This phase II trial tests how well a prebiotic food enriched diet targeting the gut microbiome in combination with ipilimumab and nivolumab work to treat patients with cutaneous melanoma that has not responded to previous treatment (refractory) with checkpoint blockade treatment, is stage III or IV and that cannot be removed by surgery (unresectable). The gut microbiome is the collection of microorganisms (like bacteria or fungi) that are present in the digestive system. Prebiotic food are foods typically high in fiber that contain nutrients to support the gut microbiome. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving a prebiotic food enriched diet with ipilimumab and nivolumab help improve the gut microbiome and general health of patients with melanoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06250335.
PRIMARY OBJECTIVE:
I. Determining the overall response rate (ORR) to prebiotic food-enriched diet (PreFED) intervention + ipilimumab/nivolumab (ipi/nivo) in immune checkpoint blockade (ICB)-refractory metastatic melanoma patients.
SECONDARY OBJECTIVES:
I. Determine progression-free survival (PFS) and overall survival (OS) to PreFED + Ipi/Nivo in ICB refractory melanoma.
II. Compliance and adherence to interventions.
III. Determine the safety (AEs) and tolerability (Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome [GSRS-IBS]) of the dietary intervention.
IV. Assess the rate of immune related adverse events in patients on immunotherapy receiving dietary interventions.
V. Assess the effects of dietary intervention on systemic and tumor immunity.
VI. Assess the effect of dietary intervention on gut microbiome composition and networks.
VII. Assess the effects of dietary intervention on gut metabolic output and systemic metabolism.
VIII. Assess the effects of dietary interventions on quality of life and other patient reported outcomes (PROs).
OUTLINE:
Patients receive 2-3 prebiotic snacks per day for 12 weeks and undergo diet counseling weekly for 12 weeks. Patients also receive standard of care ipilimumab intravenously (IV) and nivolumab IV every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who complete the initial 12-week PreFED intervention and are continuing with maintenance nivolumab will continue diet counseling alone for an additional 12 weeks. Patients undergo computed tomography (CT) scan or positron emission tomography (PET) scan and magnetic resonance imaging (MRI), blood sample collection and may undergo optional tumor biopsies throughout the study.
After completion of study treatment patients follow up at 12 weeks and then every 6 months for up to 2 years.
Trial PhasePhase II
Trial Typesupportive care
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorErez Nissim Baruch
