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NCT Number: NCT07761871

Exercise and Nutritional Intervention in Patients With Melanoma Receiving Immunotherapy

The purpose of this randomized study is to evaluate whether a six-month program of structured resistance exercise combined with individualized nutritional support can preserve or improve skeletal muscle mass and muscle quality in adults with stage II to IV malignant melanoma who are starting treatment with immune checkpoint inhibitors.

Participants will be randomly assigned either to the exercise and nutritional intervention in addition to standard oncology care or to standard oncology care alone. The study aims to obtain complete measurements from at least 40 participants.

Assessments will be performed at baseline, after 3 months, and after 6 months. They will include magnetic resonance imaging of the thigh, dual-energy X-ray absorptiometry, bioelectrical impedance analysis, indirect calorimetry, clinical data, and patient-reported outcomes. The study will compare changes in skeletal muscle mass and volume, fatty infiltration of skeletal muscle, sarcopenia, body composition, resting energy expenditure, quality of life, fatigue, treatment tolerance, treatment delays, and early treatment discontinuation between the two groups.

Treatment with immune checkpoint inhibitors is provided as part of routine clinical care and is not the investigational intervention.

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Key information

Conditions

Melanoma Atrophy Muscular Atrophy Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Nervous System Diseases Neuroectodermal Tumors Neuroendocrine Tumors Neurologic Manifestations Neuromuscular Manifestations Nevi and Melanomas Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Sarcopenia Signs and Symptoms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Institute of Oncology Ljubljana

Ljubljana, 1000, Slovenia

Location status: Recruiting

Location contact

Nada Rotovnik Kozjek

PRINCIPAL_INVESTIGATOR

Nada Rotovnik Kozjek, MD, PhD

CONTACT

[email protected]

+38641 612 541

About this study

MEL-FIT-IO is an umbrella randomized interventional study evaluating a six-month structured resistance exercise and individualized nutritional intervention in patients with malignant melanoma receiving immune checkpoint inhibitors.

Two prespecified doctoral substudies are embedded within the parent study and use the same participants, study groups, randomization, and assessment schedule. No separate randomization is performed for the substudies.

The ultrasound substudy, protocol ORI2026-5 (US-MUMELICI), evaluates the validity and longitudinal responsiveness of skeletal muscle ultrasound. Rectus femoris shear-wave velocity, muscle stiffness, echogenicity, and thigh muscle thickness are compared with magnetic resonance imaging, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis at baseline, 3 months, and 6 months.

The myokine and metabolic substudy, protocol ORI2026-35 (MY-MEL-FIT-IO), evaluates changes in circulating myokines, systemic inflammatory and immune-cell markers, metabolic parameters, body composition, treatment tolerance, and patient-reported outcomes. Biomarker analyses are performed in the prespecified subgroup of participants with metastatic melanoma.

Treatment with immune checkpoint inhibitors is provided as part of routine clinical care and is not the investigational intervention.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 years or older.
  • Confirmed diagnosis of malignant melanoma, stage II, III, or IV.
  • Planned first-line or adjuvant treatment with immune checkpoint inhibitors.
  • Life expectancy greater than 6 months.
  • Sufficient knowledge of the Slovenian language.
  • Ability to provide written informed consent and comply with the study protocol.

Exclusion criteria

  • Previous treatment with immune checkpoint inhibitors or disease recurrence after previous treatment with immune checkpoint inhibitors.
  • Symptomatic brain metastases.
  • Contraindications to magnetic resonance imaging, such as MRI-incompatible metallic implants.
  • Neurological diseases affecting the skeletal muscular system, such as muscular dystrophy.
  • Any condition that, in the investigator's judgment, prevents participation or the safe performance of study assessments.
  • Participation in another study that includes structured physical exercise as part of its protocol.

Treatment and study plan

Structured Resistance Exercise

Behavioral

A 24-week supervised and progressive whole-body resistance exercise program performed three times per week under the guidance of trained exercise professionals. Each session will last approximately 60 minutes and will include resistance exercises targeting the major muscle groups of the upper and lower body. Exercise intensity will progressively increase from approximately 60% to 70% of one-repetition maximum. A deload week at approximately 60% of one-repetition maximum will be scheduled every fourth week. Training load will be adjusted using repeated one-repetition maximum assessments and the Borg Rating of Perceived Exertion Scale. Exercise will not be performed on the day before study assessments to avoid acute effects on the measurements.

Individualized Nutritional Support

Behavioral

Individualized nutritional assessment and counseling provided by a clinical dietitian in cooperation with a physician specializing in clinical nutrition. Energy requirements will be determined using indirect calorimetry. The nutritional strategy will target a daily protein intake of 1.5 to 2 g/kg of body weight and a daily fiber intake of 30 to 40 g. Participants will receive 30 g of whey protein to be consumed within one hour after each exercise session. Oral nutritional supplements and other appropriate nutritional therapy will be prescribed when clinically indicated, including in participants with inadequate intake, malnutrition, cachexia, or sarcopenia.

Primary outcomes

  1. Change From Baseline in Thigh Skeletal Muscle Volume Assessed by Magnetic Resonance Imaging

    Time frame: Baseline and 6 months

    Thigh skeletal muscle volume will be quantified using magnetic resonance imaging. The change from baseline to 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group.

  2. Change From Baseline in Skeletal Muscle Fat Infiltration Assessed by Magnetic Resonance Imaging

    Time frame: Baseline and 6 months

    Skeletal muscle fat infiltration in the thigh will be quantified using magnetic resonance imaging. The change from baseline to 6 months will be compared between the two study groups.

  3. Number of Participants With Sarcopenia at 6 Months

    Time frame: Baseline and 6 months

    Sarcopenia will be assessed based on study measurements of skeletal muscle mass and muscle function. The number and proportion of participants with sarcopenia at 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group, taking baseline sarcopenia status into account.

Secondary outcomes

  1. Mean Change From Baseline in Resting Energy Expenditure Assessed by Indirect Calorimetry

    Time frame: Baseline and 6 months

    Resting energy expenditure will be measured using indirect calorimetry. The mean change from baseline to 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group.

  2. Change From Baseline in Lean Body Mass Assessed by Dual-Energy X-Ray Absorptiometry

    Time frame: Baseline, 3 months, and 6 months

    Lean body mass will be assessed using dual-energy X-ray absorptiometry. Changes from baseline at 3 months and 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group.

  3. Mean Change From Baseline in Total Body Fat Mass Assessed by Dual-Energy X-Ray Absorptiometry

    Time frame: Baseline, 3 months, and 6 months

    Total body fat mass will be measured in kilograms using dual-energy X-ray absorptiometry. Mean changes from baseline at 3 months and 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group.

  4. Number of Participants With at Least One Immunotherapy Treatment Delay

    Time frame: From baseline through 6 months

    The number and proportion of participants who experience at least one delay in scheduled immune checkpoint inhibitor treatment during the 6-month study period will be determined from clinical records and compared between the exercise and nutritional intervention group and the standard oncology care group.

  5. Number of Participants With Premature Discontinuation of Immune Checkpoint Inhibitor Treatment

    Time frame: From baseline through 6 months

    The number and proportion of participants who discontinue immune checkpoint inhibitor treatment before the planned completion of treatment during the 6-month study period will be determined from clinical records and compared between the exercise and nutritional intervention group and the standard oncology care group.

  6. Number of Participants With Grade 3 or Higher Immune Checkpoint Inhibitor-Related Toxicity

    Time frame: From baseline through 6 months

    The number and proportion of participants who experience at least one grade 3 or higher toxicity related to immune checkpoint inhibitor treatment during the 6-month study period will be determined from clinical records and compared between the exercise and nutritional intervention group and the standard oncology care group.

  7. Mean Change From Baseline in Phase Angle Assessed by Bioelectrical Impedance Analysis

    Time frame: Baseline, 3 months, and 6 months

    Phase angle will be measured in degrees using bioelectrical impedance analysis as an indicator of cellular integrity and muscle quality. Mean changes from baseline at 3 months and 6 months will be compared between the exercise and nutritional intervention group and the standard oncology care group.

Other outcomes

  1. Correlation Between Rectus Femoris Shear-Wave Velocity Assessed by 2D-SWE and Quadriceps Intramuscular Fat Fraction Assessed by MRI

    Time frame: Baseline

    Rectus femoris shear-wave velocity will be measured in meters per second (m/s) using two-dimensional shear-wave elastography (2D-SWE). Quadriceps intramuscular fat fraction will be assessed using chemical-shift magnetic resonance imaging (MRI) and reported as the MRI-derived intramuscular fat fraction. The relationship between the two measurements will be evaluated using Pearson's or Spearman's correlation coefficient, as appropriate according to the distribution of the data. The correlation coefficient is unitless and ranges from -1 to 1.

  2. Correlation Between Rectus Femoris Echogenicity Assessed by B-Mode Ultrasound and Quadriceps Intramuscular Fat Fraction Assessed by MRI

    Time frame: Baseline

    Rectus femoris echogenicity will be assessed from standardized B-mode ultrasound images as mean pixel intensity within a defined region of interest. At least three measurements will be averaged for the final value. Quadriceps intramuscular fat fraction will be assessed using chemical-shift magnetic resonance imaging (MRI) and reported as the MRI-derived intramuscular fat fraction. The relationship between the two measurements will be evaluated using Pearson's or Spearman's correlation coefficient, as appropriate according to the distribution of the data. The correlation coefficient is unitless and ranges from -1 to 1.

  3. Change From Baseline in Thigh Muscle Thickness Assessed by Ultrasound

    Time frame: Baseline, 3 months, and 6 months

    The thickness of the rectus femoris and vastus intermedius muscles will be assessed using ultrasound. Changes from baseline at 3 months and 6 months will be evaluated and compared with measures of lean mass obtained using dual-energy X-ray absorptiometry.

  4. Change From Baseline in Peripheral Blood NK and T-Lymphocyte Proportions

    Time frame: Baseline, 3 months, and 6 months

    The proportions of natural killer cells and T lymphocytes in peripheral blood will be assessed. Changes from baseline will be compared between the two study groups in the metastatic melanoma substudy population.

  5. Change From Baseline in Circulating Myokine Concentrations

    Time frame: Baseline, 3 months, and 6 months

    Circulating concentrations of selected myokines, including IL-6, IL-15, irisin/FNDC5, SPARC, and OSM, will be measured in peripheral blood. Changes from baseline will be compared between the exercise and nutritional intervention group and the standard oncology care group in the metastatic melanoma substudy population.

Study contacts

Contact information is provided by the study sponsor or research team.

Nada Rotovnik Kozjek, MD, PhD

CONTACT

[email protected]

+38641 612 541

Sponsors and collaborators

Lead sponsor

Institute of Oncology Ljubljana

Other

Collaborators

  • Science and Research Centre Koper

Registry information

Official study title

Effects of Randomized Controlled Exercise and Nutritional Interventions on Muscle Mass, Volume, Fat Infiltration, and Clinical Outcomes in Patients With Malignant Melanoma Receiving Immunotherapy

Acronym: MEL-FIT-IO

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Aug 12, 2026
Registry last updated
Aug 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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