Exercise as a Tool to Improve Response to Immunotherapy in Non-small Cell Lung Cancer

NCT ID: NCT07267000

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-01
• Study Completion Date: 2029-05-01

Brief Summary

This project is about the effect of a 12-week training therapy intervention in patients suffering from non-small cell lung cancer. It has widely been accepted that exercise is preventive against certain types of cancer. Individuals following an active lifestyle have a significantly lower risk for several chronic diseases, including cancer, as compared to sedentary ones. However, evidence is still lacking for exercise as part of routine cancer treatment (as it has already been implemented routinely in patients with heart disease, for example). In this study, patients suffering from non-small cell lung cancer undergo either a 12-week training program consisting of moderate-intensity continuous exercise (MICE), or a 12-week program with high-intensity interval exercise. Both groups will be compared to a control group receiving standard exercise recommendations. The response to immunotherapy, measured by the radiologic therapy response, will be the main endpoint. Additionally, blood will be taken from the patients at different timepoints, and blood samples will be tested for immunologic changes. FACS analysis will be used to assess the properties of immune cells and potential changes upon the exercise regimen. Mitochondrial function will be assessed via the Seahorse machine, and mass spectrometry (lipidomics) will be used for the analysis of lipid profile changes.

Detailed Description

Lung cancer is the number one cause of cancer-related deaths worldwide. A few decades ago, the prognosis at lung cancer first diagnosis was generally poor with only a few months of median survival. New immunotherapy treatment regimens have markedly improved survival times - especially in certain histologic and molecular pathologic subtypes. The positive effect of exercise on the incidence of several cancer entities such as colorectal- or breast cancer, has been demonstrated previously. Physically active individuals are diagnosed with cancer significantly less often as compared to sedentary people. In oncologic follow-up care, a positive effect of exercise and training with an advantage in survival has also been proven, e.g. in breast cancer patients.

In addition, existing data shows a positive effect of exercise on the immune system: active individuals show a different pattern of proinflammatory markers in the blood serum, with every exercise session generating an immune-stimulatory effect which changes the immunologic serum profile also at rest. Thus, regular exercise has an anti-inflammatory long-term effect.

Hypothesis and Objectives: With our project we seek to demonstrate a possible benefit on immunotherapy response upon a medically guided training regimen.

Setting and Methods. To exactly define "exercise" in this setting, as a first step we will test two exercise types in healthy individuals. According to their individual exercise capacity as determined by spiroergometry, healthy subjects will either perform moderate-intensity continuous exercise (MICE), or a high-intensity interval training (HIIT). By means of venous blood sampling before and after training we shall determine the respective changes of serum immune markers through exercise. The same two training types will then be performed by lung cancer patients upon immunotherapy, with one patient group doing MICE-sessions, one group doing the HIIT and a third group who will receive general exercise recommendations. Response to therapy and inflammatory serum parameters will be compared between the groups. Exercising patients will be advised to train once a week under medical supervision, and to walk briskly for 30 minutes every day of the week in addition. Our hypothesis is, that exercise should be implemented as a complementary treatment strategy in every oncologic therapy setting, possibly improving not only physical health and wellbeing but also treatment response. In addition to improving the patients' quality of life by a better physical capacity and fitness, helping them in their everyday activities, we propose that the implementation of exercise programs in various oncologic settings in future may improve the patients' outcome.

Scientific Novelty. Standardization of exercise regimens in oncologic scenarios in the existing literature is generally poor. We carry out one of the few studies where the type, duration, timing and intensity of exercise in both exercise groups is clearly defined, comparing two different training types to sedentary control patients, respectively. Exercise needs to be seen as a drug, and like in any drug the optimum dose must be clearly outlined. Moreover, we will implement a priming exercise in our study, meaning that patients exercise close to the administration of immunotherapy, hypothesizing that this may further ameliorate therapy response.

Conditions

Non-Small Cell Lung Cancer; Exercise Training; Immunotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Continuous Exercise

Patients in this arm will undergo a 12-week training therapy regimen consisting of twice weekly supervised moderate-intensity continuous exercise (MICE) and home-based walking exercise for 30 minutes, five times a week, in addition.

Group Type: EXPERIMENTAL

Exercise

Intervention Type: BEHAVIORAL

1 study arm doing continuous type exercise will be compared to 1 study arm doing high-intensity interval exercise, over the course of 12 weeks, respectively. Both arms will be compared to sedentary control patients.

High Intensity Interval Exercise

Patients in this arm will undergo a 12-week training therapy regimen consisting of twice weekly supervised high-intensity interval exercise and home-based walking exercise for 30 minutes, five times a week, in addition.

Group Type: EXPERIMENTAL

Exercise

Intervention Type: BEHAVIORAL

1 study arm doing continuous type exercise will be compared to 1 study arm doing high-intensity interval exercise, over the course of 12 weeks, respectively. Both arms will be compared to sedentary control patients.

Controls

Patients in this arm will receive general recommendations on an active lifestyle, but will not take part in supervised training sessions and are not asked to do home-based exercise either.

Group Type: ACTIVE_COMPARATOR

Control

Intervention Type: OTHER

For patients in the control group, general exercise recommendations (e.g. recommendations by the CDC suitable for all adult individuals) will be given, however, no training therapy intervention is done and no home-based walking exercise is required either.

Interventions

Exercise

1 study arm doing continuous type exercise will be compared to 1 study arm doing high-intensity interval exercise, over the course of 12 weeks, respectively. Both arms will be compared to sedentary control patients.

Intervention Type: BEHAVIORAL

Control

For patients in the control group, general exercise recommendations (e.g. recommendations by the CDC suitable for all adult individuals) will be given, however, no training therapy intervention is done and no home-based walking exercise is required either.

Intervention Type: OTHER

Other Intervention Names

Home-based walking exercise

Eligibility Criteria

Inclusion Criteria

-

Exclusion Criteria

• Kachexia (BMI<18.5)
• instable bone metastases
• orthopedic condition rendering the patient unable to ride a stationary bike
• any medical contraindication for exercise and training

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Graz

OTHER

Sponsor Role: collaborator

Austrian Science Fund (FWF)

OTHER

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medical University of Graz

Graz, , Austria

Countries

Austria

Central Contacts

Elisabeth Taucher, Dr. Dr.

Role: CONTACT

elisabeth.taucher@medunigraz.at

+436648438876

Peter Hofmann, Prof. Mag. Dr.

Role: CONTACT

+43 316 380 3903

Facility Contacts

Elisabeth Taucher, Dr. Dr.

Role: primary

elisabeth.taucher@medunigraz.at

+43 6648438876

Nikolaus Kneidinger, Prof. Dr.

Role: backup

nikolaus.kneidinger@medunigraz.at

+43 316 385 12183

References

Martin-Ruiz A, Fiuza-Luces C, Rincon-Castanedo C, Fernandez-Moreno D, Galvez BG, Martinez-Martinez E, Martin-Acosta P, Coronado MJ, Franco-Luzon L, Gonzalez-Murillo A, Ramirez M, Provencio M, Lucia A. Benefits of exercise and immunotherapy in a murine model of human non-small-cell lung carcinoma. Exerc Immunol Rev. 2020;26:100-115.

Reference Type: BACKGROUND

PMID: 32139351 (View on PubMed)

Ungvari Z, Fekete M, Varga P, Munkacsy G, Fekete JT, Lehoczki A, Buda A, Kiss C, Ungvari A, Gyorffy B. Exercise and survival benefit in cancer patients: evidence from a comprehensive meta-analysis. Geroscience. 2025 Jun;47(3):5235-5255. doi: 10.1007/s11357-025-01647-0. Epub 2025 Apr 12.

Reference Type: BACKGROUND

PMID: 40220151 (View on PubMed)

Winters-Stone KM, Neil SE, Campbell KL. Attention to principles of exercise training: a review of exercise studies for survivors of cancers other than breast. Br J Sports Med. 2014 Jun;48(12):987-95. doi: 10.1136/bjsports-2012-091732. Epub 2013 Jan 4.

Reference Type: BACKGROUND

PMID: 23293010 (View on PubMed)

Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019 Nov;51(11):2375-2390. doi: 10.1249/MSS.0000000000002116.

Reference Type: BACKGROUND

PMID: 31626055 (View on PubMed)

Rezende LFM, Sa TH, Markozannes G, Rey-Lopez JP, Lee IM, Tsilidis KK, Ioannidis JPA, Eluf-Neto J. Physical activity and cancer: an umbrella review of the literature including 22 major anatomical sites and 770 000 cancer cases. Br J Sports Med. 2018 Jul;52(13):826-833. doi: 10.1136/bjsports-2017-098391. Epub 2017 Nov 16.

Reference Type: BACKGROUND

PMID: 29146752 (View on PubMed)

Ashcraft KA, Peace RM, Betof AS, Dewhirst MW, Jones LW. Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation, Progression, and Metastasis: A Critical Systematic Review of In Vivo Preclinical Data. Cancer Res. 2016 Jul 15;76(14):4032-50. doi: 10.1158/0008-5472.CAN-16-0887. Epub 2016 Jul 5.

Reference Type: BACKGROUND

PMID: 27381680 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

IPD will be collected in the REDCap database. Since enrolment of patients has not started yet, no data has yet been entered. We are undecided on whether to share IPD with other researchers in future.

View Document

Other Identifiers

PAT1625724

Identifier Type: OTHER

Identifier Source: secondary_id

ImmuEX

Identifier Type: -

Identifier Source: org_study_id