Effect of Pre-operative Exercise Training on Cardiorespiratory Fitness in Patients With Locally Advanced Non-small Cell Lung Cancer Undergoing Induction Chemo-immunotherapy Followed by Surgery - a Randomized Controlled Study (PREHAB)

March 16, 2026 updated by: Hôpital du Valais

The PREHAB study focuses on patients with locally advanced non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy and/or immunotherapy prior to surgical resection. These systemic treatments frequently impair patients' physiological reserve, reduce physical fitness, and may occasionally lead to cancellation of surgery. Surgery itself carries a substantial risk of cardiorespiratory complications and long-term functional decline.

The primary objective of this study is to determine whether a supervised exercise program, initiated concomitantly with systemic therapy and continued until surgery, can improve cardiorespiratory fitness, surgical tolerance, and postoperative outcomes.

A total of 74 patients will be randomly assigned to one of two groups: an "intervention" group participating in three weekly sessions of supervised endurance and resistance training for 12 to 16 weeks under the guidance of a physiotherapist, and a "control" group receiving usual care without a structured exercise program.

The primary endpoint will be peak oxygen uptake (VO₂peak). Secondary outcomes will include postoperative complication rates, length of hospital stay, pulmonary function, skeletal muscle mass, and quality of life.

Intervention-related risks, primarily falls or overexertion, will be mitigated through professional supervision. This multicenter study, with recruitment scheduled to begin in 2026, is expected to provide robust evidence regarding the effectiveness of targeted exercise training in improving preoperative fitness and postoperative recovery in patients with locally advanced NSCLC.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The PREHAB study is a prospective, multicenter, randomized controlled trial designed to evaluate the efficacy of a structured, supervised prehabilitation program in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy and/or immunotherapy prior to surgical resection.

Patients with stage III NSCLC increasingly receive multimodal treatment strategies combining systemic therapy followed by surgery. While neoadjuvant chemotherapy and immunotherapy have improved oncologic outcomes, these treatments frequently induce treatment-related deconditioning, sarcopenia, fatigue, and reduced cardiopulmonary reserve. Consequently, a subset of patients experiences functional decline significant enough to compromise surgical eligibility. Moreover, thoracic surgery itself is associated with substantial postoperative morbidity, particularly cardiorespiratory complications, and long-term impairment in physical performance.

The PREHAB trial is based on the hypothesis that early, structured, and supervised exercise training initiated concomitantly with systemic therapy and continued until surgery can mitigate treatment-induced physiological deterioration, preserve or enhance cardiorespiratory fitness, and ultimately improve perioperative and postoperative outcomes.

A total of 74 patients will be randomized in a 1:1 ratio to either:

  • Intervention group: participation in a 12-16 week supervised exercise program consisting of three weekly sessions combining endurance and resistance training, delivered by trained physiotherapists.
  • Control group: standard oncologic care without a structured exercise intervention.

The primary endpoint is change in peak oxygen uptake (VO₂peak), measured by cardiopulmonary exercise testing, as an objective marker of cardiorespiratory fitness and surgical resilience.

Secondary endpoints include:

  • Postoperative complication rates
  • Length of hospital stay
  • Pulmonary function parameters
  • Skeletal muscle mass
  • Health-related quality of life

Safety considerations focus primarily on the risk of falls and overexertion, both minimized through professional supervision and individualized exercise prescription.

By targeting the vulnerable neoadjuvant window - when patients are exposed to systemic therapy but have not yet undergone surgery - PREHAB aims to redefine perioperative optimization in locally advanced NSCLC. If positive, this trial could provide high-level evidence supporting the integration of structured exercise prehabilitation into standard multimodal lung cancer care pathways.

Study Type

Interventional

Enrollment (Estimated)

74

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 Locations

  • Switzerland
    • Canton of Geneva
      • Geneva, Canton of Geneva, Switzerland, 1205
        • Hôpitaux Universitaires de Genève
        • Contact:
        • Principal Investigator:
          • Benoît Bédat, PD
    • Canton of Vaud
      • Lausanne, Canton of Vaud, Switzerland, 1005
        • Centre Hospitalier Universitaire Vaudois
        • Contact:
        • Principal Investigator:
          • Michel Gonzalez, Professor
    • Valais
      • Sion, Valais, Switzerland, 1951
        • Hopital de Sion
        • Contact:
        • Principal Investigator:
          • Céline Forster, MD

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18 years.
  • Confirmed diagnosis of stage IIB, IIIA, IIIB or oligo-metastatic stage IV NSCLC.
  • Planned induction therapy with either chemotherapy, immunotherapy or a combination of immuno-chemotherapy followed by an anatomical pulmonary resection.
  • Absence of musculoskeletal conditions preventing safe physical exercise.
  • Absence of any history of uncontrolled or unstable cardiac disease.
  • Agreement to participate in the study by signing the study specific informed consent form.

Exclusion Criteria:

  • Pregnancy (confirmed by a test if applicable).
  • Induction therapy already initiated.
  • Inability to walk independently.
  • Lack of decision-making capacity.
  • Oxygen-dependency before the initiation of the induction protocol.
  • No capacity for discernment.
  • Does not speak French.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Intervention group: participation in a 12-16 week supervised exercise program consisting of three weekly sessions combining endurance and resistance training, delivered by trained physiotherapists.
Procedure: Preoperative Exercise Training

The intervention consists of a structured, supervised pre-operative exercise training program initiated concomitantly with induction chemo- and/or immunotherapy and continued until 24-72 hours prior to surgery. The program is delivered in an outpatient setting and supervised by trained physiotherapists following a standardized protocol across study sites.

Participants randomized to the intervention group will complete three sessions per week, each lasting 45-60 minutes, for a total duration of 12 to 16 weeks depending on the length of induction therapy. Each session combines aerobic and resistance training components. Aerobic exercise is performed on a cycle ergometer at an initial intensity of approximately 60% of baseline VO₂peak, with progressive increases in duration and intensity aiming for 30-40 minutes at a Borg perceived exertion score of 4-6. Resistance training targets major upper and lower muscle groups using functional exercises.
No Intervention: Control
Control group: standard oncologic care without a structured exercise intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in peak oxygen uptake (VO₂peak) from baseline to pre-surgery
Time Frame: From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
The primary endpoint is peak oxygen uptake (VO₂peak), measured by standardized cardiopulmonary exercise testing (CPET). VO₂peak reflects the integrative capacity of the cardiovascular, pulmonary, and muscular systems during maximal exertion and is a validated indicator of surgical fitness and perioperative risk. VO₂peak will be assessed at baseline (before induction therapy) and repeated 24-72 hours prior to surgery. The primary analysis will compare pre-surgery VO₂peak between groups using ANCOVA adjusted for baseline VO₂peak.
From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ventilatory efficiency (VE/VCO₂ slope) from baseline to pre-surgery
Time Frame: From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
VE/VCO₂ slope measured during CPET as an index of ventilatory efficiency and ventilation-perfusion matching. Elevated values are associated with increased perioperative risk. The outcome is the between-group difference at pre-surgery adjusted for baseline value.
From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Change in 6-minute walk distance from baseline to pre-surgery
Time Frame: From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Distance walked during the standardized 6-minute walk test (6MWT) performed indoors on a 30-meter corridor according to established guidelines. The outcome is the between-group difference in walking distance at pre-surgery adjusted for baseline.
From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Rate of 30-day postoperative cardiopulmonary complications
Time Frame: From surgery to 30 days postoperatively.
Proportion of patients experiencing at least one predefined cardiopulmonary complication within 30 days after surgery, including atrial fibrillation, pneumonia, prolonged air leak, pulmonary embolism, ARDS, pneumothorax, or myocardial infarction. Between-group comparison.
From surgery to 30 days postoperatively.
Length of postoperative hospital stay
Time Frame: From surgery until hospital discharge.
Number of days from the date of surgery to hospital discharge. Comparison of mean length of stay between intervention and control groups.
From surgery until hospital discharge.
Change in health-related quality of life (EORTC QLQ-C30 global score)
Time Frame: From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Health-related quality of life assessed using the EORTC QLQ-C30 questionnaire (version 3.0). The primary QoL endpoint is the global health status/quality of life score. Between-group comparison of change from baseline to pre-surgery.
From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Change in skeletal muscle cross-sectional area on CT imaging
Time Frame: From baseline to 4-6 weeks prior to surgery at approximately 12 weeks.
Skeletal muscle cross-sectional area and radiodensity measured on CT scans at the L3 vertebral level. Change from baseline to pre-surgery compared between groups as an index of sarcopenia and muscle quality.
From baseline to 4-6 weeks prior to surgery at approximately 12 weeks.
Change in pulmonary function (FEV1 and DLCO) from baseline to pre-surgery
Time Frame: From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.
Forced expiratory volume in 1 second (FEV1) and diffusing capacity for carbon monoxide (DLCO) measured using standardized pulmonary function testing. Between-group comparison of change from baseline to pre-surgery.
From baseline to 24-72 hours prior to surgery at approximately 12-16 weeks.

Collaborators and Investigators

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

Sponsor

Hôpital du Valais

Collaborators

University Hospital, Geneva
Centre Hospitalier Universitaire Vaudois

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 (Estimated)

April 1, 2026

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

April 1, 2029

Study Registration Dates

First Submitted

March 4, 2026

First Submitted That Met QC Criteria

March 16, 2026

First Posted (Actual)

March 18, 2026

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Preoperative exercise training

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) underlying the results reported in the publication of the primary and secondary outcomes will be shared. This will include de-identified individual-level data for baseline characteristics, group allocation, primary outcome data (VO₂peak at baseline and pre-surgery), secondary outcome measures (VE/VCO₂ slope, 6-minute walk distance, postoperative complications, length of stay, pulmonary function, skeletal muscle mass, and quality of life scores), and adherence data.

All shared data will be fully de-identified in accordance with applicable data protection regulations. The study protocol, statistical analysis plan, and data dictionary will also be made available.

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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