Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
Condition: Resectable Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: Doxycycline
Intervention description: Treatment with doxycycline hyclate will be administered as an oral agent on an outpatient basis. Patients will receive doxycycline 100 mg twice daily for a period of 8 weeks (56 days). Upon registration (baseline) and at the first, third, and fifth days of doxycycline therapy, patients will be seen to obtain trough serum concentrations for pharmacokinetic studies. Additional serum levels will be checked on days 8, 15, 22 and 29.
Intervention MeSH terms: Doxycycline
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: pancreatic cancer; Resectable Pancreatic Cancer; Doxycycline; Metakaryote cells; Eukaryotic cells; Cancer Stem Cells; Targeted Cancer Stem Cell Therapy; Multi-metakaryocide therapy; Doxycycline Hyclate; Tetracycline

Summary:

      This is a window-of-opportunity study that examines the efficacy of doxycycline, and
      FDA-approved oral antibiotic, on metakaryotic (cancer stem cells) in resectable pancreatic
      cancer following eight weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed pancreatic adenocarcinoma which may be
             acquired using a fine needle aspiration.

          -  Not received any prior therapy.

          -  Established resectable pancreatic cancer based on radiographic imaging.

          -  Patients who will receive neoadjuvant therapy (chemoradiation) are eligible.

          -  Age ≥18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%).

          -  Have no active or chronic infection with HIV, Hepatitis B or Hepatitis C

          -  Life expectancy of greater than six months.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Normal organ and marrow function as defined below:

               1. leukocytes ≥3,000/microliter (mcL)

               2. absolute neutrophil count ≥1,500/mcL

               3. platelets ≥100,000/mcL

               4. total bilirubin < 2 mg/dL or has demonstrated progressive decline within two
                  weeks of biliary decompression to allow for appropriate gemcitabine dose
                  modification.

               5. Aspartate Aminotransferase (AST)[Serum Glutamic Oxaloacetic Transaminase (SGOT]
                  )/ Alanine Aminotransferase (ALT) [Serum Glutamic Pyruvic Transaminase(SGPT)] ≤3
                  × institutional upper limit of normal

               6. Creatinine clearance ≥60 mL/min/1.73 m^2

        Exclusion Criteria:

          -  Patients with more clinically advanced pancreatic cancer (borderline resectable,
             locally advanced, or metastatic).

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because the effects of metakaryocidal
             agents have the potential for teratogenic or abortifacient effects.

          -  Previous history of other malignancy (other than cured basal or squamous cell
             carcinoma of the skin or cured in-situ carcinoma of the cervix) within two years of
             study enrollment.

          -  Active or chronic HIV, hepatitis B or hepatitis C.

          -  Patients who are receiving other investigational drugs or enrolled in other clinical
             trials.

          -  Inability to undergo scheduled blood acquisition per protocol.

          -  Drug specific exclusion including history of allergic reactions to tetracyclines.

          -  Prior treatment with doxycycline within a seven day washout period prior to initiating
             treatment with alternate antimetakaryocidal medication.