The Role of Muscle Cachexia in Pancreatic Cancer

NCT ID: NCT02515513

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2023-06-23

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.

Conditions

Pancreas Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Pancreatic Cancer Patients

During the surgical resection for the pancreatic cancer a muscle tissue biopsy sample will be performed.

Group Type: ACTIVE_COMPARATOR

Muscle Tissue Biopsy Sample

Intervention Type: PROCEDURE

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.

Surgical Patients with benign pathology

During surgical resection for patients with benign right upper quadrant pathology, a muscle tissue biopsy sample will be performed.

Group Type: ACTIVE_COMPARATOR

Muscle Tissue Biopsy Sample

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Pancreatic Cancer Patients who are potentially surgically resectable.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The V Foundation for Cancer Research

OTHER

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Judge, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

UF Health

Gainesville, Florida, United States

Countries

United States

References

Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009 Apr;89(2):381-410. doi: 10.1152/physrev.00016.2008.

Reference Type: BACKGROUND

PMID: 19342610 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18718696 (View on PubMed)

Other Identifiers

2R01AR060209-06A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB201500239 - N

Identifier Type: -

Identifier Source: org_study_id