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The Role of Muscle Cachexia in Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT02515513
Recruitment Status : Recruiting
First Posted : August 4, 2015
Last Update Posted : October 26, 2018
Sponsor:
Collaborators:
The V Foundation for Cancer Research
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of Florida

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.


Condition or disease Intervention/treatment Phase
Pancreas Cancer Procedure: Muscle Tissue Biopsy Sample Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Role of Muscle Cachexia in Pancreatic Cancer
Study Start Date : March 2016
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Pancreatic Cancer Patients
During the surgical resection for the pancreatic cancer a muscle tissue biopsy sample will be performed.
Procedure: Muscle Tissue Biopsy Sample
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.

Active Comparator: Surgical Patients with benign pathology
During surgical resection for patients with benign right upper quadrant pathology, a muscle tissue biopsy sample will be performed.
Procedure: Muscle Tissue Biopsy Sample
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 Measures :
  1. Ultrastructural abnormalities in muscle tissue samples between the groups [ Time Frame: day 1 ]
    To look at the extent of ultrastructural abnormalities in the skeletal muscle by histologic examination of muscle biopsies

  2. Myofiber atrophy in muscle tissue samples between the groups [ Time Frame: day 1 ]
    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.

  3. Identify gene networks within the skeletal muscle between the groups [ Time Frame: day 1 ]
    RT-PCR of RNA from biopsied muscle tissues


Secondary Outcome Measures :
  1. History of weight lost [ Time Frame: Baseline ]
    Clinical assessment at treatment follow-up

  2. Nutritional status [ Time Frame: Approximately 2 years ]
    Clinical assessment at treatment follow-up

  3. Blood Chemistry composite [ Time Frame: Approximately 2 years ]
    Clinical assessment at treatment follow-up

  4. Preoperative sarcopenia using a muscular index [ Time Frame: Approximately 2 years ]
    Clinical assessment at treatment follow-up and radiographic measurements of muscle groups on routine surveillance for cancer recurrence or advancement

  5. Measurement of lymphatic metastasis [ Time Frame: Approximately 2 years ]
    Pathologic specimen at time of resection to determine extent of pathologic stage which is routine

  6. Tumor grade [ Time Frame: Approximately 2 years ]
    Noted at pathologic assessment and part of routine examination

  7. Survival data [ Time Frame: Approximately 2 years ]
    Noted on routine follow-up



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pancreatic Cancer Patients who are potentially surgically resectable.

Exclusion Criteria:

  • Patients who do not meet the criteria for surgical resection.

Information from the National Library of Medicine

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): NCT02515513


Contacts
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Contact: Jose G Trevino, MD 352-266-0761 jose.trevino@surgery.ufl.edu
Contact: Amber M Bouton, BA/CCRP/CCRC 352-594-9572

Locations
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United States, Florida
UF Health Recruiting
Gainesville, Florida, United States, 32611
Contact: Jose Trevino, MD    352-265-0761    jose.trevino@surgery.ufl.edu   
Contact: Amber M Bouton, CCRP/CCRC    352-594-9572    amber.bouton@surgery.ufl.edu   
Sponsors and Collaborators
University of Florida
The V Foundation for Cancer Research
National Institutes of Health (NIH)
Investigators
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Principal Investigator: Jose G Trevino, MD University of Florida

Publications:
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02515513     History of Changes
Other Study ID Numbers: IRB201500239 - N
P0038174 [pending] ( Other Grant/Funding Number: National Institute of Health )
First Posted: August 4, 2015    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:
Pancreas
Pancreas Cancer
Muscle Biopsy
Cachexia
Muscle Cachexia

Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Wasting Syndrome
Cachexia
Digestive System Diseases
Endocrine System Diseases
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Metabolic Diseases
Nutrition Disorders