Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition
Condition: Pancreas Cancer; Pancreatic Cancer; Cancer of the Pancreas
MeSH terms: Pancreatic Neoplasms
Intervention: Dapagliflozin; BIOSENSE meters
Intervention description: Dapagliflozin will be provided for this trial; -Being used in this trial to evaluate utility for assessing breath ketones
Intervention MeSH terms: Dapagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed metastatic or locally advanced 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 systemic therapy for pancreatic ductal adenocarcinoma in the metastatic or
             locally advanced 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

               -  Estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m^2

          -  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).

        Exclusion Criteria:

          -  History of total pancreatectomy

          -  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 exceptions 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.

          -  History of stroke or transient ischemic attack (in the last 5 years).

          -  HbA1c > 10% unless approved by endocrinologist

          -  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, 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.