Cardiopulmonary Exercise Testing: An Assessment of Patients Fitness for Palliative Chemotherapy for Pancreatic Cancer (CPET-Panc)

CPET-Panc: Exercise Testing in Chemotherapy

Cardiopulmonary exercise testing (CPET) has been shown to be superior to American Society of Anaesthetist classification (ASA) in predicting peri-operative risk. The most common performance status used is the World Health Organisation (WHO) (0-4), with a clinician agreed differentiation of the subsets of 0-2 and 3-4; variability also exists within these subsets.

With this there rises a concern that fit older patients may not be offered appropriate chemotherapy treatment. This observational study will assess whether cardiopulmonary exercise testing (CPET) offers additional benefit over that of WHO Performance status (PS) in the assessment of patients fitness for palliative chemotherapy for pancreatic cancer, by identifying those patients who might survive longer and tolerate chemotherapy better, thus predicting their outcome.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Device: Cardiopulmonary Exercise Test

Detailed Description

Chemotherapy is widely used to treat a variety of cancers, and is associated with significant complications and even death. The established method for assessing patient fitness is by developing a clinical assessment of patient fitness, and classifying this using a performance status tool. Pancreatic Cancer patients with poorer performance status have been shown to have lower median survival of just 4 months. There is also evidence that patients with poorer performance status have lower response rates to other chemotherapy, higher complication rates, shorter progression free and overall survival. In clinical practice patients with performance status 2 are often offered chemotherapy, even though there is little evidence of its benefit, as the numbers of patients included in clinical trials with PS 2 is low and benefits from chemotherapy appear to be more modest.

Cardiopulmonary exercise testing is a non-invasive test that allows quantification of fitness. It is an objective measure of function capacity/fitness. It has been used in patients due to undergo major surgical intervention, and has the ability to identify those patients who are at higher risk of complications and mortality. CPET has been shown to be superior to the ASA in predicting peri-operative risk. The ASA classification is similar to PS in that it is graded from 1-4, and is a bedside assessment.

Despite the ability of PS to predict outcome it is a fairly blunt tool. The WHO PS is the most commonly used and is graded from 0-4. The categories are broad, for example a WHO PS of 0 could refer to a marathon runner or an elderly patient who is normally relatively inactive. Differentiating between grades is subject to observer error. There is reasonably good agreement between clinicians when differentiating between WHO grade 0-2 and 3-4, however variability exists within these subsets.

More recently it has been noted that it is harder to clinically assess older patients, and there is concern that many fit older patients are not being offered appropriate treatment. This is the subject of a current Department of Health (DoH) equality initiative.

The investigators are interested in identifying whether (CPET) offers additional benefit over that of WHO PS in the assessment of patients fitness for palliative chemotherapy for pancreatic cancer, by identifying those patients who might survive longer and tolerate chemotherapy better, thus predicting their outcome. The CPET variables most commonly used in risk prediction models are the volume of oxygen taken up at the anaerobic threshold relative to body mass (maximal oxygen consumption,VO2 at anaerobic threshold (AT)), the Peak oxygen uptake achieved during the exercise test relative to body mass (VO2 peak) and the oxygen pulse (O2 pulse) which is a derivative value involving oxygen uptake and the heart rate.

The benefit of CPET will be determined by the following:

• Overall survival at 6 months
• Response Rate (Response Evaluation Criteria In Solid Tumors criteria (RECIST) version 1.1)
• 60 day all-cause mortality
• Grade 3 and above adverse events (CTCAE v4) related to chemotherapy
• Chemotherapy dose intensity (% of planned doses given)
• Progression free survival (RECIST criteria version 1.1)
• European Organisation for Research and Treatment of Cancer (EORTC) quality of Life questionnaires (QLQ): to assess quality of life of cancer patients (QLQC30 (version 3)) and participants with pancreatic cancer (QLQ-PAN26)and a health survey 36 questionnaire (RAND 36-item short form health survey 1.0).
• Overall survival

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Simon A Winn, BSc; Phone Number: 0151 7055264; Email: simon.winn@liv.ac.uk
• Study Contact Backup: Name: Chloe Smith, BSc; Phone Number: 0151 795 5293; Email: chloenyc@liverpool.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

100 patients from the UK who have Pancreatic cancer and are due to commence palliative chemotherapy

Description

Inclusion Criteria:

• Histologically proven pancreatic cancer
• Due to commence palliative chemotherapy (including as part of a Clinical Trial of an Investigational Medicinal Product (CTIMP)).
• Able to undertake CPET
• Expected life expectancy >3 months
• Age 18+

Exclusion Criteria:

• Haemoglobin <10g/L

Absolute contraindications for cardiopulmonary exercise testing:

• Acute myocardial infarction (3-5 days)
• Unstable angina
• Uncontrolled arrhythmias causing symptoms or hemodynamic comprise
• Syncope
• Active endocarditis
• Acute myocarditis or pericarditis
• Symptomatic severe aortic stenosis
• Uncontrolled heart failure
• Acute pulmonary embolus or pulmonary infarction
• Thrombosis of lower extremities
• Suspected dissecting aneurysm
• Uncontrolled asthma
• Pulmonary edema
• Room air desaturation at rest ≤85%
• Respiratory failure
• Acute noncardiopulmonary disorder that may aggravated by exercise (i.e. renal failure, thyrotoxicosis)
• Mental impairment leading to inability to cooperate

Relative contraindications for cardiopulmonary exercise testing:

• Left main coronary stenosis or its equivalent
• Moderate stenotic valvular heart disease
• Severe untreated arterial hypertension at rest (>200mm Hg systolic, > 120mm Hg diastolic)
• Tachyarrhythmias or bradyarrhythmias
• High-degree atrioventricular block
• Hypertrophic cardiomyopathy
• Significant pulmonary hypertension
• Advanced or complicated pregnancy
• Orthopaedic impairment that compromises

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cardiopulmonary Exercise Test; A cardiopulmonary exercise bike test will be administered prior to palliative chemotherapy treatment.	Device: Cardiopulmonary Exercise Test; Cardiopulmonary Exercise Test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at 6 months (followed up for 12mths)	AUROC (Area under Receiver Operating Characteristic) for WHO (0-4) and WHO + CPET. A logistic regression model will be constructed, one with WHO PS and VO2 at AT (ml/kg/min).	6 months
Survival at 6 months (followed up for 12mths)	AUROC for WHO and WHO + CPET: A logistic regression model will be constructed with WHO PS and VO2 max (ml/kg/min).	6 months
Survival at 6 months (followed up for 12mths)	AUROC for WHO and WHO + CPET: A logistic regression model will be constructed with WHO PS and O2AT.	6 months
Survival at 6 months (followed up for 12mths)	The WHO+CPET classifier with the highest AUROC will then be compared with the AUROC for WHO alone.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-event endpoints	The Kaplan-Meier method will be used to estimate survival curves.	6 months

Collaborators and Investigators

• Sponsor: The Clatterbridge Cancer Centre NHS Foundation Trust
• Collaborators: University of Liverpool Cancer Research Centre
• Investigators: Principal Investigator: Daniel Palmer, Professor, Clatterbridge

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 12, 2017

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Cardiopulmonary Exercise Testing
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: RDD534

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No