Dietary Fiber to Induce Gut Microbiota-mediated Response to Immunotherapy in Melanoma.

Overview

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.

Interventions

• Dietary supplement Dried chicory roots
  The dried chicory roots are implemented using a dosage of 22.5 gram/day resulting in 18.5 gram additional fibers a day.
• Dietary supplement Placebo
  The control arm will receive 12.4 grams of placebo a day, isocaloric to the intervention.

Primary outcome measures

• An increase in the relative abundance of Bifidobacterium in fecal samples. [Time frame: From baseline (T0) to 3-4 weeks (T1) after start ICI]

Secondary outcome measures (5)

• Fecal microbiota composition [Time frame: Measurement at baseline (T0), 3-4 weeks (T1), 3-4 months (T2), and 6-7 months (T3) after start ICI]
• Radiological response rate to ICI [Time frame: From baseline (T0) to the first date of documented progression or date of death from any cause, wichever came first, assesed up to 5 year.]
• Progression free survival (PFS) [Time frame: From baseline (T0) to the first date of documented progression or date of death from any cause, wichever came first, assesed up to 5 year.]
• Overall survival (OS) [Time frame: From baseline (T0) on, survival follow-up will be continued after study completion for a maximal of 5 years in accordance with standard-of-care follow-up.]
• Evaluate the gastro-intestinal side effects of additional dietary fiber intake [Time frame: From start intervention at baseline (T0) until the end of wash-out period at 6-7 months (T3) after start ICI.]

Eligibility criteria

Inclusion criteria

• 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
• Written informed consent must be given
• Able to read and understand Dutch or English
• Able to comply with study procedures (e.g. willing to provide fecal samples)

Exclusion criteria

• 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
• Use of supplements that alter bowel function or gut microbiota such as fibers/prebiotics, probiotics, synbiotics, or postbiotics up to 1 month prior to start of ICI
• Use of antibiotics up to 1 months prior to start of ICI
• Use of proton pumps inhibitors (PPI's) up to 3 months prior to start of ICI
• Pregnant or lactating
• Current participation in another clinical trial requiring the use of study medication
• Has a known allergy to plants such as lettuce, sage, tarragon, chicory, artichoke, chamomile, daisy, or sunflower.
• Has a medical history of gastrointestinal resection (appendectomy is allowed)
• Has active inflammatory bowel disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Netherlands · 2 centers

• Medical Oncology — Nijmegen
• Universitair Medisch Centrum Groningen — Groningen

Identifiers

NCT: NCT07686835 · R0007807A

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗