The Role of Muscle Cachexia in Pancreatic Cancer
Primary Purpose
Pancreas Cancer
Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Muscle Tissue Biopsy Sample
Sponsored by
About this trial
This is an interventional basic science trial for Pancreas Cancer focused on measuring Pancreas, Pancreas Cancer, Muscle Biopsy, Cachexia, Muscle Cachexia
Eligibility Criteria
Inclusion Criteria:
- Pancreatic Cancer Patients who are potentially surgically resectable.
Exclusion Criteria:
- Patients who do not meet the criteria for surgical resection.
Sites / Locations
- UF Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Pancreatic Cancer Patients
Surgical Patients with benign pathology
Arm Description
During the surgical resection for the pancreatic cancer a muscle tissue biopsy sample will be performed.
During surgical resection for patients with benign right upper quadrant pathology, a muscle tissue biopsy sample will be performed.
Outcomes
Primary Outcome Measures
Ultrastructural abnormalities in muscle tissue samples between the groups
To look at the extent of ultrastructural abnormalities in the skeletal muscle by histologic examination of muscle biopsies
Myofiber atrophy in muscle tissue samples between the groups
2) identify the growth and atrophy-related transcription factors associated with the muscle pathology and 3) identify the genome-wide gene networks and biological process associated with skeletal muscle pathology in surgically resected PC patients and healthy control patients by RT-PCR and histologic staining of tissues for transcriptional factors associated with cachexia.
Identify gene networks within the skeletal muscle between the groups
RT-PCR of RNA from biopsied muscle tissues
Secondary Outcome Measures
History of weight lost
Clinical assessment at treatment follow-up
Nutritional status
Clinical assessment at treatment follow-up
Blood Chemistry composite
Clinical assessment at treatment follow-up
Preoperative sarcopenia using a muscular index
Clinical assessment at treatment follow-up and radiographic measurements of muscle groups on routine surveillance for cancer recurrence or advancement
Measurement of lymphatic metastasis
Pathologic specimen at time of resection to determine extent of pathologic stage which is routine
Tumor grade
Noted at pathologic assessment and part of routine examination
Survival data
Noted on routine follow-up
Full Information
NCT ID
NCT02515513
First Posted
June 3, 2015
Last Updated
June 26, 2023
Sponsor
University of Florida
Collaborators
The V Foundation for Cancer Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1. Study Identification
Unique Protocol Identification Number
NCT02515513
Brief Title
The Role of Muscle Cachexia in Pancreatic Cancer
Official Title
The Role of Muscle Cachexia in Pancreatic Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Original PI left the institution. No subjects enrolled
Study Start Date
March 2016 (undefined)
Primary Completion Date
June 23, 2023 (Actual)
Study Completion Date
June 23, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
The V Foundation for Cancer Research, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The relationship between myopenia, nutritional status, and long-term oncologic outcomes remains poorly characterized in patients with anatomically resectable pancreatic cancer (PC). The investigators want to look at muscle properties in pancreatic cancer patients to determine possible therapeutic options toward better nutritional status. Patients with benign right upper quadrant pathology will be utilized as controls for the study.
The researchers hypothesize that improving cancer cachexia in PC will improve the quality of life and ultimately increase overall survival. The long term goal of is to identify areas of intervention to prevent and/or improve cachectic events in PC in order to significantly improve clinical outcomes. The first step in this long term goal is to fully characterize cachexia in the condition of PC. This research is to understand and modify the local response within skeletal muscle leading to a clinically relevant persistent wasting and to understand and interrupt the systemic stimulus produced by the tumor local environment resulting in these muscle specific mechanisms.
Detailed Description
Cancer cachexia (CC) is a devastating condition affecting up to 80% of cancer patients, diminishing quality of life and contributing to increased mortality. Cancer cachexia is a complex metabolic syndrome characterized by the loss of skeletal muscle mass and weakness. The muscle pathology of cancer cachexia is not only related to muscle atrophy but also to disruptions to the contractile apparatus of the muscle. While physiologic disruptions in muscle sarcomere and myofiber membrane integrity have been observed despite the lack of injury, the totality of the muscle specific mechanisms contributing to these phenotypes have not been described, nor investigated in the context of pancreatic cancer (PC) where cachexia is a significant clinical problem. Therefore, delineating specific mechanisms of muscle catabolism in PC is critical to developing clinical therapies to control wasting and improve patient quality of life, clinical outcomes and long-term survival.
A variety of tumor promoting and inflammatory cell signaling pathways have been implicated in cancer cachexia, whereby pro-inflammatory cytokines have been implicated as a driving force. Remarkably, approximately half of all patients with PC demonstrate a measurable acute phase response, which is associated with poor clinical outcomes. Importantly, systemic elevations of these inflammatory mediators are due to a complex local interplay between the developing tumor and the immune system which subsequently leads to a systemic chronic inflammatory state. PC appears to manipulate the immune system to promote its survival at the expense of nutritional stores which results in cachexia. Therefore, understanding of the local and systemic inflammatory response in PC and its relation to muscle specific mechanisms is crucial to developing effective therapies for cancer cachexia.
PC associated cachexia results in a significant therapeutic dilemma. Local approaches such as surgery for curative intent encounter a high recurrence rate which is indicative of the systemic nature of even very early-stage disease. Therefore, systemic therapies are necessary for long-term survival. Unfortunately, effective chemotherapies are only offered to patients with good clinical parameters such as nutritional status. In other words, if the patient is too weak, they are not offered effective therapies for the risk of causing more harm than good.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer
Keywords
Pancreas, Pancreas Cancer, Muscle Biopsy, Cachexia, Muscle Cachexia
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pancreatic Cancer Patients
Arm Type
Active Comparator
Arm Description
During the surgical resection for the pancreatic cancer a muscle tissue biopsy sample will be performed.
Arm Title
Surgical Patients with benign pathology
Arm Type
Active Comparator
Arm Description
During surgical resection for patients with benign right upper quadrant pathology, a muscle tissue biopsy sample will be performed.
Intervention Type
Procedure
Intervention Name(s)
Muscle Tissue Biopsy Sample
Intervention Description
During surgical resection, to enter the abdominal cavity, anterior muscle groups such as the rectus abdominous muscle. This group of muscle is divided. During division, muscle fibers are released from fascial group and discarded off the operative field. This will be the target for specimen collection.
Primary Outcome Measure Information:
Title
Ultrastructural abnormalities in muscle tissue samples between the groups
Description
To look at the extent of ultrastructural abnormalities in the skeletal muscle by histologic examination of muscle biopsies
Time Frame
day 1
Title
Myofiber atrophy in muscle tissue samples between the groups
Description
2) identify the growth and atrophy-related transcription factors associated with the muscle pathology and 3) identify the genome-wide gene networks and biological process associated with skeletal muscle pathology in surgically resected PC patients and healthy control patients by RT-PCR and histologic staining of tissues for transcriptional factors associated with cachexia.
Time Frame
day 1
Title
Identify gene networks within the skeletal muscle between the groups
Description
RT-PCR of RNA from biopsied muscle tissues
Time Frame
day 1
Secondary Outcome Measure Information:
Title
History of weight lost
Description
Clinical assessment at treatment follow-up
Time Frame
Baseline
Title
Nutritional status
Description
Clinical assessment at treatment follow-up
Time Frame
Approximately 2 years
Title
Blood Chemistry composite
Description
Clinical assessment at treatment follow-up
Time Frame
Approximately 2 years
Title
Preoperative sarcopenia using a muscular index
Description
Clinical assessment at treatment follow-up and radiographic measurements of muscle groups on routine surveillance for cancer recurrence or advancement
Time Frame
Approximately 2 years
Title
Measurement of lymphatic metastasis
Description
Pathologic specimen at time of resection to determine extent of pathologic stage which is routine
Time Frame
Approximately 2 years
Title
Tumor grade
Description
Noted at pathologic assessment and part of routine examination
Time Frame
Approximately 2 years
Title
Survival data
Description
Noted on routine follow-up
Time Frame
Approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pancreatic Cancer Patients who are potentially surgically resectable.
Exclusion Criteria:
Patients who do not meet the criteria for surgical resection.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Judge, PhD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
UF Health
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
19342610
Citation
Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009 Apr;89(2):381-410. doi: 10.1152/physrev.00016.2008.
Results Reference
background
PubMed Identifier
18718696
Citation
Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD. Cachexia: a new definition. Clin Nutr. 2008 Dec;27(6):793-9. doi: 10.1016/j.clnu.2008.06.013. Epub 2008 Aug 21.
Results Reference
background
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The Role of Muscle Cachexia in Pancreatic Cancer
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