Back to resultsBiological Effect of Warfarin on Pancreatic Cancer
Primary Purpose
Pancreatic Cancer
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Warfarin
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Cancer
Eligibility Criteria
Inclusion Criteria:
- Pathologically-confirmed, localized or metastatic adenocarcinoma of the pancreas. Diagnostic biopsy must be obtained at the study institution prior to enrollment. Pathology material must be available for review.
- Patient must have measurable disease per RECIST criteria
- Started most recent systemic therapy regimen within 15 days of enrollment (any line of therapy is allowed).
- Ability to tolerate, swallow and absorb oral medications.
- Ability to understand and the willingness to sign a written informed consent.
- Age > 18 years
- Negative blood pregnancy test within seven days of study entry for WOCBP
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
- Active radiation therapy, or planned radiation therapy during study period
- Subjects may not be receiving any other investigational agents.
- Pregnant, nursing or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be potentially teratogenic.
- Underlying condition which may increase the risk of complications from warfarin therapy. These can include:
Known major bleeding diathesis:
- Coagulopathy
- Significant GI bleed within 6 months,
- Clinically significant hematuria or hemoptysis,
- Thrombolytic therapy within one month of study entry,
- Active peptic ulcer disease with bleeding. - Significant infection or other coexistent medical condition that would preclude protocol therapy 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
Sites / Locations
- University of Texas Southwestern Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Warfarin
Arm Description
Patients will be assigned to warfarin by mouth daily on an outpatient basis. Dose level will increase after 5 patients enrolled. Dose 1 = 1 mg warfarin; Dose 2 = 2 mg warfarin; Dose 3 = 2.5 mg warfarin; Dose 4 = 4 mg warfarin and Dose 5 = 5 mg warfarin
Outcomes
Primary Outcome Measures
Determine change in AXL pathway
Determine change in circulating biomarkers of AXL pathways (including phosphogas6, soluble AXL).
Secondary Outcome Measures
Assess adverse events
Assess the adverse events (per CTCAE v4.0 criteria) associated with the addition of warfarin in patients with pancreatic cancer receiving chemotherapy.
Effect of warfarin on tissue markers
Evaluate the effect of warfarin on tissue markers of the AXL pathways measured by western blot analysis in tumor tissue and expression levels of EMY markers following warfarin therapy.
Antitumor effect
Antitumor effects will be observed by change in CA9-19 levels pre and post warfarin. therapy.
Full Information
NCT ID
NCT03536208
First Posted
March 28, 2018
Last Updated
March 23, 2021
Sponsor
University of Texas Southwestern Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03536208
Brief Title
Biological Effect of Warfarin on Pancreatic Cancer
Official Title
Biological Effect of Warfarin on Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Withdrawn
Why Stopped
no accrual for over 12 months
Study Start Date
May 15, 2019 (Actual)
Primary Completion Date
June 2021 (Anticipated)
Study Completion Date
June 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
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 study aims to asses the effect of warfarin on markers of AXL pathway in patients with pancreatic adenocarcinoma.
Detailed Description
There is emerging evidence from pre-clinical models that Axl activation is critical for the tumorigenesis and metastasis of pancreatic cancer. Warfarin is a readily available drug in the clinical setting and could be easily, safely, and quickly used in patients in combination with known cytotoxic chemotherapies to improve overall survival.
Oral warfarin has been well tolerated in both prophylaxis for catheter-associated thrombosis and in advanced pancreatic cancer patients.
The aim of this trial is to confirm the preclinical evidence that warfarin affects AXL pathway in patients with pancreatic cancer. This will validate the effect of escalating doses of warfarin on circulating biomarkers of AXL.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Model Description
patients will be assigned to warfarin by mouth daily on an outpatient basis. The first 5 patients enrolled will be assigned to the 1 mg QD dose level, the next 5 patients enrolled will be assigned to the 2 mg QD dose level, and so forth until all dose levels enrolled 5 patients.
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Warfarin
Arm Type
Experimental
Arm Description
Patients will be assigned to warfarin by mouth daily on an outpatient basis. Dose level will increase after 5 patients enrolled. Dose 1 = 1 mg warfarin; Dose 2 = 2 mg warfarin; Dose 3 = 2.5 mg warfarin; Dose 4 = 4 mg warfarin and Dose 5 = 5 mg warfarin
Intervention Type
Drug
Intervention Name(s)
Warfarin
Intervention Description
5 different doses of warfarin will be assigned, ranging from 1mg to 5 mg.
Primary Outcome Measure Information:
Title
Determine change in AXL pathway
Description
Determine change in circulating biomarkers of AXL pathways (including phosphogas6, soluble AXL).
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Assess adverse events
Description
Assess the adverse events (per CTCAE v4.0 criteria) associated with the addition of warfarin in patients with pancreatic cancer receiving chemotherapy.
Time Frame
30 days
Title
Effect of warfarin on tissue markers
Description
Evaluate the effect of warfarin on tissue markers of the AXL pathways measured by western blot analysis in tumor tissue and expression levels of EMY markers following warfarin therapy.
Time Frame
30 days
Title
Antitumor effect
Description
Antitumor effects will be observed by change in CA9-19 levels pre and post warfarin. therapy.
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically-confirmed, localized or metastatic adenocarcinoma of the pancreas. Diagnostic biopsy must be obtained at the study institution prior to enrollment. Pathology material must be available for review.
Patient must have measurable disease per RECIST criteria
Started most recent systemic therapy regimen within 15 days of enrollment (any line of therapy is allowed).
Ability to tolerate, swallow and absorb oral medications.
Ability to understand and the willingness to sign a written informed consent.
Age > 18 years
Negative blood pregnancy test within seven days of study entry for WOCBP
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
Active radiation therapy, or planned radiation therapy during study period
Subjects may not be receiving any other investigational agents.
Pregnant, nursing or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be potentially teratogenic.
Underlying condition which may increase the risk of complications from warfarin therapy. These can include:
Known major bleeding diathesis:
Coagulopathy
Significant GI bleed within 6 months,
Clinically significant hematuria or hemoptysis,
Thrombolytic therapy within one month of study entry,
Active peptic ulcer disease with bleeding. - Significant infection or other coexistent medical condition that would preclude protocol therapy 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Muhammad S Beg, MD
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-9179
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Biological Effect of Warfarin on Pancreatic Cancer
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