Clinical trial NCT03626610: Prehabilitation of Patients With oEsophageal Malignancy Undergoing Peri-operative Treatment
Official title: 'Pre-EMPT' - An Interventional Study to Assess the Effects of Pre-emptive Exercise , or 'Prehabilitation', in Patients Undergoing Peri-operative Treatment for Adenocarcinoma of the Oesophagus and Gastro-oesophageal Junction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Oesophageal Adenocarcinoma
Chemotherapy Effect
Surgery
Keywords: Prehabilitation
Exercise
Cancer
Neo-adjuvant chemotherapy
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
First posted: 2018-08-13
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort-controlled
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 'Pre-EMPT' - A cohort-controlled, interventional study to assess the effects of a pre-emptive exercise programme, or 'prehabilitation', in patients undergoing peri-operative chemotherapy for adenocarcinoma of the lower oesophagus and gastro-oesophageal junction.

Detailed description: Oesophageal cancer has the fastest rising incidence of any solid tumour in the western world with the UK, and London, having particularly high rates of the disease.

Those patients being considered for "cure" will benefit from pre-operative/neo-adjuvant chemotherapy (NAC), which is known to have a deleterious effect on fitness and is associated with increased post-operative morbidity. Post-operative morbidity is also associated with reduced survival. Reduction in fitness is compounded by major surgery and significantly reduces the numbers of patients who commence or complete the standard treatment of post-operative chemotherapy to around 40%.

Chemotherapy and surgery for oesophageal cancer both represent significant physiological insults that may have detrimental effects on physical activity and outcomes after surgery. Cardiopulmonary exercise (CPEX) testing has been effectively used in numerous tumour groups to predict outcome after surgery, although its role in oesophageal cancer patients remains uncertain owing to conflicting data from institutional series. Advanced exercise programmes, sometimes termed 'prehabilitation', directed by experienced multidisciplinary teams are increasingly being used to mitigate the secondary effects of cancer treatment.

'Prehabilitation' has been shown to reduce postoperative morbidity and mortality in thoracic patients undergoing elective high-risk surgery. In addition, results of studies examining physical exercise and cancer recurrence/survival which effect immune system function in cancer survivors suggest that physical exercise training may improve a number of immune system parameters that may be important in cancer defence.

The investigators believe that optimising patient fitness through a structured and expert-devised exercise programme of 'prehabilitation' during neo-adjuvant chemotherapy and prior to surgery will mitigate the effects of chemotherapy and improve patient outcomes after surgery.

The investigators intend to assess the feasibility of a 'prehabilitation' programme and quantify the resultant effects primarily using CPEX testing. In addition, changes in hospital 'length of stay' will be documented with a number of additional parameters.

Eligibility criteria: Inclusion Criteria:

1. Participants must be diagnosed with operable oesophageal and gastro-oesophageal adenocarcinoma and scheduled to undergo standard neo-adjuvant chemotherapy and oesophago-gastric surgery as recommended by the Multidisciplinary Meeting decision.
2. 18+
3. \</=79 (patients above this age may be included in studies after the feasibility study has been completed)
4. Participants must be able to understand and independently consent to participation in the study.
5. Participants must be able to understand and complete the questionnaires.
6. Participants must be willing to undergo all the standard assessments and interventions included in this study - CPEX testing, blood sampling, questionnaires and exercise intervention where appropriate.
7. Participants must be willing to wear the Fibit monitoring device and agree with its use
8. Participants must be ASA 1-3 and fit for surgical resection
9. Patients should have a Body Mass Index (BMI) equal to or above 18.5 with less than 10% self-reported unintentional weight loss at diagnosis.

Exclusion Criteria:

Participants will be excluded if they:

1. Are not considered medically fit for surgery at diagnosis, as decided by the Multidisciplinary team
2. Will undergo primary or palliative chemotherapy
3. Are recommended to have chemoradiotherapy
4. Are under 18 years old
5. Are over 79 years old
6. Are unable to undergo CPEX testing
7. Do not wish to take part in selected aspects of the study
8. Cannot or do not wish to attend the CHHP for assessment and/or advice on exercise
9. Cannot understand and give informed consent to the study
10. Cannot understand and complete the questionnaires
11. Do not wish to wear a Fitbit monitoring device
12. ASA 4+
13. Patients with BMI of less than 18.5 with self-reported unintentional weight loss of 10% or more at diagnosis.

Primary outcomes:
measure: Cardiopulmonary fitness
timeFrame: Baseline to 5 months
Secondary outcomes:
measure: Post-operative complications
timeFrame: Date of surgery to date of discharge, up to 45 days post-surgery
measure: Post-operative length of hospital stay
timeFrame: Date of surgery to date of discharge, up to 45 days post-surgery
measure: Lean body mass
timeFrame: Baseline to 5 months
measure: Daily activity levels
timeFrame: Baseline to 5 months
measure: Sleep quality assessment
timeFrame: Baseline to 5 months
measure: Change in Health-related Quality of Life: Oesophageal cancer-specific questionnaire
timeFrame: Baseline to 12 months post-surgery
measure: Change in Health-related Quality of Life: Cancer questionniare
timeFrame: Baseline to 12 months post-surgery
measure: Change in Well-being
timeFrame: Baseline to 12 months post-surgery
measure: Disease recurrence
timeFrame: Date of surgery to date of recurrence, up to 12 months post-surgery
measure: Post-operative mortality
timeFrame: Date of surgery to date of death, up to 12 months post-surgery
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: St Thomas' Hospital
Study officials:
affiliation: Consultant Surgeon
name: Andrew Davies, MBChBMDFRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zylstra J, Whyte GP, Beckmann K, Pate J, Santaolalla A, Gervais-Andre L, Russell B, Maisey N, Waters J, Tham G, Lagergren J, Green M, Kelly M, Baker C, Van Hemelrijck M, Goh V, Gossage J, Browning M, Davies A. Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial. Br J Sports Med. 2022 Apr;56(7):402-409. doi: 10.1136/bjsports-2021-104243. Epub 2022 Feb 1.