Exercise in Patients With Advanced Non-small Cell Lung Cancer (BREATH)

Better Symptom Control With Exercise in Patients With Advanced Non-small Cell Lung Cancer

Lung cancer is one of the most common types of cancer in Germany, with 56,839 new cases and 45,072 deaths annually. Approximately 70% of patients with non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage and suffer from comorbidities and symptoms such as fatigue, tiredness, and loss of strength. The standard first-line treatment for metastatic NSCLC includes platinum-based chemoimmunotherapy followed by immunotherapy maintenance. Exercise can have positive effects on symptoms such as shortness of breath, fatigue, quality of life, and physical fitness. However, there is a lack of current scientific evidence for the effectiveness of exercise in advanced lung cancer patients. No current trial investigated exercise in advanced NSCLC receiving immunotherapy so far.

The BREATH-study is a prospective 3-arm randomized controlled trial (RCT). In total, the investigators plan to recruit 104 patients. A 2:1:1 randomization will be performed with three study groups: a control group and two exercise therapy groups (strength+endurance exercise/only endurance exercise). One group receives individual endurance training and the other group a combination of individual endurance and strength training. Both treatment groups will be treated twice a week for 12 weeks. The control group will initially receive standard treatment without exercise for 12 weeks and will then be randomized into one of the other two study groups with exercise twice a week for 12 weeks. This approach allows for a sufficiently large sample for comparisons between exercise therapy and the control group, as well as between the two exercise therapy approaches.

The primary aim is to investigate the impact of exercise on V02peak. Secondarily endpoints aim to investigate changes in physical function, patient related outcomes and cardiac function before and after exercise.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Lung Carcinoma; NSCLC Stage IV; NSCLC Stage IIIB; First Line Treatment; Second Line Treatment; Palliative Treatment; NSCLC Stage IIIC
• Intervention / Treatment: Behavioral: Exercise intervention

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nico De Lazzari, M. Sc.; Phone Number: +49 201 / 723-82035; Email: nico.delazzari@uk-essen.de
• Study Contact Backup: Name: Mitra Tewes, PD. Dr.; Phone Number: +49 201 723 7262; Email: mitra.tewes@uk-essen.de

Study Locations

• Germany
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45147
      • West German Cancer Center (Department of Palliative medicine and Department of Medical Oncology), University Hospital Essen
      • Contact: Mitra Tewes, PD. Dr.; Email: mitra.tewes@uk-essen.de
      • Contact: Nico De Lazzari, M. Sc.; Phone Number: +49 201 723-82035; Email: nico.delazzari@uk-essen.de
      • Principal Investigator: Mitra Tewes, PD. Dr.
      • Sub-Investigator: Marcel Wiesweg, PD. Dr.
      • Sub-Investigator: Miriam Götte, PD. Dr.
      • Sub-Investigator: Eva-Maria Hüßler, Dr.
      • Sub-Investigator: Andreas Stang, Prof. Dr.
      • Sub-Investigator: Matthias Totzeck, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Patients with histologically confirmed non-small cell lung carcinoma in UICC stages IIIB and IV
• First- or second-line therapy (inclusion up to 28 days after the first cycle) in palliative intention
• Age ≥ 18 years
• Signed informed consent

Exclusion Criteria

• Severe cardiopulmonary disease (EF<30%)
• Newly occurring or progressive uncontrolled CNS (central nervous system) metastases
• Expected life expectancy < 3 months
• Bone metastases with acute risk of fracture
• ECOG (Eastern Cooperative Oncology Group) performance status > 2
• Acute pulmonary embolism
• Acute myocardial infarction
• Requiring surgery for aortic aneurysm
• Tension pneumothorax
• Lack of proficiency in the German language
• Active infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (endurance training + strength training); Frequency: 2 supervised exercise sessions per week. Session Breakdown: Duration: 60 minutes per session. Aerobic Endurance Training: 20 minutes. Strength Training: 40 minutes. Aerobic Interval Training: Set at 50% of maximal workload based on spiroergometry. Five sets of 2 minutes of exertion; 5 sets of 1 minute of recovery; Total exertion time: 20 minutes Strength Training: Muscle Groups Targeted: Major muscle groups. Sets and Repetitions: 2 sets with 8-12 repetitions. Training Intensity: Range: 50-80% of 1-RM (1-repetition maximum)	Behavioral: Exercise intervention; Exercise
Experimental: Arm B (endurance exercise); Frequency: 2 supervised exercise sessions per week. Session Breakdown: Duration: Approximately 30 minutes. Focus: Aerobic endurance training. Followed by 10 minutes of Respiratory therapy. Endurance Training: Method: Intervals for a balance between exertion and recovery. Intensity: Set at 50% of maximal workload based on spiroergometry.	Behavioral: Exercise intervention; Exercise
No Intervention: Arm C (Usual Care); The control group receives a one-time sports consultation with general information about daily activities and sports participation, as well as individual training recommendations. After the 12 weeks, the control group will be randomized into one of the exercise therapies.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum oxygen uptake (VO2 peak [ml/min/kg])	The primary goal is to achieve an improvement in performance (VO2 peak[ml/min/kg]) from T0 (enrolment) to T1 (12 weeks) through exercise compared to the standard treatment. The one-sided alternative hypothesis of a larger improvement in the two treatment groups compared to the control group will be tested statistically as a confirmatory analysis.	assessed at Baseline, after 12 weeks and 24 weeks of enrolment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Assessment of Chronic Illness Therapy - Fatigue (FACT-F)	The FACT-F is a 13-item questionnaire to assess fatigue in cancer patients. Subscale are physical well-being, social/family well-being, emotional well-being, functional well-being and the fatigue subscale. Based on the subscale the FACIT-F trial outcome index (TOI) Score range 0-108, FACT-G total score (Score range 0-108) and FACIT-F total score (Score range 0-160) can be calculated. The higher the score, the better the Quality of Life.	assessed at baseline, after 12 weeks and 24 weeks of enrolment
European Organisation for Research and Treatment of Cancer (EORTC QLQ C30)	The EORTC QLQ Core Questionnaire is a 30-item instrument meant to assess some of the different aspects that define the quality of life of cancer patients (e.g., physical function, emotional function, symptom scales, and Quality of Life). High scores for functional scales (score 0-100) represent a high level of functioning, high scores for the global health status represent a high quality of life (score 0-100), high scores for symptom scales (score 0-100) represent a high level of symptomatology.	assessed at baseline after 12 weeks and 24 weeks of enrolment
European Organisation for Research and Treatment of Cancer Lung cancer module (EORTC-LC13)	The LC13 is a modular supplement to the EORTC-C30 for assessment of symptoms in clinical lung. cancer trials. The scoring range is between 0 to 100, a high score indicating a high level of symptomatology.	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Arterial blood pressure	Change during study participation (mmHg)	assessed at Baseline, after 12 weeks and 24 weeks of enrolment
Change in ECG	Changes in 12-lead resting ECG, including PQ [ms], QRS [ms], and QT [ms] intervals	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Adherence to exercise intervention	The exercise physiologist monitored adherence to the supervised sessions. Based on the absolute numbers of scheduled exercise sessions, both absolute and percentage-based adherence can be calculated and compared between study arms.	Through study completion, an average of 12 weeks
Drop-out rate	All withdrawals will be considered as dropouts, with reasons noted. Compare the total number of dropouts in each study arm. This provides a straightforward comparison of the raw dropout counts between groups. Also, calculate the percentage of participants who dropped out in each study arm relative to the total number of participants initially assigned to that arm. This allows for a comparison of dropout rates relative to the initial sample size and compared between study arms.	Through study completion, an average of 12 weeks
Recruitment rate	The recruitment rate quantifies the speed of participant enrollment for a study.	At Baseline
Serious Adverse Event/Adverse Events	Safety analyses will be based on Adverse Events (AEs), Serious Adverse Events (SAEs) after the Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Through study completion, an average of 12 weeks
Therapy response	Therapy response in the next computer tomography (analogous to RECIST v1.1)	Baseline and after 12 weeks
Treatment Toxicity	Treatment toxicity encompasses the adverse effects experienced by individuals undergoing chemotherapy and exercise regimens concurrently. These effects may manifest as physical symptoms such as fatigue, nausea, muscle weakness, and decreased immune function, which can impact overall well-being and treatment adherence. Monitoring and managing toxicity levels are crucial to ensure patient safety and optimize treatment outcomes. Additionally, integrating exercise interventions alongside chemotherapy may pose unique challenges, as physical activity can exacerbate certain side effects or interact with treatment efficacy. Therefore, careful monitoring and personalized exercise prescriptions are essential to mitigate toxicity risks and enhance the overall tolerability and effectiveness of combined therapy approaches. Toxicity will be reported with CTCAE v5.0	assessed at baseline after 12 weeks and 24 weeks of enrolment
Treatment scheme	Change in dose or frequency during trial participation	assessed at baseline after 12 weeks and 24 weeks of enrolment
NT-pro-BNP	Concentration of N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP), measured in picograms per milliliter (pg/mL) of blood	Up to 24 weeks
High sensitive troponin I	Concentration of troponin I in nanograms per milliliter [ng/mL] of blood.	Up to 24 weeks
Erythrocytes	The amount of Erythrocytes per liter [/pl]	Up to 24 weeks
Hemoglobin	Concentration of hemoglobin in the blood, measured in grams per deciliter (g/dL)	Up to 24 weeks
Leukocytes	Count of leukocytes per nanoliter [ /nl]	Up to 24 weeks
Lymphocytes	Count of lymphocytes per nanoliter [ /nl]	Up to 24 weeks
Neutrophils	Count of neutrophils per nanoliter [ /nl]	Up to 24 weeks
CRP	Concentration of C-reactive protein (CRP) in the blood, measured in milligrams per deciliter [mg/dL]	Up to 24 weeks
CYRFRA 21-1	Concentration of cytokeratin-19 fragment (CYFRA 21-1) in nanograms per milliliter [ng/mL] of blood	Up to 24 weeks
Physical function (Hypothetical One-repetition maximum)	Leg press [kg.], Latissimus pulldown [kg.], bench press [kg.], Crunch [kg.], Leg curl [kg.], Back extension [kg.]	assessed at baseline after 12 weeks and 24 weeks of enrolment
Blood gas analysis pH value	pH value	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (PAO2)	Partial pressure of oxygen in arterial blood (PAO2 [mmHg])	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (SaO2)	Arterial oxygen saturation, measured as a percentage (SaO2 [%])	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (PCO2)	Partial pressure of carbon dioxide in arterial blood PCO2 [mmHg]	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (BE)	Base excess (BE) represents the amount of excess or deficit of base (primarily bicarbonate, HCO3-) in the blood [mmol/l]	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (HCO3)	Bicarbonate concentration in the blood HCO3 [mmol/l]	assessed at baseline, after 12 weeks and 24 weeks of enrolment
Blood gas analysis (SBCe)	Bicarbonate Concentration in the extracellular fluid SBCe [mmol/l]	assessed at baseline, after 12 weeks and 24 weeks of enrolment

Collaborators and Investigators

• Sponsor: University Hospital, Essen
• Collaborators: German Cancer Aid
• Investigators: Principal Investigator: Mitra Tewes, PD. Dr., Department of Palliative Medicine, University Hospital Essen

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 70115371

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We will publish a study protocol, including the statistical analysis plan, at an international peer-reviewed journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No