The Immuno-FIT Observational Study: A Phase II Window Observational Study Investigating the Effects of Immunotherapy on Cardiopulmonary Fitness, Quality of Life, and Treatment Outcomes in Patients With Advanced Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 67
- 试验地点
- 1
- 主要终点
- Change in Oxygen Uptake at Anaerobic Threshold (VO₂ at AT)
研究概览
简要总结
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.
详细描述
Physical fitness is a strong prognostic marker in cancer. Reduced cardiorespiratory fitness, measured objectively using cardiopulmonary exercise testing (CPET), is associated with higher perioperative risk, increased treatment-related complications, and poorer quality of life. Previous work from the study team and others has shown that chemotherapy and chemoradiotherapy for oesophageal and rectal cancer lead to significant declines in CPET-derived fitness, and that prescribed exercise prehabilitation can attenuate or reverse these declines and improve clinical outcomes.
Immune checkpoint inhibitors have become standard of care for a growing range of solid tumours in both adjuvant and metastatic settings. Immunotherapy is associated with distinct patterns of toxicity, including immune-related adverse events and cumulative treatment-related side effects that can impair day-to-day functioning, result in treatment delays, or lead to early discontinuation. However, the impact of immunotherapy on objectively measured physical fitness, and the extent to which baseline fitness and changes in fitness relate to toxicity, quality of life, and long-term outcomes, remains poorly defined.
Emerging evidence suggests complex interactions between physical fitness, immune function, and tumour biology. Exercise can influence systemic immunity and the tumour microenvironment, including increased infiltration of cytotoxic T cells and modulation of myeloid populations. These effects may help convert immunologically "cold" tumours with limited immune cell infiltration into "hot" tumours that are more responsive to immunotherapy. Understanding how baseline fitness and natural changes in fitness during immunotherapy relate to treatment tolerance and tumour-immune characteristics is therefore an important step towards rationally developing exercise-based interventions as potential adjuncts to immunotherapy.
This Phase II window observational study is a prospective, single-centre cohort study with an embedded mechanistic sub-study. It will enrol adults with histologically confirmed solid malignancies who are starting standard-of-care immune checkpoint inhibitor therapy at University Hospital Southampton NHS Foundation Trust. The trial adopts a tumour-agnostic approach, stratifying participants by treatment setting (adjuvant vs metastatic/palliative) and immunotherapy regimen (single-agent vs dual-agent checkpoint inhibition). This reflects real-world practice and allows evaluation of how treatment context and intensity influence changes in fitness and attrition.
For the observational cohort, participants will undergo baseline assessments within approximately two weeks prior to starting immunotherapy. These include CPET on a cycle ergometer to determine oxygen uptake at the anaerobic threshold (VO₂ at AT; primary outcome) and other CPET parameters, a panel of validated questionnaires assessing cancer-specific and generic quality of life, psychological distress, fatigue, social support and functional impact, grip strength, frailty assessment, targeted blood sampling (including nutritional markers, immune and metabolic biomarkers, and redox-related analytes), and review of standard-of-care imaging. Baseline medical history, comorbidities, and performance status will also be recorded.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Inability to perform cardiopulmonary exercise testing (e.g., severe lower limb dysfunction, severe peripheral vascular disease)
- •Inability to provide informed consent
- •Currently enrolled in another interventional clinical trial that would confound study outcomes
- •ADDITIONAL EXCLUSION CRITERIA FOR RESEARCH BIOPSY SUB-STUDY:
- •Severe cardiopulmonary disease precluding safe sedation (for endoscopic biopsies)
- •Suspected bowel obstruction or perforation (for gastrointestinal biopsies)
- •Uncorrectable severe coagulopathy (INR >1.5, platelet count <50,000/µL)
- •Severe portal hypertension with high-risk varices (for upper endoscopy)
- •Lesion inaccessible for safe biopsy as determined by a performing clinician
结局指标
主要结局
Change in Oxygen Uptake at Anaerobic Threshold (VO₂ at AT)
时间窗: Baseline and Week 12
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).
次要结局
- 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)
- Change in cancer-specific quality of life(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in general health status(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in psychological distress(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in anxiety and depression symptoms(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in fatigue severity(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in perceived social support(Baseline, Week 12, Month 6, Month 12, and Month 24)
- Change in functional impairment(Baseline, Week 12, Month 6, Month 12, Month 24)
- Change in functional capacity(Baseline, Week 12, Month 6, Month 12, Month 24)
- Change in frailty status(Baseline, Week 12, Month 6, Month 12, Month 24)
- Recruitment feasibility(During recruitment period - 12 months)
- Adherence to research assessments(Baseline and Week 12)
- Feasibility of Optional Research Biopsy(Week 12)
- Biopsy-related complications(Week 12)