Melanoma, Melanoma Advanced, Melanoma Metastatic, Melanoma (Skin Cancer), Melanoma (Skin) Stage IV
Conditions
Keywords
microbiota, gut microbiota, dietary fiber, life-style
Brief summary
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_SUPPLEMENTDried 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_SUPPLEMENTPlacebo
The control arm will receive 12.4 grams of placebo a day, isocaloric to the intervention.
Sponsors
Radboud University Medical Center
Wageningen University and Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
The FIGURE-IM is a randomized, double-blind, placebo-controlled, phase II clinical trial with two-arms to assess the effect of dietary fiber supplementation on the gut microbiota in patients with metastatic melanoma. Participants will be stratified based on gender and standard-of-care ICI treatment (nivolumab/pembrolizumab or nivolumab + ipilimumab). In the experimental arm the participants will receive fiber rich dried chicory roots additional to the habitual diet while receiving standard-of-care ICI treatment (nivolumab/pembrolizumab or nivolumab + ipilimumab). The participants from the placebo/control arm receive rice puffs which contain a neglectable amount of fiber while receiving standard-of-care ICI treatment (nivolumab/pembrolizumab or nivolumab + ipilimumab). Participants will be randomized 1:1.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| An increase in the relative abundance of Bifidobacterium in fecal samples. | From baseline (T0) to 3-4 weeks (T1) after start ICI | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fecal microbiota composition | Measurement at baseline (T0), 3-4 weeks (T1), 3-4 months (T2), and 6-7 months (T3) after start ICI | Study the baseline and on-treatment gut microbiota composition of patients with melanoma treated with ICI +/- additional dietary fiber. |
| Radiological response rate to ICI | 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. | 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) | 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. | Evaluate progression-free survival defined as; the date of randomization to the date of disease progression or death, respectively. |
| Overall survival (OS) | 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 overall survival to ICI +/- additional dietary fiber defined as; the date from randomization to date of death, respectively. |
| Evaluate the gastro-intestinal side effects of additional dietary fiber intake | From start intervention at baseline (T0) until the end of wash-out period at 6-7 months (T3) after start ICI. | Evaluate the gastro-intestinal side effects of additional dietary fiber intake, according to CTCAE common criteria v 5.0. |
Countries
Netherlands
Contacts
CONTACTKalijn Bol, dr.
CONTACTIsabel Ossekoppele, MS
Outcome results
None listed