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

Phase 2RecruitingNCT07686835

Radboud University Medical Center70 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Melanoma (Skin) Stage IV Melanoma (Skin Cancer)Melanoma Metastatic Melanoma Advanced Melanoma

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: From baseline (T0) to 3-4 weeks (T1) after start ICI

Secondary Outcomes

Fecal microbiota composition

Study the baseline and on-treatment gut microbiota composition of patients with melanoma treated with ICI +/- additional dietary fiber.

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

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.

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)

Evaluate progression-free survival defined as; the date of randomization to the date of disease progression or death, respectively.

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)

Evaluate overall survival to ICI +/- additional dietary fiber defined as; the date from randomization to date of death, respectively.

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

Evaluate the gastro-intestinal side effects of additional dietary fiber intake, according to CTCAE common criteria v 5.0.

Time frame: From start intervention at baseline (T0) until the end of wash-out period at 6-7 months (T3) after start ICI.