Feasibility of an Acute Physical Exercise Before Treatment Infusion for Metastatic Lung Cancer Patients

Carcinoma, Non-Small-Cell Lung Clinical Trial

— ERICA  

Official title:

Feasibility of an Acute Physical Exercise Before Immunotherapy and Chemotherapy Infusion for Metastatic Non-small-cell Lung Cancer Patients: Protocol ERICA Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04676009
• Other study ID #: ERICA
• Secondary ID: ET20000185
• Status: Completed
• Phase: N/A
• Start date: January 21, 2021
• Est. completion date: January 11, 2024

Study information

• Verified date: February 2024
• Source: Centre Leon Berard
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Because of metastatic Non-Small Cell Lung Cancer (mNSCLC) and its treatments, patients suffer from numerous symptoms such as dyspnea, muscle atrophy, pain, fatigue, loss of appetite, altered physical condition and lung function, which may further impair the patient's overall condition. Nevertheless, it has been suggested that physical exercise could improve response to treatment at the clinical level due to its known effects on the immune system. Moreover, preclinical studies have shown that exercise performed during chemotherapy administration could result in physiological benefits such as improved intra-tumoral infusion and drug delivery. The ERICA study aims to assess the feasibility of an acute physical exercise immediately before immunotherapy and chemotherapy administration in patients with mNSCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 11, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 80 years old,

• Having a newly metastatic non-small-cell lung cancer (NSCLC) without an EGFR/ALK alteration diagnosis,

• Being scheduled to receive a 1st line intravenous chemotherapy (Cisplatin and Pemetrexed or Carboplatin and Pemetrexed or Taxol and Carboplatin), and immunotherapy (monoclonal anti-PD-1 and anti-PD-L1 antibodies : Pembrolizumab) treatment NB : patients who have previously received one or more treatments other than chemotherapy (e.g. targeted therapy) and must start their first chemotherapy are eligible,

• Treated in Centre Leon Berard,

• Having an Eastern Co-operative Oncology Group (ECOG) performance status = 2,

• Being voluntary and available to get involved throughout the study duration,

• Being able to engage in Physical Activity with a medical certificate attested by one of the investigators clinical oncologist or the referring oncologist,

• Affiliated with a social security scheme,

• Having dated and signed an informed consent.

• Able to read, write and understand French

Exclusion Criteria:

• Patient with unstable bone metastases or unconsolidated pathologic fractures, Having a central nervous system impairment with neurological disorder avoids the physical exercise practice on a cycle ergometry,

• Personal history or co-existence of another primary cancer (except of in situ cancer regardless of the site and/or basal cell skin cancer and/or cancer in complete remission for more than 5 years),

• Having severe undernutrition defined according to the Haute Autorité de Santé (i.e. , for an adult aged =18 years and < 70 : BIM = 17 or weight loss = 10% in 1 month or =15% in 6 months or = 15% compared to the usual weight before the disease diagnosis or albuminemia < 30 g/l ; for an adult aged =70 years : BIM < 18 or weight loss = 10% in 1 month or =15% in 6 months or an albuminemia < 30 g/l),

• Having a severe amenia (hemoglobin = 8 g/dl) during the 30 last days prior inclusion,

• Presenting cardiovascular history or any cardiovascular risk: chronic coronary (or poorly balanced), artery disease, cardiac arrhythmia, symptomatic heart disease, uncontrolled or untreated hypertension, heart attack diagnosed within the last 6 months, coronary angioplasty with or without stent less than 6 months old, coronary artery bypass surgery less than 12 months old, history of poorly balanced type 2 diabetes,

• In case of diabetes: Glycated hemoglobin (HbA1c) > 7% (in the last 3 months),

• Stage IV Chronic Obstructive Pulmonary Disease (FEV1 < 30%),

• Patient with a contraindication to the proposed physical exercise in the study (orthopedic disorder likely to impede walking and pedaling such as disabling coxarthrosis or gonarthrosis, operated or not),

• Already included in a PA study,

• Cannot be followed for medical, social, family, geographical or psychological reasons, for the duration of the intervention (3 months) and then for the duration of the post-intervention follow-up (3 months),

• Patient under legal protection measure (under guardianship, curatorship, safeguard of justice),

• Deprived of liberty by judicial or administrative decision,

• Pregnant patient.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Other:
• Exercise arm :
Patients will receive physical activity recommendations at inclusion. At each treatment cure, patients will receive pre-exercise nutritional recommendations and an acute physical exercise prior to immunotherapy and chemotherapy. The acute physical exercise will last 35 minutes and will be intermittent and individualized based on the results obtained by the patient during an endurance test on a ergocyle performed prior to treatment. 3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place before exercise (1), after exercise (2) and 12 hours after the start of treatment (3). A nutritional assessment will be carried out during the first and last treatment cure. They will also benefit a home walking program. These patients will have to wear an activity tracker tracker during all intervention (3 months). They will have a phone follow-up every 10 days (± 3 days) after each treatment cure for the study duration.

Locations

Country	Name	City	State
France	Centre Léon Bérard	Lyon

Sponsors (5)

Lead Sponsor	Collaborator
Centre Leon Berard	Claude Bernard University, Hospices Civils de Lyon, Inter-university Laboratory of Human Movement Biology, Lyon Cancer Research Centre

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigate the feasibility of an acute physical exercise during the immunotherapy/chemotherapy preinfusion	Ratio of the number of acute physical exercise sessions immunotherapy/chemotherapy preinfusion performed by"exercise" group patient / number of acute physical exercise sessions planned	3 months
Secondary	Investigate the physical activity fitness (sub-maximum endurance test)	Sub-maximum endurance test on an ergocycle	Baseline, 3 months
Secondary	Investigate the lower strength muscular function change	Maximum isometric force of the knee extensors	Baseline, 3 months, 6 months
Secondary	Investigate the maximum isometric upper limb strength change	Hand dynamometer	Baseline, 3 months, 6 months
Secondary	Investigate the Physical Activity level change	The PA level will be measured by the Godin Leisure-Time Physical Activity Questionnaire (GLTAPQ). The GLTAPQ is a 4-item self-administered questionnaire with the first three questions designed to obtain information on the number of times an individual engages in light, moderate and intense "leisure-time PA" periods of at least 15 minutes during a typical week. The scoring of the GSLTPAQ is the "LSI" (Leisure Score Index) is obtained using the following formula: (light PA frequency × 3) + (moderate PA frequency × 5) + (vigorous PA frequency × 9). People with a moderate to high LSI = 24 are classified as active, while people reporting a moderate to high LSI = 23 are classified as insufficiently active (estimated energy expenditure < 14 Kcal/kg/week).	Baseline, 3 months, 6 months
Secondary	Investigate the patient anthropometrics change	Weight in kilograms	Baseline, 3 months, 6 months
Secondary	Investigate the patient anthropometrics change	Hip circumference in centimeters	Baseline, 3 months, 6 months
Secondary	Investigate the patient anthropometrics change	Waist circumference in centimeters	Baseline, 3 months, 6 months
Secondary	Investigate the patient anthropometrics change	BMI (weight/height²)	Baseline, 3 months, 6 months
Secondary	Investigate the patient health-related quality of life change	Quality of life will be measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality Of Life Questionnaire (QLQ-C30). Quality of life specific to lung cancer will be assessed by the 13-item module: The Quality Of Life Questionnaire - Lung Cancer 13 (QLQ-LC13). The QLQ-LC13 self-questionnaire is an additional measure of the symptoms and side effects experienced by lung cancer patients who receive non-surgical treatment.	Baseline, 3 months, 6 months
Secondary	Investigate the patient health-related quality of life specific to lung cancer change	Quality of life specific to lung cancer will be assessed by the 13-item module: The Quality Of Life Questionnaire - Lung Cancer 13 (QLQ-LC13). The QLQ-LC13 self-questionnaire is an additional measure of the symptoms and side effects experienced by lung cancer patients who receive non-surgical treatment.	Baseline, 3 months, 6 months
Secondary	Investigate the fatigue change	Fatigue will be assessed by the EORTC-QLQ module measuring cancer-related fatigue (EORTC QLQ-FA12). This self-questionnaire includes 12 items that assess physical, cognitive and emotional fatigue related to cancer. Participants will respond on a Likert scale ranging from "not at all" to "a lot". All scores will be transformed into a scale from 0 to 100, with a higher score indicating a higher degree of fatigue.	Baseline, 3 months, 6 months
Secondary	Investigate the sleep quality change	The perceived quality of sleep is assessed by the Insomnia Severity Index (ISI) which measures the severity of insomnia. The questionnaire consists of 7 items rated on a 5-point scale ranging from 0 ("none") to 4 ("very severe"). This self-questionnaire makes it possible to evaluate the severity of the patient's sleep difficulties (initial, maintenance, morning insomnia), the degree of sleep dissatisfaction, the level of interference with daily functioning, the degree of appearance of sleep difficulties and the level of anxiety related to insomnia. The total score of the items varies between 0 and 28. A high score indicates greater sleep difficulties.	Baseline, 3 months, 6 months
Secondary	Investigate the impact of social vulnerability	Social vulnerability will be assessed by the EPICES score (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé). By adding up the points of the 11 binary questions ("Yes"/"No") of the self-questionnaire we obtain the so-called EPICES score. This quantitative score varies from 0 "no precariousness" to 100 "highest precariousness".	Baseline
Secondary	Investigate the muscle mass and sarcopenia	CT scans	Baseline, 3 months, 6 months
Secondary	Investigate the immune biomarkers change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).; The following immune biomarkers will be assay : Natural Killer cells, B lymphocytes, T lymphocytes, monocytes, sub-populations of dendritic cells on frozen PBMC	Baseline and 3 months
Secondary	Investigate the Activin change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the TNF-alpha change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the IL-1béta change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the IL-6 change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Follistatin (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the GDF5 (BMP14) (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the GDF15 (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the IL-10 (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the IL-15 (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the NH3 (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Aminogramme (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the CRP (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the IFN-gamma change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Cortisol change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Myostatin change (inflammation biomarkers)	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Advanced oxidation protein products (AOPP) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the Superoxide dismutase (SOD) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the catalase (CAT) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the malondialdehyde (MDA) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).; The following biomarkers will be assay : Advanced oxidation protein products (AOPP), malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Xanthine oxidase (XO), and Myeloperoxidase (MPO).	Baseline and 3 months
Secondary	Investigate the glutathione peroxidase (GPX) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).; The following biomarkers will be assay : Advanced oxidation protein products (AOPP), malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Xanthine oxidase (XO), and Myeloperoxidase (MPO).	Baseline and 3 months
Secondary	Investigate the Xanthine Myeloperoxidase (MPO) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).; The following biomarkers will be assay : Advanced oxidation protein products (AOPP), malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Xanthine oxidase (XO), and Myeloperoxidase (MPO).	Baseline and 3 months
Secondary	Investigate the Xanthine oxidase (XO) change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).; The following biomarkers will be assay : Advanced oxidation protein products (AOPP), malondialdehyde (MDA), Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Xanthine oxidase (XO), and Myeloperoxidase (MPO).	Baseline and 3 months
Secondary	Proportion of patients who have severe toxicity (grade >2)	Occurence of severe toxicity (grade > 2) according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE). Number of delayed or cancelled treatment sessions and relative dose-intensity (RDI) for patients with grade = 3 chemotherapy-related toxicities, calculated as the ratio of the "delivered" dose-intensity to the "expected" dose-intensity.	Up to 3 months
Secondary	Progression free survival	Period from the date of randomization to the date of event defined as disease progression or death from any cause	6 months
Secondary	Acceptability of the study	Ratio of the number of patients included / number of eligible patients	3 months
Secondary	Tracker activity acceptability	Number of days the activity tracker is worn / number of days in the programme	3 months
Secondary	Safety of the intervention	Number, type and timing of adverse events due to program	3 months
Secondary	Adherence of the intervention	number of steps at home realized / number of steps at home prescribed (only in the intervention arm)	3 months and 6 months
Secondary	Investigate the Physical Activity level change	Daily number of step prescription (only in the intervention arm)	Baseline, 3 months and 6 months
Secondary	Investigate the glucose change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the insulin change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the lactat change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the PCR change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months
Secondary	Investigate the HIF-1 change	3 blood sampling times (2 EDTAsx10 mL) will be specially added to the study and will take place: for the exercise group: before exercise (1), after exercise (2) and 12 hours after the start of treatment (3); and for the control group: 40 min before the administration of treatments (1), just before the administration of treatments (2) and 12 hours after the start of treatment(3).	Baseline and 3 months