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

NCT02775695 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO28944
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Month 3 visit

Study Arms (1)

Doxycycline Administered to Patients

EXPERIMENTAL

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

Drug: Doxycycline

Interventions

Doxycycline 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.

Also known as: Vibramycin, Doryx

Doxycycline Administered to Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Prior treatment with doxycycline within a seven day washout period prior to initiating treatment with alternate antimetakaryocidal medication.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Susan Tsai, MD
• Organization: Froedtert and the Medical College of Wisconsin

stsai@mcw.edu

414-805-9720

Study Officials

• Susan Tsai, MD, MHS

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 5, 2016
• First Posted: May 18, 2016
• Study Start: April 3, 2017
• Primary Completion: September 25, 2018
• Study Completion: May 26, 2022
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)