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

NCT ID: NCT02775695

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-03
• Study Completion Date: 2022-05-26

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.

Conditions

Resectable Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doxycycline Administered to Patients

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

Group Type: EXPERIMENTAL

Doxycycline

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Vibramycin; Doryx

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Susan Tsai

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Susan Tsai, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

PRO28944

Identifier Type: -

Identifier Source: org_study_id