Clinical trial NCT04542291: Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition
Official title: Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreas Cancer
Pancreatic Cancer
Cancer of the Pancreas
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2020-09-09
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Tolerability as Measured by Number of Participants With Related Adverse Events
timeFrame: From start of treatment through 30 days after treatment (estimated to be 3 months)
Secondary outcomes:
measure: Changes in Plasma Glucose
timeFrame: Screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, and End of Treatment (estimated to be 2 months)
measure: Changes in Ketones
timeFrame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 2 Day 15, and Cycle 2 Day 22
measure: Changes in HbA1c
timeFrame: Screening and Cycle 2 Day 15
measure: Changes in CA19-9
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, and End of Treatment, up to 8 weeks
measure: Changes in Total Fat Volume in Visceral Fat Area as Assessed by CT-based Body Composition
timeFrame: From pre-treatment and post-8 weeks of treatment
measure: Changes in Total Skeletal Muscle Volume in Visceral Fat Area as Assessed by CT-based Body Composition
timeFrame: From pre-treatment and post-8 weeks of treatment
measure: Changes in Total Muscle to Fat Ratio in Visceral Fat Area as Assessed by CT-based Body Composition
timeFrame: From pre-treatment and post-8 weeks of treatment
measure: Changes in CT-quantified Tumor Size
timeFrame: From pre-treatment and post-8 weeks of treatment
measure: Change in Tumor Necrosis
timeFrame: From pre-therapy to post-8 weeks of therapy
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Kian-Huat Lim, M.D.
role: PRINCIPAL_INVESTIGATOR
References: