Impact of Physical Activity on Immunotherapy-induced Toxicities in Melanoma Management (APiTOXMM)

Management of melanoma is based on primary excision of the tumor. In cases of melanoma with poor prognosis criteria, or when it is locally advanced or metastatic, there is an indication for the implementation of adjuvant therapy, which may, in this context, be immunotherapy.

Immunotherapies are treatments that have revolutionized the prognosis of patients with melanoma. These are therapies that work by stimulating the immune system to enhance the anti-tumor response. Their toxicities are represented by immune-mediated toxicities, similar to true autoimmune diseases.

Adapted physical activity as supportive care in oncology is expanding. From a pathophysiological perspective, physical activity is thought to modulate the immune system (by reducing inflammation, restoring immune surveillance, stimulating anti-tumor responses through the induction of T cell proliferation, modulating the gut microbiota, and influencing tumor microenvironment cells, etc.).

The modulation of the immune system by physical activity may also allow us to hypothesize a modulation of the toxicities induced by immune checkpoint inhibitors. We wish to study this hypothesis in patients with advanced melanoma who are candidates for immunotherapy.

Originality and Innovative Aspects:

Physical activity as supportive care in oncology has developed significantly in recent years. However, adapted physical activity (APA) is currently only offered at one center in France (CHU de Lille).

In addition to the probable impact on patients' quality of life, if we find evidence supporting a reduction in treatment-related toxicities for melanoma through physical activity, it would be even more interesting to introduce APA at the CHU of Montpellier.

Primary and Secondary Objectives:

Primary Objective: To analyze the association between the level of physical activity (estimated by the IPAQ questionnaire) at the initiation of immunotherapy and the occurrence of adverse effects at 6 months after starting treatment in adult patients with melanoma.

Secondary Objectives:

Analyze the association between physical activity level and treatment efficacy of immunotherapy in adult melanoma patients.

Describe the quarterly evolution of patients' general condition through measurement of WHO status and BMI.

Assess the evolution of patients' general condition: WHO status and BMI at treatment introduction, after 3 months, and at 6 months of treatment.

Study the evolution of patients' quality of life during their treatment based on their physical activity level, using the QLQ-C30 questionnaire.

Preliminary study:

We aim to evaluate the correlation between self-reported physical activity by patients and their actual physical activity. To obtain an objective measurement of patients' physical activity level, we plan to work with the CARTIGEN platform and offer a small number of included patients (maximum of 50) to wear wrist actimeters for one week before treatment initiation. We will then analyze these data to determine patients' baseline physical activity levels and compare them with the data collected via questionnaires.

This is a prospective cohort study within the context of analytical epidemiological research. It is a bicentric study: CHRU Montpellier - Saint-Eloi Hospital and ICM Val d'Aurelle.

Using the collected data on patients' physical activity levels (IPAQ questionnaire), we will compare two groups: patients who experienced immuno-toxicities without physical activity versus those with moderate or high physical activity.

We will also analyze treatment efficacy in these two groups, patients' quality of life, and the evolution of their general condition.

Procedure:

Inclusion is planned at day 0 (D0), with physical activity (IPAQ3) and quality of life (QLQ-C30) questionnaires, along with clinical and oncological evaluation.

A follow-up visit at month 3 (M3) will include reassessment of clinical and oncological status, followed by another visit at month 6 (M6) for further clinical, oncological, physical activity, and quality of life reassessment.

The inclusion period is expected to last 18 months.

Outcomes / Perspectives:

If we consider that physical exercise may help mitigate the toxic effects of treatments-an aspect we wish to explore through this project-it would be relevant to introduce adapted physical activity (APA) sessions supervised by a specialized instructor within the Dermatology Day Hospital at the CHU of Montpellier.

Implementing APA in the context of onco-dermatology will strengthen the multidisciplinary approach of the CHU.

Collaboration between healthcare professionals, including specialized APA instructors, will foster effective care coordination.

This initiative is part of a holistic approach to patient care, integrating complementary interventions to address physical, psychological, and social needs.

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Immunotoxicity
• Intervention / Treatment: Drug: Immunotherapy

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

• Study Contact: Name: Alexandre Maria, MD, PhD; Phone Number: 00330665849253; Email: a-maria@chu-montpellier.fr
• Study Contact Backup: Name: Quentin Samaran, MD, MSc; Phone Number: 00330467336906; Email: q-samaran@chu-montpellier.fr

Study Locations

• France
  • Montpellier, France
    • Recruiting
    • CHU de Montpellier
    • Contact: Alexandre Maria, MD, PhD; Phone Number: 00330665849253; Email: a-maria@chu-montpellier.fr
  • Montpellier, France
    • Not yet recruiting
    • Institut du Cancer de Montpellier (ICM)
    • Contact: Anouck Lamoureux, MD; Phone Number: 00330467336906; Email: a-lamoureux@chu-montpellier.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Subjects aged 18 years or older, newly diagnosed with melanoma with an indication for treatment initiation by immunotherapy (anti-PD1 or anti-PD1 + anti-CTLA4), in an adjuvant or metastatic setting. Only incident cases will be included. Patients treated at Montpellier University Hospital (CHU) or the Montpellier Cancer Institute (ICM)

Description

Inclusion Criteria:

• age 18 years or above
• ECOG performance status inferior or equal to 3
• patient with a melanoma confirmed histologically/pathologically
• indication for initiating treatment with anti-PD1 immunotherapy or anti-PD1 + anti-CTLA4

Exclusion Criteria:

• patient unable to read and/or write
• inability to follow up with the patient during the study period
• refusal to participate after a reflection period
• medical contraindication to initiating immunotherapy (active autoimmune disease requiring systemic treatment in the past 2 years, active infection, etc.)
• not affiliated with a social security system
• patient under legal protection, guardianship, or curatorship
• person participating in another study that includes an ongoing exclusion period

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with no physical activity / low physical activity; Patients with low score according to the IPAQ questionnaire at baseline. This is the lowest level of physical activity.	Drug: Immunotherapy; Patients will be treated in accordance with the guidelines for melanoma treatment.; Other Names: pembrolizumab; ipilimumab; nivolumab
Patients with moderate to high physical activity; Patients with moderate or high score according to the IPAQ questionnaire at baseline.	Drug: Immunotherapy; Patients will be treated in accordance with the guidelines for melanoma treatment.; Other Names: pembrolizumab; ipilimumab; nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunotoxicity	Occurrence of immune-induced side effects	From the time of enrollment until 6 months following the initiation of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of immunotherapy	Tumoral response to immunotherapy	From the time of enrollment until 6 months following the initiation of treatment

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 2, 2024
• First Submitted That Met QC Criteria: October 2, 2024
• First Posted (Actual): October 4, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: physical activity; immunotherapy; melanoma; anti-PD-1; anti-CTLA4; immunotoxicity
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab; Ipilimumab; Pembrolizumab
• Other Study ID Numbers: RECHMPL24_0195

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No