Will a Pre-therapy Exercise Intervention Improve the Outcomes of Patients With Advanced Oesophageal Cancer? (OPTIMUS)

January 29, 2026 updated by: Adam Frampton, University of Surrey

Optimising Prehabilitation Exercise to Enhance Tumour Outcomes in Advanced Oesophageal Cancer

Background

Regular exercise can significantly improve physical and mental health during cancer treatment and reduce the time needed in the hospital. Animal studies suggest that exercise training can also reduce the number of cancer cells. For example, exercise training in mice produces more immune cells in the tumour. These immune cells in the tumour contribute to the destruction and reduction of the size of the tumour and are a vital component of effective immunotherapy (cancer treatment that helps the immune system fight cancer).

In humans, exercise training and the immune response in tumours are less understood. Only 1 study has investigated the effect of a single exercise session before surgical removal of the prostate in prostate cancer patients. As the benefits of exercise are gained from weeks/months of exercise, no effect on the immune cells in the tumours were found.

The investigators have carried out a previous study looking at how exercise affects fitness before major surgery. After this they used state-of-the-art methods to detect and visualise immune cells within the tumour. Compared with the patients who did not exercise, the exercise group had significantly more immune cells in their tumours, consisting of a group of cells that are important for killing cancerous cells called CD8+ T cells. CD8+ T cells in tumours are associated with improved survival outcomes.

Importantly, they found a link between changes in fitness and the amount of these cells in the tumour. This suggests that if there is increase in fitness, there also an increase in the frequency of these cells in the tumour. Therefore, the investigators propose performing a clinical trial to find out the best level of exercise patients need to sustain before surgery to produce this improved immune response.

The trial will aim to understand how this happens and how the entry of immune cells into the tumour changes the environment around a tumour. The investigators consist of a team of exercise immunologists, tumour immunologists and clinicians working with the Human Performance Institute at the University of Surrey in collaboration with the Royal Surrey NHS Trust.

How it will be done

The investigators will assess immune cell response in blood samples obtained from oesophageal cancer patients before, during and after a high or low intensity exercise programme. Following the exercise programme, tumour tissue removed at surgery from these patients will be used to investigate the the presence and quantity of these immune cells.

Potential impact

A better understanding of this is important, as current anti-cancer immune-based therapeutics work best when there is a an immune response within the patient's tumour. Generating evidence that exercise can improve the immune response against the tumour in patients with oesophageal cancer would provide significant justification for introducing "personalised" exercise programmes to improve treatment outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Oesophageal cancer is one of the most challenging cancers to treat, with low survival rates, even when people receive intensive treatments such as chemotherapy and surgery. New treatment strategies could therefore lead to significant benefits to patients.

One of the most promising new treatments is immunotherapy, which works by "releasing the brakes" on immune cells. Immunotherapy has transformed outcomes in some cancers, but its impact in oesophageal cancer has been modest so far. One important reason may be that many oesophageal tumours contain few active immune cells to begin with. Finding safe, practical ways to ''wake up'' the immune system and draw immune cells into the tumour could make existing treatments more effective.

Exercise is a simple, low-cost option that could help. Exercise programmes are already used before major surgery to improve fitness and help people cope better with treatment. Research in other cancers shows that exercise can increase the number and activity of key immune cells in the blood and, in some cases, inside tumours. Exercise also affects the gut microbiome. This is the community of bacteria and other microorganisms in our intestines, and the chemicals they produce. These microbial products can travel through the bloodstream and shape how the immune system behaves. However, it is still unclear yhow these changes work together in people with oesophageal cancer receiving chemotherapy.

In this study, people with oesophageal cancer who are due to receive chemotherapy before surgery will be invited to join a supervised exercise programme. All patients will exercise under the guidance of specialist staff while they are on chemotherapy. One group will follow a lower-intensity programme similar to current NHS prehabilitation. The other group will complete higher-intensity sessions, within safe limits. Comparing these two realistic options will allow us to test whether exercise intensity makes a difference.

The investigators will collect blood and stool samples at key time points before and during treatment. From blood, there will be an analysis of the changes in immune cells and proteins that signal how "switched on" the immune system is. From stool, the investigators will study the gut microbiome and the metabolites (small molecules) they produce. After surgery, the removed tumour will be examined under the microscope to see whether exercise is linked to differences in the number and type of immune cells inside the tumour. By bringing these measurements together, we hope to understand whether more intensive exercise leads to a more immune-active tumour, and how the change in immune cells alongside systemic signalling molecules are related to these states.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
    • Surrey
      • Guildford, Surrey, United Kingdom, GU2 7XH
        • Recruiting
        • University of Surrey
        • Contact:
        • Sub-Investigator:
          • Jamal Dirie, MD
        • Principal Investigator:
          • Adam Frampton, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults with resectable oesophageal adenocarcinoma who are planned for neoadjuvant chemotherapy followed by surgery

Exclusion Criteria:

  • Inability to carry out CPET or exercise due to underlying health conditions
  • pregnancy
  • <18 years old

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low intensity/Low amount (LAM) arm
Behavioral: Low intensity exercise
Participants undertake supervised cycling twice weekly. Each session comprises 5 min warm-up at 30% heart rate reserve (HRR), then 20 min continuous cycling starting at 40% HRR. After participants complete two supervised sessions/week at 40% HRR without adverse events, intensity increases by 5% HRR per session to a target of 60% HRR, which is maintained for the remainder of the pre-operative period (until surgery). After cycling, participants complete flexibility and resistance exercises targeting six major muscle groups (2 sets of 12 repetitions, rating of perceived exertion (RPE) 12-14), with load increased when RPE <12. Participants also complete a home programme three times weekly (60 min/session) focusing on resistance and core stability using appropriately weighted bands.
Experimental: moderate-vigorous-intensity/moderate-high-amount (MAM) arm
Behavioral: High intensity exercise
Exercise Group 2 (moderate-vigorous-intensity/moderate-high-amount (MAM)) is a progressive, individualised programme with two supervised aerobic sessions/week using harness-supported treadmill walking where possible, or cycle ergometry if needed. Each session begins with 5 min at 40% heart rate reserve (HRR). For ~2 weeks, participants complete 15 min of intervals (30 s at 80% HRR then 1 min at 50% HRR), followed by 5 min cool-down at 40% HRR. Training then progresses by increasing hard bouts to 1 min, building to 20 intervals, then targeting 90%/50% HRR with gradual increases in time spent at 90% HRR. After aerobic exercise, flexibility plus resistance (chest press, leg press, seated row) is performed for 2 sets to fatigue at rating of perceived exertion (RPE) 15-17, increasing load when 2x25 reps are achieved. Home aerobic exercise is prescribed for 60 min, 3x/week at ~60% HRR using heart-rate telemetry (home cycle provided if walking not feasible).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumour immune infiltration
Time Frame: From enrollment to the end of treatment at 16 weeks
Percentage increase of CD8 T Cells within the tumour
From enrollment to the end of treatment at 16 weeks
Improvement in cardiorespiratory function
Time Frame: From enrollment to the end of treatment at 16 weeks
Measured through VO2 peak
From enrollment to the end of treatment at 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in peripheral blood mononuclear cells (PBMC)
Time Frame: From enrollment to the end of treatment at 16 weeks
We will analyse longitudinal shifts in PBMC subsets and phenotypes.
From enrollment to the end of treatment at 16 weeks
Change in plasma cytokines
Time Frame: From enrollment to the end of treatment at 16 weeks
We will analyse longitudinal shifts in PBMC subsets and phenotypes.
From enrollment to the end of treatment at 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Surrey

Collaborators

World Cancer Research Fund International

Investigators

  • Principal Investigator: Adam Frampton, PhD, University of Surrey

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 26, 2024

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

October 30, 2028

Study Registration Dates

First Submitted

January 21, 2026

First Submitted That Met QC Criteria

January 21, 2026

First Posted (Actual)

January 29, 2026

Study Record Updates

Last Update Posted (Actual)

February 2, 2026

Last Update Submitted That Met QC Criteria

January 29, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 326527

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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