Pilot Project for Cardiopulmonary and Functional Evaluation in Patients With Pancreatic Cancer Associated Cachexia

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