Melanoma
Conditions
Keywords
Immune Checkpoint Inhibitors, Resistance Exercise, Nutritional Intervention, Skeletal Muscle Mass, Muscle Quality, Sarcopenia
Brief summary
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.
Detailed 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.
Interventions
BEHAVIORALStructured Resistance Exercise
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.
BEHAVIORALIndividualized Nutritional Support
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.
Sponsors
Institute of Oncology Ljubljana
Science and Research Centre Koper
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sarcopenia at 6 Months | 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. |
| Change From Baseline in Thigh Skeletal Muscle Volume Assessed by Magnetic Resonance Imaging | 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. |
| Change From Baseline in Skeletal Muscle Fat Infiltration Assessed by Magnetic Resonance Imaging | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lean Body Mass Assessed by Dual-Energy X-Ray Absorptiometry | 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. |
| Mean Change From Baseline in Total Body Fat Mass Assessed by Dual-Energy X-Ray Absorptiometry | 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. |
| Number of Participants With at Least One Immunotherapy Treatment Delay | 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. |
| Number of Participants With Grade 3 or Higher Immune Checkpoint Inhibitor-Related Toxicity | 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. |
| Number of Participants With Premature Discontinuation of Immune Checkpoint Inhibitor Treatment | 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. |
| Mean Change From Baseline in Phase Angle Assessed by Bioelectrical Impedance Analysis | 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. |
| Mean Change From Baseline in Resting Energy Expenditure Assessed by Indirect Calorimetry | 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. |
Countries
Slovenia
Contacts
CONTACTNada Rotovnik Kozjek, MD, PhD
PRINCIPAL_INVESTIGATORNada Rotovnik Kozjek
Institute of Oncology Ljubljana
Outcome results
None listed