally (PO) once daily (QD) for 30 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT)-guided biopsy on study and collection of blood and urine samples throughout the study. After completion of study treatment, patients are followed up between days 64 and 72.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Undergo collection of blood and urine samples
Undergo CT-guided biopsy
Given PO
Ancillary studies
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
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.
Time frame: Up to day 64-72
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.
Time frame: From biopsy to surgery up to day 64-72
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