Diet and Immune Effects Trial: DIET- A Randomized Double Blinded Dietary Intervention Study in Patients With Metastatic Melanoma Receiving Immunotherapy

PRIMARY OBJECTIVE:

To establish the effects of dietary intervention on the structure and function of the gut microbiome.

SECONDARY OBJECTIVES:

• Assess the effects of dietary intervention on gut metabolic output and systemic metabolism.
• Assess the effects of dietary intervention on systemic and tumor immunity
• Determine the safety (AEs) and tolerability (GSRS-IBS) of the dietary intervention
• Assess the rate of immune related adverse events in patients on immunotherapy receiving dietary interventions
• Determine the maximum daily fiber content that 70% of participants are able to tolerate
• Assess the adherence to the dietary interventions as defined by 70% of calories consumed over the duration of the study being derived from provided diets (as measured by food records)
• Assess the effects of dietary interventions on quality of life and other patient reported outcomes (PROs)

EXPLORATORY OBJECTIVES:

• Assess the association of dietary interventions with clinical outcomes (objective response rate [ORR] and progression-free survival [PFS] rate in unresectable cohort and recurrence rate [RR] in adjuvant cohort).
• Explore predictors of biological response to dietary interventions.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (ISOCALORIC HIGH-FIBER DIET): Patients receive a whole foods diet that follows the recommended American Cancer Society guidelines but is higher in fiber for 11 weeks.

ARM II (ISOCALORIC CONTROL DIET): Patients receive a standard whole foods diet of recommended by the American Cancer Society for 11 weeks.

After completion of study, patients are followed up at 12 weeks.

Inclusion criteria

• Age ≥ 18 years old.
• Body mass index (BMI) 18.5-40 kg/m^2
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• English-speaking
• Self-reported willingness to exclusively eat the provided diets
• Self-reported willingness to comply with scheduled visits, undergo venipuncture, and provide stool samples
• Cohort-specific:

• 1 Adjuvant Melanoma: i. Resected Stage II-IV melanoma with planned initiation of adjuvant anti-PD1 +/- anti-CTLA4 or anti-LAG3
• 2 Unresectable Melanoma: i. Histologically confirmed unresectable stage III or Stage IV melanoma with planned initiation of standard of care anti-PD1 +/- CTLA4 or anti-PD1 +/- LAG3 immunotherapy and no prior immunotherapy in the metastatic setting.
• 3 Neoadjuvant Melanoma: i. Histologically confirmed stage III/IV melanoma with planned initiation of neoadjuvant anti-PD1 +/- anti-CTLA4 or anti-LAG3 1. Participants must have archival tissue block available or be willing to undergo a newly-obtained core needle or incisional biopsy at baseline. Fine needle aspiration is not acceptable.
• 4 Unresectable RCC: i. Unresectable clear-cell renal cell carcinoma with planned initiation of standard of care anti-PD1 +/- anti-CTLA4 immunotherapy

Exclusion criteria

• History of >= grade II colitis or diarrhea on immunotherapy or any ongoing colitis or diarrhea of any grade
• Unresolved >= grade III immune-related adverse event on immunotherapy (other than endocrinopathy requiring hormone replacement)
• History of active inflammatory bowel disease or major gastrointestinal surgery (not including appendectomy or cholecystectomy) within 3 months of enrollment or any history of total colectomy, or bariatric surgery (bariatric surgery which does not disrupt the gastrointestinal lumen, i.e. restrictive procedures such as banding, are permitted).
• Medical contraindications to intervention diet as determined by the treating physician
• Self-reported major dietary restrictions related to the intervention
• Diagnosis of diabetes mellitus type I or type II that requires medical treatment or random glucose > 200 mg/dL
• Antibiotic use within 21 days of planned start of equilibration diet (self-reported and/or noted by the treating physician)
• Has a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study intervention administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Regularly taking probiotics, fiber supplements, or any other medication or supplement that could affect study outcome as determined by the principal investigator and unable/unwilling to discontinue for the purpose of the study. These agents must be discontinued at least 14 days prior to start of diet
• Currently consuming an average estimated daily fiber intake exceeding 20 grams based on the results of the preliminary dietary assessment; vegetarian or vegan
• Current smoker or heavy drinker (defined as > 14 drinks per week) or current self reported illicit drug use
• Uncontrolled concurrent illness or infection or psychiatric illness/social situations that would limit compliance with study requirements
• Unable or unwilling to undergo study procedures
• Plan for travel during the study that would preclude adherence to prescribed diets
• Cognitively impaired adults