Efficacy of Doxycycline on Metakaryote Cell Death in Patients With Resectable Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT02775695|
Recruitment Status : Active, not recruiting
First Posted : May 18, 2016
Last Update Posted : November 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Resectable Pancreatic Cancer||Drug: Doxycycline||Phase 2|
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.
To assess the efficacy of doxycycline on inducing metakaryotic cell death in primary pancreatic tumors from patients with resectable pancreatic cancer.
- 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.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
Experimental: Doxycycline Administered to Patients
Patients will receive oral doxycycline and trough serum concentrations for pharmacokinetic studies will be obtained.
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.
- 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.
- 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.)
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
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Principal Investigator:||Susan Tsai, MD, MHS||Medical College of Wisconsin|