Clinical Trials /

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

NCT04542291

Description:

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.

Related Conditions:
  • Pancreatic Adenosquamous Carcinoma
  • Pancreatic Ductal Adenocarcinoma
  • Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition
  • Official Title: Targeting Pancreatic Cancer With Sodium Glucose Transporter 2 (SGLT2) Inhibition

Clinical Trial IDs

  • ORG STUDY ID: 20-x315
  • SECONDARY ID: 1P50CA196510-01A1
  • NCT ID: NCT04542291

Conditions

  • Pancreas Cancer
  • Pancreatic Cancer
  • Cancer of the Pancreas

Interventions

DrugSynonymsArms
DapagliflozinFarxigaDapagliflozin

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DapagliflozinExperimentalDapagliflozin is an oral drug which will be administered on an outpatient basis. Dosing will start at 5 mg QD and will increase to 10 mg QD after 2 weeks 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.
  • Dapagliflozin

Eligibility Criteria

        Inclusion Criteria:

          -  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).

        Exclusion Criteria:

          -  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
             carcinoma.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tolerability as measured by incidence of adverse events measured by CTCAE v. 5.0
Time Frame:From start of treatment through 30 days after treatment (estimated to be 3 months)
Safety Issue:
Description:-Adverse events will be graded with CTCAE v. 5.0.

Secondary Outcome Measures

Measure:Changes in plasma glucose
Time Frame:From start of treatment until end of treatment (estimated to be 2 months)
Safety Issue:
Description:
Measure:Changes in urine glucose
Time Frame:From start of treatment until end of treatment (estimated to be 2 months)
Safety Issue:
Description:
Measure:Changes in serum ketones
Time Frame:From start of treatment until end of treatment (estimated to be 2 months)
Safety Issue:
Description:
Measure:Changes in HbA1c
Time Frame:From baseline to Day 43
Safety Issue:
Description:
Measure:Changes in CT-based body composition (visceral fat)
Time Frame:From pre-therapy to post-8 weeks of therapy
Safety Issue:
Description:
Measure:Changes in CA19-9
Time Frame:From pre-therapy to post-8 weeks of therapy
Safety Issue:
Description:
Measure:Changes in CT-quantified tumor size
Time Frame:From pre-therapy to post-8 weeks of therapy
Safety Issue:
Description:
Measure:Change in tumor necrosis
Time Frame:From pre-therapy to post-8 weeks of therapy
Safety Issue:
Description:
Measure:Objective response rate measured by RECIST 1.1
Time Frame:At end of treatment (estimated to be 2 months)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

September 8, 2020