This is a first-in-human, pilot study of the feasibility and safety of dapagliflozin (in
addition to standard of care treatment) for the treatment of patients with metastatic
pancreatic ductal adenocarcinoma. The primary hypothesis is that dapagliflozin is
well-tolerated and safe to use in this patient population. The investigators also hypothesize
that dapagliflozin will be efficacious as an adjunct to front-line chemotherapy assessed by
decreased tumor markers mediated by its pleiotropic metabolic effects.
- Histologically or cytologically confirmed pancreatic ductal adenocarcinoma, pancreatic
adenosquamous carcinoma or squamous cell carcinoma
- Patients with treated/stable brain metastases, defined as patients who have received
prior therapy for their brain metastases and whose CNS disease is radiographically
stable at study entry, are eligible.
- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- No prior therapy for pancreatic ductal adenocarcinoma in the metastatic setting.
- Planning to receive treatment with nab-paclitaxel and gemcitabine.
- At least 18 years of age.
- ECOG performance status ≤ 1
- Normal bone marrow and organ function as defined below:
- Leukocytes ≥ 3,000/mcL
- Absolute neutrophil count ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- Creatinine clearance > 30 mL/min by Cockcroft-Gault
- Because chemotherapeutic agents such as nab-paclitaxel and gemcitabine are known to be
teratogenic, women of childbearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control, abstinence) prior to study
entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she must inform her
treating physician immediately. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of the study,
and at least one month after completion of the study
- Agreement to adhere to Lifestyle Considerations throughout study duration
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- History of pancreatic resection/Whipple procedure.
- Current or previous treatment with SGLT2i or thiazolidinedione.
- Currently receiving regularly scheduled systemic steroids in the form of prednisone or
dexamethasone. Note that dexamethasone that can be prescribed for nausea on the day of
chemotherapy, but in subsequent days will be replaced by a nonsteroidal anti-emetic
for patients in this trial. Topical steroid ointments or creams for occasional skin
rash is allowed.
- A history of other malignancy with the exception of malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease as well as local treatment for skin squamous or basal cell
- History of stroke or transient ischemic attack (in the last 5 years).
- History of bladder cancer.
- HbA1c > 12%.
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to dapagliflozin, nab-paclitaxel, gemcitabine or other agents
used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, type 1 diabetes, peripheral arterial disease, ketoacidosis, severe kidney
disease (estimated glomerular filtration rate eGFR < 30 mL/min/1.73m2), symptomatic
hypotension, and chronic/frequent urinary tract infections or yeast infections.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
- Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or
they have a history of AIDS-defining opportunistic infection within the 12 months
prior to registration. Concurrent treatment with effective ART according to DHHS
treatment guidelines is recommended.