Back to resultsEfficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
Primary Purpose
Resectable Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Doxycycline
Sponsored by
About this trial
This is an interventional treatment trial for Resectable Pancreatic Cancer focused on measuring pancreatic cancer, Resectable Pancreatic Cancer, Doxycycline, Metakaryote cells, Eukaryotic cells, Cancer Stem Cells, Targeted Cancer Stem Cell Therapy, Multi-metakaryocide therapy, Doxycycline Hyclate, Tetracycline
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:
- leukocytes ≥3,000/microliter (mcL)
- absolute neutrophil count ≥1,500/mcL
- platelets ≥100,000/mcL
- total bilirubin < 2 mg/dL or has demonstrated progressive decline within two weeks of biliary decompression to allow for appropriate gemcitabine dose modification.
- Aspartate Aminotransferase (AST)[Serum Glutamic Oxaloacetic Transaminase (SGOT] )/ Alanine Aminotransferase (ALT) [Serum Glutamic Pyruvic Transaminase(SGPT)] ≤3 × institutional upper limit of normal
- 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.
Sites / Locations
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Doxycycline Administered to Patients
Arm Description
Patients will receive oral doxycycline and trough serum concentrations for pharmacokinetic studies will be obtained.
Outcomes
Primary Outcome Measures
Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response
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
Full Information
NCT ID
NCT02775695
First Posted
May 5, 2016
Last Updated
June 14, 2023
Sponsor
Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT02775695
Brief Title
Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
Official Title
Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 3, 2017 (Actual)
Primary Completion Date
September 25, 2018 (Actual)
Study Completion Date
May 26, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin
4. Oversight
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
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resectable Pancreatic Cancer
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Doxycycline Administered to Patients
Arm Type
Experimental
Arm Description
Patients will receive oral doxycycline and trough serum concentrations for pharmacokinetic studies will be obtained.
Intervention Type
Drug
Intervention Name(s)
Doxycycline
Other Intervention Name(s)
Vibramycin, Doryx
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.
Primary Outcome Measure Information:
Title
Determine the Efficacy of Doxycycline in Inducing Metakaryotic Cell Death in Primary Pancreatic Tumors as Measured by Pathologic Response
Description
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.
Time Frame
Month 3 visit
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
leukocytes ≥3,000/microliter (mcL)
absolute neutrophil count ≥1,500/mcL
platelets ≥100,000/mcL
total bilirubin < 2 mg/dL or has demonstrated progressive decline within two weeks of biliary decompression to allow for appropriate gemcitabine dose modification.
Aspartate Aminotransferase (AST)[Serum Glutamic Oxaloacetic Transaminase (SGOT] )/ Alanine Aminotransferase (ALT) [Serum Glutamic Pyruvic Transaminase(SGPT)] ≤3 × institutional upper limit of normal
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Tsai, MD, MHS
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
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