Overview
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.
Description
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.
Eligibility
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.
