Testing the Safety of Dapagliflozin Prior to Surgery for the Treatment of Patients With Stage IA Lung Adenocarcinoma

About

Brief Summary

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 Purpose

Treatment

Study Type

Interventional

Phase

Pilot/Feasibility

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

22 Years

Maximum Age

N/A

Inclusion Criteria:

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
Willing and able to receive a research CT-guided lung biopsy
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Leukocytes ≥ 3.0 K/mm^3
Absolute neutrophil count ≥ 1.5 K/mm^3
Platelets ≥ 100 K/mm^3
Total bilirubin ≤ 2 mg/dl
Aspartate aminotransferase (AST) ≤ 62 IU/L
Alanine aminotransferase (ALT) ≤ 70 IU/L
Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m^2
Diabetic status: diabetic subjects who are not currently receiving treatment will be included in the study. Diabetic subjects who are under treatment with insulin or oral anti-diabetic drugs will be enrolled under observation by endocrinologists on the team, to adjust the dose of the standard of care diabetic drugs to prevent hypoglycemia
Females of child-bearing potential must have a negative pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation. Females of childbearing potential must agree to avoid pregnancy during the study and omit to abstinence from heterosexual intercourse or agree to use two methods of birth control (one highly effective method and one additional effective method) at least 4 weeks before the start of protocol therapy
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion Criteria:

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
Currently receiving any other investigational agents
Currently receiving regularly scheduled systemic steroids in the form of prednisone or dexamethasone (more than 10 mg prednisone daily or equivalent). Topical steroid ointments or creams for occasional skin rash is allowed
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to dapagliflozin
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, ketoacidosis, severe kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m^2)
Subjects with HIV are eligible unless their cluster of differentiation 4 (CD4+) T-cell counts are < 350 cells/µL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective antiretroviral therapy (ART) according to Department of Health and Human Services (DHHS) treatment guidelines is recommended