Melanoma (Skin Cancer)
Conditions
Keywords
fasting, diet, fiber, high-fiber, melanoma, STF, short-term fasting, microbiome, checkpoint-inhibitor, checkpoint-inhibition, immunotherapy
Brief summary
The treatment of melanoma has improved significantly in recent years. A modern form of cancer treatment known as immunotherapy with checkpoint inhibitors plays a key role in this. These drugs help the immune system better recognize and fight cancer cells. Nevertheless, it remains a challenge to maximize treatment effectiveness while minimizing side effects. One possible approach to influencing treatment efficacy and tolerability is diet. A high-fiber diet, as recommended by the German Nutrition Society, increases the effectiveness of immunotherapy, in part through its influence on gut bacteria (the gut microbiota). Initial studies also show that short-term fasting (i.e., eating nothing or very little for a limited period) reduces the side effects of immunotherapy in mouse models and improves the tolerability of chemotherapy in humans. This study investigates the feasability of a study on short-term fasting, in addition to a high-fiber diet in patiens with melanoma undergoing immunotherapy. 40 participants will follow a high-fiber diet based on the recommendations of the German Nutrition Society. Additionally, half of the participants will undergo periodic cycles of short-term fasting of 72h with each immunotherapy. Another 20 participants will not undergo any intervention and serve as a control group. The goal is to determine whether this study concept is feasible. Exploratory outcomes include, quality of life, fatigue, tolerability of the therapy, impact on disease progression, immune system (flow cytometry) and gut bacteria (microbiome). The results are intended to help understand whether targeted dietary measures can support the effectiveness of modern cancer treatments.
Interventions
BEHAVIORALHigh-Fiber Diet
High-Fiber Diet (\>35g/day) according to the German Nutrition Society (Deutsche Gesellschaft für Ernährung, DGE) for 6 months.
BEHAVIORALHigh-Fiber Diet and Short-Term Fasting
High-Fiber Diet (\>35g/day) according to the German Nutrition Society (Deutsche Gesellschaft für Ernährung, DGE) and 72 hours of short-term fasting (max 400kcal/day) with every immunetherapy cycle for 6 months.
Sponsors
Charite University, Berlin, Germany
University Hospital Heidelberg
CHUM Microbiome Research Center Montréal
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed stage IIB-IIIC melanoma * Indication for immune checkpoint inhibition as monotherapy as determined by the tumor board * No prior systemic melanoma therapy * ECOG 0 or 1 * ≥ 18 years of age
Exclusion criteria
* Pregnancy or breastfeeding * Underweight (BMI ≤19.5) * Pre-existing eating disorder * Severe internal medical conditions (e.g., renal insufficiency with creatinine \> 2 mg/dL) or secondary malignancy * Current vegan diet or prolonged fasting (≤ 4 days) within the last 6 months * Use of antibiotics within 4 weeks prior to the start of the study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study feasability, measured by adequacy and efficiency of recruitment strategies | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Number of participants recruited per month (at least 2 per month) |
| Study feasability, measured by adherence to the intervention and dropout rate | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Adherence to the Intervention for intervention groups (at least 70% of the fasting cycles) |
| Study feasability, measured by acceptability of study outcome measures | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Patient acceptability of study assessments (number of completed study visits) |
| Feasibility of the study procedures | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Feasibility of study procedures, e.g. in terms of patient and provider acceptance of randomisation and outcome measures (percentage of eligible participants who explicitly refuse to participate because of the randomization process, missing item-level data, completion rates of questionnaires) |
| Feasibility of the intervention procedures | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Feasibility of the intervention methods (including patient acceptance of video and telephone consultations measured by no-show rate, patient safety in terms of number of adverse events) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Frequency and severity of treatment-emergent adverse events during the study |
| Hospitalizations rate | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Number of hospital admissions occurring during the study period |
| Dose Interruption or reduction | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Frequency of dose interruption or reduction |
| Cumulative dose | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Total cumulative dose of study treatment administered during the study period |
| Treatment discontinuation | After 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Frequency of treatment discontinuation and the reasons for it |
| Subjective Severity of the main symptom | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Patient-reported severity of the main symptom assessed using a Visual Analog Scale (VAS) ranging from 0 (no symptoms) to 100 (worst imaginable symptom severity) |
| Distress Thermometer | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Psychological distress assessed using the Distress Thermometer, a self-report scale ranging from 0 (no distress) to 10 (extreme distress). The DT is accompanied by a Problem list that identifies practical, family, emotional, spiritual/religious, and physical concerns |
| Health status (EQ-5D-5L) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Health status assessed using the EQ-5D-5L questionnaire. It evaluates five dimensions (mobilty, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated at five levels (no problems, slight problems, moderate problems, severe problems and extreme problems). |
| Short Form 36 | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Change in health-related quality of life assessed using the Short Form-36 (SF-36). The instrument evaluates eight domains of physical and mental health, with higher scores indicating better quality of life (scale 0-100). |
| Quality of life of cancer patients (EORTC QLQ-C30) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Quality of life of cancer patients assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). The instrument comprises 30 items evaluating global health status/quality of life, functional domains (physical, role, emotional, cognitive, and social functioning), and symptom domains. Higher scores on functional and global health status scales indicate better functioning and quality of life, whereas higher symptom scores indicate greater symptom burden. |
| Nutrition | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Dietary intake assessed using a 3-day food diary and using a validated Food Frequency Questionnaire (FFQ). The questionnaire evaluates the usual frequency of consumption of a range of food and beverage items over the specified recall period. Data are used to characterize dietary patterns and estimate intake of major food groups and nutrients. |
| Differential blood count | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Analysis of differential blood count to determine the distribution of leukocyte subtypes, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils." Unit of Measure: cells/µL |
| C-reactive protein (CRP) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | CRP (C-reactive protein) as a marker of inflammatory conditions is used to assess acute inflammation and monitor the effects of prolonged fasting and plant-based nutrition. Higher scores indicate more inflammation. Serum CRP, unit of Measure: CRP in milligram per liter (mg/L) |
| Alanine aminotransferase (ALT/ALAT) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Alanine aminotransferase (ALT/ALAT), Unit of Measure: U/L |
| Aspartate aminotransferase (AST/ASAT) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Aspartate aminotransferase (AST/ASAT), unit of Measure: U/L |
| Electrolytes | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | calcium in millimol per liter (mmol/L), potassium (mmol/L), sodium (mmol/L) |
| Creatinine | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Creatinine in µmol per liter (µmol/L), Biomarker of renal function and muscle metabolism |
| Glucose | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Glucose, unit of Measure: mg/dL oder mmol/L |
| Lactate dehydrogenase (LDH) | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | Lactate dehydrogenase (LDH), unit of Measure: U/L |
| S100 protein | Baseline, after 6 weeks, after 3 months, after 6 months, optional follow-ups at 12 and 18 months | S100 protein, unit of Measure: µg/L or ng/mL |
Countries
Germany
Contacts
CONTACTAnika Rajput, MD/PhD
CONTACTThomas Eigentler, Prof. Dr.
PRINCIPAL_INVESTIGATORAnika Rajput, MD/PhD
Charité - Universitätsmedizin Berlin, Department of Dermatology, Venerology and Allergology
Outcome results
None listed