Lung Neoplasms, Non Small Cell Lung Cancer
Conditions
Keywords
physical Activity
Brief summary
Recent advances combining chemotherapy and immunotherapy before surgery have significantly improved outcomes for patients with resectable non-small cell lung cancer (NSCLC). However, a substantial proportion of patients still do not respond optimally to these treatments. Researchers believe that physical activity may help strengthen the immune system and favorably modify the tumor microenvironment, potentially improving treatment effectiveness. ERICA-02 aims to investigate this hypothesis.The primary objective of ERICA-02 is to evaluate whether a structured exercise program performed during neoadjuvant chemo-immunotherapy can increase the presence of CD8+ cytotoxic T lymphocytes within the tumor. These immune cells play a key role in recognizing and destroying cancer cells and are considered an important marker of anti-tumor immune response.The study is designed for adults with locally advanced, resectable non-small cell lung cancer who are eligible for neoadjuvant chemo-immunotherapy followed by surgery. Participants must be medically fit to engage in physical activity, able to comply with study procedures, and provide informed consent before enrollment.ERICA-02 is a multicenter, randomized phase II pilot trial involving approximately 40 patients. Participants will be randomly assigned to one of two groups : intervention group and control group. Each participant will be involved in the study for approximately six months, including three months of exercise intervention for patients assigned to the exercise group.
Interventions
BEHAVIORALPhysical activity recommendations
At the baseline, all participants will receive the international recommendations in terms of physical activity for promoting health in the general population.
BEHAVIORALPhysical Activity (PA) Intervention
The exercise programme is carried out during the neoadjuvant period (9 to 12 weeks), alongside the three cycles of chemo-immunotherapy. Participants are provided with an exercise bike and a heart rate monitor. The programme is structured in three progressive phases: adaptation (weeks 1 to 3, light to moderate intensity), progression (weeks 4 to 6, increased intensity and introduction of interval training) and maintenance/optimisation (from week 7 until surgery, stabilisation of the training load). Outside the treatment weeks, participants undertake one supervised strength training session each week via videoconference and two independent aerobic sessions on an exercise bike. During each treatment session (C1, C2, C3), a supervised session combining aerobic exercise and strength training is carried out whilst the infusion is in progress.A weekly telephone follow-up allows the programme to be adjusted and enables the collection of assessments of fatigue and perceived exertion.
Sponsors
Centre Leon Berard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with locally advanced, resectable non-small cell lung cancer (NSCLC), stage IIA (≥ 4 cm) to IIIA according to the TNM classification (American Joint Committee on Cancer, 9th edition) * PD-L1 positive * ECOG performance status of 0 or 1 at diagnosis * Sufficient tumor material for the analyses planned by the study Note: The amount of available material must be validated by the coordinating center before patient enrollment * With measurable disease according to RECIST version 1.1 criteria * Recently diagnosed and eligible for neoadjuvant chemotherapy-immunotherapy, as decided by the multidisciplinary tumor board (MTB) * Having obtained medical certification of fitness to engage in physical activity, issued by the referring oncologist or the principal investigator * Willing and deemed likely to comply with the intervention and visit schedule and follow-up examinations throughout the duration of the study * Able to understand, read, and speak French * Affiliated with a social security scheme * Having been informed about the study and having signed an informed consent form
Exclusion criteria
* Activating EGFR mutations or ALK translocations, as well as those who have received prior chemotherapy, immunotherapy, or radiotherapy for their current lung cancer * History of cancer within the last 5 years * Uncontrolled cardiovascular disease, including heart failure, unstable coronary artery disease, severe arrhythmias, or uncontrolled hypertension that could limit participation in physical activity, according to the investigator * Uncontrolled type 2 diabetes despite appropriate treatment * Severe limiting pulmonary disease such as GOLD stage IV chronic obstructive pulmonary disease, or severe restrictive lung disease * Major neuropsychiatric disorders that could hinder participation in the program (e.g., dementia, Alzheimer's disease, advanced Parkinson's disease) * Severe physical disability or any other medical condition that contraindicates participation in an exercise program • Concurrent participation in another physical activity study * Pregnant woman * Person deprived of liberty by judicial or administrative decision, or adult protected by law
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the effect of a structured exercise program on immune pathological response (irPR) | T2 (pre-surgery): | Impact of structured exercise on the tumor immune microenvironment in patients receiving neoadjuvant chemo-immunotherapy. The primary endpoint is the density of CD8+ cytotoxic T lymphocytes (cells/mm²) within the tumor on the surgical specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate changes in the tumor immune microenvironment | Mainly pre surgery (T2), compared with baseline biopsy collected at inclusion (T1). | Assessment of stromal CD8+ CTL density, plasma cells (CD138/MUM1), mature tertiary lymphoid structures (CD20/CD23), and CTL/Treg (FOXP3) ratio. |
| Objective Response Rate (ORR) | From study inclusion until completion of the 3 planned neoadjuvant chemotherapy cycles, prior to surgery | Evaluate tumor response to neoadjuvant treatment. |
| Pathological Complete Response (pCR) | T2 (surgery) | Assess the absence of viable tumor cells in the surgical specimen. |
| Major Pathological Response (MPR) | T2 (surgery). | Evaluate residual tumor burden following neoadjuvant therapy. |
| Disease-Free Survival (DFS) | T3 (6 weeks post-surgery) and T4 (3 months post-surgery). | Evaluate recurrence-free survival following treatment. |
| Treatment-Related Toxicities | During the first, second, and third cycles of neoadjuvant chemotherapy ( Each cycle is separated by 21 days). | Incidence, nature, and severity of adverse events according to CTCAE v5.0. |
| Postoperative Complications | T3 (6 weeks post-surgery). | Incidence and severity of postoperative complications according to Clavien-Dindo classification. |
| Length of Postoperative Hospital Stay | Assessed 6 weeks after surgery (T3) | Number of hospital days following surgery. |
| 90-Day Postoperative Mortality | T4 (3 months post-surgery). | Mortality occurring within 90 days after surgery. |
| Change in Aerobic Capacity | at study inclusion and at the pre-surgery visit. | Measurement of submaximal oxygen consumption. |
| Change in Peripheral Muscle Strength | at study inclusion and at the pre-surgery visit. | Assessment of quadriceps isometric strength and core endurance (plank test). |
| Change in Functional Capacity | at study inclusion and at the pre-surgery visit. | Six-Minute Walk Test (6MWT) and handgrip strength. |
| Change in Functionnal capacity | at study inclusion and at the pre-surgery visit. | Handgrip test strength. |
| Change in Lean and Fat Mass | at study inclusion and at the pre-surgery visit. | Body composition analysis using (CT-scan) imaging at the L3 vertebral level and bioimpedance assessment |
| Level of physical activity | at study inclusion and at the pre-surgery visit. | International Physical Activity Questionnaire (IPAQ) score. The IPAQ assesses physical activity levels based on self-reported frequency and duration of physical activities. Higher scores indicate higher levels of physical activity. |
| Change in Quality of Life | at study inclusion and at the pre-surgery visit. | Evaluation using EORTC QLQ-F17 |
| Change of quality of life | at study inclusion and at the pre-surgery visit. | Evaluation using EORTC QLQ-LC13 questionnaires. |
| Change in Cancer-Related Fatigue | at study inclusion and at the pre-surgery visit. | Assessment using the FACT-Fatigue questionnaire. |
| Change in Circulating Immune and Inflammatory Biomarkers | At study inclusion, during the second cycle of neoadjuvant chemotherapy(Each cycle is separated by 21 days) and before surgery | Analysis of cytokines and myeloid/lymphoid cell populations using flow cytometry and MSD technology. |
| Participation Rate | At screening and 6 months | Proportion of eligible patients enrolled in the study. |
| Exercise Program Adherence | Assessed at study inclusion, during the first, second, and third cycles of neoadjuvant chemotherapy (each cycle is separated by 21 days), and at the pre-surgery visit | Exercise adherence measured as the percentage of prescribed exercise sessions completed. Values range from 0% to 100%, with higher percentages indicating greater adherence. |
| Attrition Rate | 6 months | Proportion of participants withdrawing from the study. |
| Program Acceptability and Satisfaction | pre-surgery (T2) : intervention arm only | Participant satisfaction with the exercise intervention, assessed using a self-administered questionnaire developed specifically for this study |
Countries
France
Contacts
CONTACTManon GOUEZ, Phd
CONTACTMeyssane Djebali, Msc
Outcome results
None listed