Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 50 of 1594 for:    Pancreatic Cancer | United States

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02775695
Recruitment Status : Active, not recruiting
First Posted : May 18, 2016
Last Update Posted : November 7, 2018
Sponsor:
Information provided by (Responsible Party):
Susan Tsai, Medical College of Wisconsin

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
Resectable Pancreatic Cancer Drug: Doxycycline 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
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 : April 3, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : July 2023


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.




Primary Outcome Measures :
  1. Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response [ Time Frame: 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.


Secondary Outcome Measures :
  1. Determine the Plasma Drug Concentrations of the Study Drug from Scheduled Patient Blood Draws Using Mass Spectrometry [ Time Frame: Nine Weeks ]

    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, 29 and at restaging imaging to assess drug compliance and a final level will be checked at the time surgery. Plasma will be checked using mass spectrometry. Twelve serial samples will be acquired for each patient. The data regarding serum concentrations of doxycycline will be reported to the data manager.

    (Treatment Plan: Doxycycline hyclate 100 mg PO Q12 hours will be administered to the patient for a period of 8 weeks (56 days) starting on the first day of radiation therapy. Restaging imaging with either pancreatic protocol CT or MRI will be performed week 8 to assess disease status. Patients will generally undergo surgery week 9. Doxycycline will be discontinued 5-7 days prior to surgery.)




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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/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. AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
    6. Creatinine clearance ≥60 mL/min/1.73 m2

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02775695


Locations
Layout table for location information
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Medical College of Wisconsin
Investigators
Layout table for investigator information
Principal Investigator: Susan Tsai, MD, MHS Medical College of Wisconsin

Layout table for additonal information
Responsible Party: Susan Tsai, Assistant Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT02775695     History of Changes
Other Study ID Numbers: PRO26988
First Posted: May 18, 2016    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
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, Medical College of Wisconsin:
pancreatic cancer
Resectable Pancreatic Cancer
Doxycycline
Metakaryote cells
Eukaryotic cells
Cancer Stem Cells
Targeted Cancer Stem Cell Therapy
Multi-metakaryocide therapy
Doxycycline Hyclate
Tetracycline

Additional relevant MeSH terms:
Layout table for MeSH terms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Digestive System Diseases
Endocrine System Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents