Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dapagliflozin Dapagliflozin is an oral drug which will be administered on an outpatient basis. Dosing will start at 5 mg daily and will increase to 10 mg daily after 2 weeks (after consulation with a study endrocrinologist) if the patient is tolerating the 5 mg dose. Dapagliflozin will be given for a total of 8 weeks (2 weeks at 5 mg and 6 weeks at 10 mg) Treatment with dapagliflozin will be initiated on Cycle 1 Day 1 of standard of care chemotherapy. Participants will use the BIOSENSE meter once daily |
Drug: Dapagliflozin
Dapagliflozin will be provided for this trial
Other Names:
Device: BIOSENSE meters
-Being used in this trial to evaluate utility for assessing breath ketones
|
Outcome Measures
Primary Outcome Measures
- Tolerability as measured by incidence of adverse events measured by CTCAE v. 5.0 [From start of treatment through 30 days after treatment (estimated to be 3 months)]
-Adverse events will be graded with CTCAE v. 5.0.
Secondary Outcome Measures
- Changes in plasma glucose [From start of treatment until end of treatment (estimated to be 2 months)]
- Changes in urine glucose [From start of treatment until end of treatment (estimated to be 2 months)]
- Changes in serum ketones [From start of treatment until end of treatment (estimated to be 2 months)]
- Changes in HbA1c [From baseline to Day 43]
- Changes in CT-based body composition (visceral fat) [From pre-therapy to post-8 weeks of therapy]
- Changes in CA19-9 [From pre-therapy to post-8 weeks of therapy]
- Changes in CT-quantified tumor size [From pre-therapy to post-8 weeks of therapy]
- Change in tumor necrosis [From pre-therapy to post-8 weeks of therapy]
- Objective response rate measured by RECIST 1.1 [At end of treatment (estimated to be 2 months)]
Objective response rate=number of complete and partial responses Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically or cytologically confirmed metastatic or locally advanced pancreatic ductal adenocarcinoma, pancreatic adenosquamous carcinoma or squamous cell carcinoma
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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.
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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.
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No prior systemic therapy for pancreatic ductal adenocarcinoma in the metastatic or locally advanced setting.
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Planning to receive treatment with nab-paclitaxel and gemcitabine.
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At least 18 years of age.
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ECOG performance status ≤ 1
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Normal bone marrow and organ function as defined below:
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Leukocytes ≥ 3,000/mcL
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Absolute neutrophil count ≥ 1,500/mcL
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Platelets ≥ 100,000/mcL
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Total bilirubin ≤ 1.5 x IULN
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AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
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Estimated glomerular filtration rate eGFR ≥ 30 mL/min/1.73m^2
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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
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Agreement to adhere to Lifestyle Considerations throughout study duration
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Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
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History of total pancreatectomy
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Current or previous treatment with SGLT2i or thiazolidinedione.
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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.
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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.
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History of stroke or transient ischemic attack (in the last 5 years).
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HbA1c > 10% unless approved by endocrinologist
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Currently receiving any other investigational agents.
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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.
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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.
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Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
- National Institutes of Health (NIH)
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Kian-Huat Lim, M.D., Washington University School of Medicine
Study Documents (Full-Text)
More Information
Publications
None provided.- 202011019
- 1P50CA196510-01A1