Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer

Sponsor
Medical College of Wisconsin (Other)
Overall Status
Completed
CT.gov ID
NCT02775695
Collaborator
(none)
12
1
1
61.7
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Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

BACKGROUND AND RATIONALE:

Pancreatic tumors have two distinct cell populations -- eukaryotic tumor cells and metakaryotic cells. The first cell type divides quickly but must stop at a certain point. Metakaryotic cells, also called cancer stem cells, divide less frequently but have an unlimited number of cell divisions. Chemotherapy works well on eukaryotic cells. Metakaryotic cells are resistant to chemotherapy and radiation, so they are more difficult to eliminate.

Massachusetts Institute of Technology basic science researchers working with the Medical College of Wisconsin pancreatic cancer group demonstrated in the laboratory that doxycycline can kill both eukaryotic and metakaryotic cells.

This study's goal is to discover if the metakaryocidal drug doxycycline kills any significant fraction of the metakaryotic cells found in treated pancreatic tumors. Targeting metakaryotic cells may decrease cancer relapse and metastases. The development of antimetakaryotics is vital for pancreatic cancer patients, who are at risk for disease recurrence and cancer-related death.

STUDY OBJECTIVES:
Primary Objectives:

To assess the efficacy of doxycycline on inducing metakaryotic cell death in primary pancreatic tumors from patients with resectable pancreatic cancer.

Secondary Objectives:
  • To determine the plasma drug concentrations of the study drug at baseline and at days 1, 3, 5, 8, 15, 22, 29, and at restaging and at the time surgery.

  • To assess the histopathologic treatment response of the primary tumors which have undergone neoadjuvant gemcitabine based chemoradiation and concurrent doxycycline therapy.

  • To enumerate the number of observed dead/dying metakaryotes per 1 gram of resected pancreatic tissue.

STUDY PROCEDURES:

Patients will take 100 mg doxycycline twice daily for a period of eight weeks (56 days). Following standard-of-care (not study trial-related) chemotherapy, patients will receive radiation therapy. Patients will receive doxycycline beginning on the first day of radiation therapy. Following this, patients will undergo surgery four to five weeks after completion of chemoradiation. Doxycycline will be discontinued five to seven days prior to surgery.

This study involves pharmacokinetic studies, which means that patients will have blood draws several times so that serum levels may be evaluated.

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
Actual Study Start Date :
Apr 3, 2017
Actual Primary Completion Date :
May 26, 2022
Actual Study Completion Date :
May 26, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Doxycycline Administered to Patients

Patients will receive oral doxycycline and trough serum concentrations for pharmacokinetic studies will be obtained.

Drug: Doxycycline
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.
Other Names:
  • Vibramycin
  • Doryx
  • Outcome Measures

    Primary Outcome Measures

    1. Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response [Three months]

      Cytopathologists will evaluate each patient sample. In addition, the histopathologic response of the primary tumor will be assessed using the College of American Pathology criteria for residual tumor response following neoadjuvant therapy for the exocrine pancreas. Researchers will enumerate the number of observed dead/dying metakaryotes per 1 gram of resected pancreatic tissue.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Medical College of Wisconsin Milwaukee Wisconsin United States 53226

    Sponsors and Collaborators

    • Medical College of Wisconsin

    Investigators

    • Principal Investigator: Susan Tsai, MD, MHS, Medical College of Wisconsin

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Susan Tsai, Professor, Medical College of Wisconsin
    ClinicalTrials.gov Identifier:
    NCT02775695
    Other Study ID Numbers:
    • PRO28944
    First Posted:
    May 18, 2016
    Last Update Posted:
    Aug 2, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Susan Tsai, Professor, Medical College of Wisconsin
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 2, 2022