ERICA-02 Study : Impact of Physical Exercise on the Tumor Immune Microenvironment in Patients Treated With Neoadjuvant Chemoimmunotherapy for Non-small Cell Lung Cancer

N/ANot Yet RecruitingNCT07786909

Centre Leon Berard40 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

Conditions

Lung Neoplasms

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Evaluate the effect of a structured exercise program on immune pathological response (irPR)

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.

Time frame: T2 (pre-surgery):

Secondary Outcomes

Evaluate changes in the tumor immune microenvironment

Assessment of stromal CD8+ CTL density, plasma cells (CD138/MUM1), mature tertiary lymphoid structures (CD20/CD23), and CTL/Treg (FOXP3) ratio.

Time frame: Mainly pre surgery (T2), compared with baseline biopsy collected at inclusion (T1).

Objective Response Rate (ORR)

Evaluate tumor response to neoadjuvant treatment.

Time frame: From study inclusion until completion of the 3 planned neoadjuvant chemotherapy cycles, prior to surgery

Pathological Complete Response (pCR)

Assess the absence of viable tumor cells in the surgical specimen.

Time frame: T2 (surgery)

Major Pathological Response (MPR)

Evaluate residual tumor burden following neoadjuvant therapy.

Time frame: T2 (surgery).

Disease-Free Survival (DFS)

Evaluate recurrence-free survival following treatment.

Time frame: T3 (6 weeks post-surgery) and T4 (3 months post-surgery).

Treatment-Related Toxicities

Incidence, nature, and severity of adverse events according to CTCAE v5.0.

Time frame: During the first, second, and third cycles of neoadjuvant chemotherapy ( Each cycle is separated by 21 days).

Postoperative Complications

Incidence and severity of postoperative complications according to Clavien-Dindo classification.

Time frame: T3 (6 weeks post-surgery).

Length of Postoperative Hospital Stay

Number of hospital days following surgery.

Time frame: Assessed 6 weeks after surgery (T3)

90-Day Postoperative Mortality

Mortality occurring within 90 days after surgery.

Time frame: T4 (3 months post-surgery).

Change in Aerobic Capacity

Measurement of submaximal oxygen consumption.