Previous research has shown that a higher fiber intake may have a beneficial effect on the intestinal health and improve the effectiveness of immunotherapy, but this is not certain. The objective of this double-blinded randomized clinical trial is to analyze, whether increased dietary fiber intake by patients with metastatic melanoma will increase the relative amount of Bifidobacterium, which in turn stimulates immune cell activity and improves the response to immunotherapy.
Histologically confirmed cutaneous melanoma classified as irresectable stage III or stage IV disease
Measurable disease according to RECIST 1.1 criteria
Age ≥ 18 years
Starting standard-of-care treatment with ICI in first line
Symptomatic brain metastases
Received prior immunotherapy; previous (neo)adjuvant treatment is allowed if the last administration is at least 6 months ago
Use of systemic immunosuppressive medications
Use of laxatives up to 1 week prior to start of ICI
Parallel
Dried chicory roots
Dietary supplementThe dried chicory roots are implemented using a dosage of 22.5 gram/day resulting in 18.5 gram additional fibers a day.
Placebo
Dietary supplementThe control arm will receive 12.4 grams of placebo a day, isocaloric to the intervention.
An increase in the relative abundance of Bifidobacterium in fecal samples.
The primary endpoint of this study is defined as a ≥5% (e.g. from 3% to 8%) increase in the relative abundance of Bifidobacterium in fecal samples between baseline (T0) and follow-up (T1) and significant differences between the experimental arm and the control arm.
Fecal microbiota composition
Study the baseline and on-treatment gut microbiota composition of patients with melanoma treated with ICI +/- additional dietary fiber.
Radiological response rate to ICI
Evaluate radiological response rates to ICI +/- additional dietary fiber, assessed by CT/PET scan per RECIST 1.1 defined as; the date of randomization to the date of disease progression or death, respectively.
Progression free survival (PFS)
Evaluate progression-free survival defined as; the date of randomization to the date of disease progression or death, respectively.
Overall survival (OS)
Evaluate overall survival to ICI +/- additional dietary fiber defined as; the date from randomization to date of death, respectively.
Habitual dietary intake (Food Frequency Questionnaire)
Nutritional intake is measured using a semi-quantitative Food Frequency Questionnaire (FFQ). Scores are calculated using the Dutch National Food Consumption tables. The FFQ will be used to evaluate habitual diet and fiber intake.
Physical activity level (Short QUestionnaire to ASsess Health-enhancing physical activity)
Physical activity is measured using the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH). The questions in the SQUASH are pre-structured in commuting, leisure time, household and work/school activities. Scores will be assigned to the different reported activities base on intensities in MET and translated to minutes of physical activity.
Sleep quality and duration (Pittsburgh Sleep Quality Index)
Sleep quality is measured with the Pittsburgh Sleep Quality Index (PSQI), a 19-item questionnaire with scores ranging from 0-21. A score above 5 indicates bad sleep quality.
Bristol Stool Scale (BSS)
Stool consistency is measured using the Bristol Stool Scale (BSS)
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Radboud University Medical Center
Lead sponsor
Wageningen University and Research
Collaborator
