Pilot Project for Cardiopulmonary and Functional Evaluation in Patients With Pancreatic Cancer Associated Cachexia
Pilot Project for Cardiopulmonary and Functional Evaluation in Patients With Pancreatic Cancer Associated Cachexia
Cachexia is a systemic catabolic syndrome with apparent effect on skeletal muscles, tolerance
 to chemotherapy, early toxicity and quality of life; however, its effect on cardiopulmonary
 function is not well understood. Preclinical studies demonstrated diaphragmatic muscle
 wasting(29) and left ventricular wasting and fibrosis associated with mouse cachexia
 models.(40) Many patients, who experience cancer cachexia, describe a generalized debility
 and a sense of breathlessness(41) despite adequate oxygenation in the peripheral blood as
 measured by pulse oximetry. Whether this is related to deconditioning associated with
 chemotherapy or related to direct effect on cardiac and diaphragmatic muscles remains
 unknown. In this pilot study, the investigators propose to perform a preliminary evaluation
 of the cardiopulmonary function in patients with pancreatic cancer, who are likely to develop
 cachexia, to assess for the feasibility of performing a larger prospective study to
 understand the impact of cancer cachexia on cardiopulmonary function. This pilot study will
 provide the foundation to potentially identify cachexia in early stages (pre-cachexia) to
 develop pharmacological or exercise based interventions to prevent or delay its progression.
 Based on clinical experience and published literature, it is expected that 60-70% of patients
 will have >10% weight loss during the course of this disease. More commonly, this is
 associated with clinical or radiographic disease progression, but certainly it can happen
 throughout the course of the disease even without disease progression.
Primary Objective:

 To assess the feasibility of performing a prospective cardiopulmonary and physical function
 assessment in patients with advanced pancreatic ductal adenocarcinoma (PDAC) who are expected
 to develop cachexia.

 Secondary Objectives:

 1. To measure the changes in maximal expiratory pressure (MEP) and maximal inspiratory
 pressure (MIP) in patients with progressive PDAC and/or cancer associated cachexia

 2. To measure changes in strain echocardiography in patients with progressive PDAC and/or
 cancer associated cachexia

 3. To assess functional changes in patients with progressive PDAC and/or cancer associated
 cachexia

 4. To assess body composition changes associated with cachexia or disease progression

 5. To measure the levels of cytokines from peripheral blood in patients with cachexia

 Procedures:

 All study procedures will be done at two time points (T1=baseline or study entry, T2=at
 disease progression or development of cachexia). Patients will undergo echocardiography with
 strain evaluation at Indiana University Health Echocardiography Laboratory and pulmonary
 function tests as per institutional guidelines at IUH PFT laboratory at University Hospital.
 Patients will also have 20mL (2 red top tubes) of blood drawn for the studies outlined in
 Section 7.5. Standard of care labs will be taken from the patient's medical records. Patients
 also will be evaluated using three standardized functional assessment tools commonly utilized
 in physical rehabilitation: 1) 5 Times Sit-to-Stand Test; 2) 6 Minute Walk Test; and 3) grip
 dynamometry. Standard of care CT scan obtained at the time of tumor assessment will enable
 the investigators to assess body muscle mass as described in Section 7.4. In addition, the
 investigators will administer three standardized survey tools to assess quality of life and
 prior level of function: 1) The Short Form 36 (SF-36); 2) Lower Extremity Functional Scale
 (LEFS); and 3) Scored Patient-Generated Subjective Global Assessment (PG-SGA).

 Sample Size:

 Due to the risk of clinical deterioration or drop out of the study and inability to undergo
 T2 evaluation, the investigators will plan on enrolling 133% of desired number of subjects,
 accounting for 33% missing T2 data. This is likely a high number; however, this will enable
 data collection from 12-15 patients at both time points and all proposed tests.
Inclusion Criteria:

 1. Patients with locally advanced, metastatic or recurrent pancreatic ductal
 adenocarcinoma (PDAC)

 2. Patients who are being treated and/or followed at Indiana University Simon Cancer
 Center or Eskenazi Hospital

 3. ECOG PS 0-2 at the time of study enrollment

 4. Life expectancy > 6 months

 5. Adequate organ function

 -  As defined by the following laboratory values at study entry:

 -  Hemoglobin ≥ 9 g/dL (transfusions are acceptable)

 -  ANC ≥ 1.5 x 109/L

 -  Platelets ≥ 100 x 109/L

 -  Creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 50 mL/min (estimated by
 Cockcroft-Gault or measured)

 -  Total bilirubin ≤ 1.5 x ULN

 -  AST/ALT ≤ 3 x ULN

 6. Willingness to sign informed consent and to perform pulmonary function tests (PFTs)
 and strain echocardiogram

 Exclusion Criteria:

 1. Known history of congestive heart failure (NYHA class III or IV)

 2. Reported weight loss more than 10% within 3 months prior to study entry

 3. Known history of pulmonary disease such as pulmonary hypertension, chronic obstructive
 pulmonary disease requiring medical management or previous lung resection

 4. Current liver cirrhosis

 5. Current chronic kidney disease

 6. Inability or refusal to receive systemic therapy

 7. Inability to comply with pulmonary function tests (PFTs)

 8. Large volume ascites interfering with ability of respiration

 9. Current unstable angina (or history of within last 6 months)

 10. Recent myocardial infraction (within last 6 months)

 11. Recent pneumothorax (within last 6 months)

 12. Uncontrolled hypertension (per investigator's discretion)

 13. Lung biopsy within one week from PFT

 14. Recent surgery < 4 weeks