Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition

NCT ID: NCT04542291

Last Updated: 2023-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-25
• Study Completion Date: 2022-01-19

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.

Conditions

Pancreas Cancer; Pancreatic Cancer; Cancer of the Pancreas

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Dapagliflozin

Intervention Type: DRUG

Dapagliflozin will be provided for this trial

BIOSENSE meters

Intervention Type: DEVICE

-Being used in this trial to evaluate utility for assessing breath ketones

Interventions

Dapagliflozin

Dapagliflozin will be provided for this trial

Intervention Type: DRUG

BIOSENSE meters

-Being used in this trial to evaluate utility for assessing breath ketones

Intervention Type: DEVICE

Other Intervention Names

Farxiga

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kian-Huat Lim, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

Park LK, Lim KH, Volkman J, Abdiannia M, Johnston H, Nigogosyan Z, Siegel MJ, McGill JB, McKee AM, Salam M, Zhang RM, Ma D, Popuri K, Chow VTY, Beg MF, Hawkins WG, Peterson LR, Ippolito JE. Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study. Cancer Metab. 2023 May 18;11(1):6. doi: 10.1186/s40170-023-00306-2.

Reference Type: DERIVED

PMID: 37202813 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

1P50CA196510-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202011019

Identifier Type: -

Identifier Source: org_study_id