IMMUNO-FIT Observational Study

NCT07354971 | Recruiting DMC

• 3 other identifiers: RHM CAN190525/SC/0293356874
• Study Type: observational
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

This observational study will investigate how immunotherapy affects physical fitness, quality of life, and treatment tolerance in adults with solid cancers. Immunotherapy can cause a range of side effects that impact daily functioning and may lead to treatment delays or early discontinuation. Physical fitness may influence how well patients cope with treatment, yet little is known about how fitness changes during immunotherapy or whether baseline fitness is linked to outcomes. Participants will complete fitness testing using cardiopulmonary exercise testing (CPET) and quality-of-life questionnaires before starting immunotherapy and again 12 weeks later. Blood samples will also be taken, and long-term outcomes including survival, disease progression, and quality of life will be followed for up to 24 months. All cancer treatment will remain standard of care. A small number of participants will be invited to take part in an optional research biopsy at week 12 to explore how physical fitness relates to changes in the tumour's immune environment. The study will help researchers understand natural changes in fitness during immunotherapy, identify whether baseline fitness is associated with treatment tolerance or outcomes, and generate information needed to design future trials testing exercise-based interventions during immunotherapy.

Conditions

Neoplasms; Immunotherapy; Physical Fitness; Quality of Life; Drug-Related Side Effects and Adverse Reactions

Keywords

Immunotherapy; Immune Checkpoint Inhibitors; Physical Fitness; Cardiopulmonary Exercise Testing; Quality of Life; Immune-Related Adverse Events; Cancer; Exercise Physiology; Tumour Microenvironment; PD-1; PD-L1; CTLA-4; Observational Study

Outcome Measures

Primary Outcomes (1)

• Change in Oxygen Uptake at Anaerobic Threshold (VO₂ at AT)

  Change in oxygen uptake at the anaerobic threshold measured using cardiopulmonary exercise testing (CPET). VO₂ at AT will be reported in millilitres per kilogram per minute (mL·kg-¹·min-¹).

  Baseline and Week 12

Secondary Outcomes (18)

• Change in peak oxygen uptake (VO₂peak)

  Baseline and Week 12

• Change in peak power output

  Baseline and 12 weeks

• Change in ventilatory efficiency (VE/VCO₂ slope)

  Baseline and week 12

• Cumulative Incidence of Immune-Related Adverse Events

  Baseline (start of immunotherapy) through Month 24

• Treatment-Related Adverse Events Leading to Discontinuation

  Baseline through Month 24

Other Outcomes (11)

• Overall survival

  Baseline (start of immunotherapy) through 24 months of follow-up

• Disease-free survival

  Baseline (start of immunotherapy) through 24 months of follow-up

• Event-free survival

  Baseline (start of immunotherapy) through 24 months of follow-up

Interventions

Observational Study - No Study Intervention OTHER

This is an observational study with no study-assigned interventions. All participants receive standard-of-care immunotherapy as prescribed by their treating oncologist. Immunotherapy may include anti-PD-1, anti-PD-L1, anti-CTLA-4 agents, or approved combination regimens. All doses, schedules, treatment modifications, delays, and discontinuations follow routine clinical practice and manufacturer guidance. Treatment decisions are made independently of the study. The study observes and records treatment administration, effects on fitness and quality of life, adverse events, and clinical outcomes without influencing clinical care.

Also known as: Standard of Care Immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults aged ≥18 years with histologically confirmed solid malignancies receiving immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or anti-CTLA-4) at University Hospital Southampton. Recruitment includes patients treated in the adjuvant setting with single-agent therapy after definitive local treatment, and patients in the metastatic or palliative setting receiving single- or dual-agent immunotherapy for advanced disease. The study uses a tumour-agnostic approach and includes any solid tumour for which immunotherapy is indicated. Examples include gastrointestinal, thoracic, skin, genitourinary, gynaecological, head and neck, breast, and other solid cancers treated with checkpoint inhibitors. Participants must have ECOG Performance Status 0-2 and be able to safely undertake cardiopulmonary exercise testing.

You may qualify if:

• Age ≥18 years
• Histologically confirmed solid malignancy
• Receiving immune checkpoint inhibitors in one of the following settings:
• Adjuvant: Single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4
• Metastatic/Palliative: Single-agent or dual-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4
• ECOG Performance Status 0-2
• Able to perform cardiopulmonary exercise testing
• Able to provide written informed consent
• Willing and able to comply with study procedures and follow-up schedule

You may not qualify if:

• Age \<18 years
• Prior systemic anti-cancer immunotherapy for unresectable or metastatic disease, EXCEPT:
• Prior adjuvant or neoadjuvant immunotherapy if all treatment-related adverse events have returned to baseline or stabilized
• Prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy with at least 6 months since last dose and date of disease recurrence
• Absolute contraindications to cardiopulmonary exercise testing:
• Acute myocardial infarction within 6 weeks
• Unstable angina
• Uncontrolled cardiac arrhythmias causing symptoms or hemodynamic compromise
• Active endocarditis
• Symptomatic severe aortic stenosis
• Uncontrolled heart failure
• Acute pulmonary embolism or pulmonary infarction
• Acute myocarditis or pericarditis
• Suspected or known dissecting aneurysm
• Acute systemic infection

Sponsors & Collaborators

• University Hospital Southampton NHS Foundation Trust: lead
• University of Southampton: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

RECRUITING

Related Publications (12)

• Kurz E, Hirsch CA, Dalton T, Shadaloey SA, Khodadadi-Jamayran A, Miller G, Pareek S, Rajaei H, Mohindroo C, Baydogan S, Ngo-Huang A, Parker N, Katz MHG, Petzel M, Vucic E, McAllister F, Schadler K, Winograd R, Bar-Sagi D. Exercise-induced engagement of the IL-15/IL-15Ralpha axis promotes anti-tumor immunity in pancreatic cancer. Cancer Cell. 2022 Jul 11;40(7):720-737.e5. doi: 10.1016/j.ccell.2022.05.006. Epub 2022 Jun 2.

  PMID: 35660135 BACKGROUND

• Wennerberg E, Lhuillier C, Rybstein MD, Dannenberg K, Rudqvist NP, Koelwyn GJ, Jones LW, Demaria S. Exercise reduces immune suppression and breast cancer progression in a preclinical model. Oncotarget. 2020 Jan 28;11(4):452-461. doi: 10.18632/oncotarget.27464. eCollection 2020 Jan 28.

  PMID: 32064049 BACKGROUND

• Maleki Vareki S. High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors. J Immunother Cancer. 2018 Dec 27;6(1):157. doi: 10.1186/s40425-018-0479-7.

  PMID: 30587233 BACKGROUND

• Kong X, Chen L, Su Z, Sullivan RJ, Blum SM, Qi Z, Liu Y, Huo Y, Fang Y, Zhang L, Gao J, Wang J. Toxicities associated with immune checkpoint inhibitors: a systematic study. Int J Surg. 2023 Jun 1;109(6):1753-1768. doi: 10.1097/JS9.0000000000000368.

  PMID: 37132038 BACKGROUND

• Kennedy LB, Salama AKS. A review of cancer immunotherapy toxicity. CA Cancer J Clin. 2020 Mar;70(2):86-104. doi: 10.3322/caac.21596. Epub 2020 Jan 16.

  PMID: 31944278 BACKGROUND

• McIsaac DI, Gill M, Boland L, Hutton B, Branje K, Shaw J, Grudzinski AL, Barone N, Gillis C; Prehabilitation Knowledge Network. Prehabilitation in adult patients undergoing surgery: an umbrella review of systematic reviews. Br J Anaesth. 2022 Feb;128(2):244-257. doi: 10.1016/j.bja.2021.11.014. Epub 2021 Dec 16.

  PMID: 34922735 BACKGROUND

• West MA, Baker WC, Rahman S, Munro A, Jack S, Grocott MP, Underwood TJ, Levett DZ; Fit-4-Surgery Consortium. Cardiopulmonary exercise testing has greater prognostic value than sarcopenia in oesophago-gastric cancer patients undergoing neoadjuvant therapy and surgical resection. J Surg Oncol. 2021 Dec;124(8):1306-1316. doi: 10.1002/jso.26652. Epub 2021 Aug 31.

  PMID: 34463378 BACKGROUND

• Loughney LA, West MA, Kemp GJ, Grocott MP, Jack S. Exercise interventions for people undergoing multimodal cancer treatment that includes surgery. Cochrane Database Syst Rev. 2018 Dec 11;12(12):CD012280. doi: 10.1002/14651858.CD012280.pub2.

  PMID: 30536366 BACKGROUND

• West MA, Loughney L, Barben CP, Sripadam R, Kemp GJ, Grocott MP, Jack S. The effects of neoadjuvant chemoradiotherapy on physical fitness and morbidity in rectal cancer surgery patients. Eur J Surg Oncol. 2014 Nov;40(11):1421-8. doi: 10.1016/j.ejso.2014.03.021. Epub 2014 Apr 12.

  PMID: 24784775 BACKGROUND

• Loughney L, West MA, Moyses H, Bates A, Kemp GJ, Hawkins L, Varkonyi-Sepp J, Burke S, Barben CP, Calverley PM, Cox T, Palmer DH, Mythen MG, Grocott MPW, Jack S; Fit4Surgery group. The effects of neoadjuvant chemoradiotherapy and an in-hospital exercise training programme on physical fitness and quality of life in locally advanced rectal cancer patients: a randomised controlled trial (The EMPOWER Trial). Perioper Med (Lond). 2021 Jun 22;10(1):23. doi: 10.1186/s13741-021-00190-8. Erratum In: Perioper Med (Lond). 2025 Dec 4;14(1):138. doi: 10.1186/s13741-025-00611-y.

  PMID: 34154675 BACKGROUND

• Steffens D, Ismail H, Denehy L, Beckenkamp PR, Solomon M, Koh C, Bartyn J, Pillinger N. Preoperative Cardiopulmonary Exercise Test Associated with Postoperative Outcomes in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analyses. Ann Surg Oncol. 2021 Nov;28(12):7120-7146. doi: 10.1245/s10434-021-10251-3. Epub 2021 Jun 8.

  PMID: 34101066 BACKGROUND

• Hapuarachi B, Danson S, Wadsley J, Muthana M. Exercise to transform tumours from cold to hot and improve immunotherapy responsiveness. Front Immunol. 2023 Dec 12;14:1335256. doi: 10.3389/fimmu.2023.1335256. eCollection 2023.

  PMID: 38149260 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples (plasma, serum, PBMCs) and tumour tissue (from optional research biopsies in mechanistic sub-study, n≤10) will be retained for 10 years in an HTA-licensed biobank for potential future research with appropriate ethical approval.

MeSH Terms

Conditions

Neoplasms; Drug-Related Side Effects and Adverse Reactions; Diabetes Mellitus, Insulin-Dependent, 12

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders

Study Officials

• Kashuf Khan, MBBS, MRCS

  University of Southampton

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kashuf Khan, MBBS, MRCS

CONTACT

+442381204308; k.a.khan@soton.ac.uk

Malcolm West, MD, PhD, FEBS, FRCS,

CONTACT

m.west@soton.ac.uk

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 21, 2026
• Study Start: March 26, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

GB (1)