Cancer Nutrition Study - A Study of Dietary Interventions in Cancer Patients Treated With Immune Checkpoint Inhibitors

Cancer Nutrition Study: CaNS - A Pilot Study of Dietary Interventions in Cancer Patients Treated With Immune Checkpoint Inhibitors

The goal of this clinical trial is to learn whether changing the diet can help improve gut health and support recovery from immune-related side effects caused by immune checkpoint inhibitor (ICI) cancer treatment in adults with solid tumors who develop moderate to severe immune-related side effects that require steroid treatment.

The main questions it aims to answer are:

Does a high-fermented food diet or a high-fiber resistant starch supplement change the gut microbiome (the bacteria and other microorganisms that live in the digestive tract) during treatment? Does either dietary approach improve gut microbiome diversity and function by the end of the 7-week intervention period?

Researchers will compare participants assigned to a high-fermented food diet with participants assigned to high-fiber resistant starch supplementation to see if one approach leads to greater improvements in the gut microbiome and related biological measures.

Participants will:

Be randomly assigned to 1 of 2 dietary intervention groups:

High-fermented food diet High-fiber resistant starch supplement Follow their assigned diet for 7 weeks, starting when their ICI treatment is restarted.

Provide stool samples before the intervention begins and regularly throughout the study.

Have blood samples collected at the start of the study and approximately every 3 to 4 weeks during participation.

Provide skin and mouth swab samples at the beginning of the study and again at Week 7.

Complete food diaries and symptom assessments during the study. Participate in a 2-week follow-up period after completing the dietary intervention.

Researchers will also evaluate the safety of the dietary interventions, whether immune-related side effects return, how the immune system responds, and how closely participants follow their assigned diet.

OBJECTIVES:

Primary:

1. To longitudinally assess changes in gut microbiota composition, diversity, and metabolomic function in patients with solid tumors who develop grade ≥2 irAEs during ICI therapy and undergo dietary modification with either high-fermented foods (Arm 1) or high-fiber supplementation (Arm 2).

Secondary:

1. To determine the safety and tolerability of dietary interventions in patients with ICI-related irAEs
2. To assess the incidence and severity of recurrent or new irAEs during and after dietary intervention
3. To characterize changes in circulating innate and adaptive immune cell populations (frequency, phenotype, and function) associated with dietary modification
4. To measure changes in circulating inflammatory cytokines and metabolites associated with dietary intervention

Exploratory:

1. To assess patient-reported gastrointestinal symptoms and quality of life during dietary intervention
2. To determine adherence rates to assigned dietary interventions using dietary logs and biomarker validation
3. To explore associations between baseline physical activity levels and gut microbiome composition
4. To longitudinally assess skin and oral microbiota composition, diversity, and function in relation to dietary modification
5. To perform integrative multi-omic analyses exploring relationships between diet, microbiome, immune phenotypes, and clinical outcomes

Inclusion Criteria:

• Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:

  1. Be willing and able to provide written informed consent.
  2. Adult ≥ 18 years of age, willing and able to provide blood and stool specimen and comply with dietary modification, as well as willing to fill out study required questionnaires (paper or electronic and web-based).
  3. Patients must have any type of electronic device such as a smartphone, tablet, or computer, etc. that can access the internet.
  4. Self-reported willingness to adhere with dietary intervention.
  5. Self-reported willingness to comply to scheduled follow ups, fill out questionnaires/food logs, provide stool samples and undergo venipuncture.
  6. Patients who are actively receiving ICIs and remain on this during the dietary intervention period (anti-PD-1/PD-L1, anti-CTLA4, anti-LAG3 or other immunotherapy that is currently FDA approved or listed in NCCN or ASCO guidelines for treatment of any solid malignancy, for example if patient is enrolled in clinical trial, studying pebrolizumab in any solid malignancy for new indication, these patients can be enrolled in this trial, given safety and efficacy of this ICI is well studied and approved in multiple settings) will be consented for the dietary intervention study.
  7. Any solid tumor (e.g., lung, melanoma, breast, head and neck, etc.) patients with grade ≥2 cutaneous (rash, dermatitis etc), constitutional (fatigue),rheumatological (arthralgia, arthritis) or GI (colitis, diarrhea, enteritis) irAEs while treated with ICIs i. Treated with topical steroids ii. Treated with systemic steroids or other immunemodulators iii. Are willing and able to continue ICIs concomitant with dietary intervention

Exclusion Criteria:

• An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Use of systemic antibiotics, antifungals, antivirals, or antiparasitics (intravenous, intramuscular, or oral) within the last 14 days

  2. Use of oral, intravenous, intramuscular, nasal, or inhaled 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:

     • Cytokines
     • Methotrexate or immunosuppressive cytotoxic agents, unless the regimen is deemed appropriate by the study investigator (e.g., use of low-dose hydroxychloroquine may be permitted at the investigator's discretion)
     • Regularly taking probiotics, fiber supplements, or any other medication or prebiotic dietary supplement that could affect the study outcome as determined by the principal investigator and unable/unwilling to discontinue for the study. These agents must be discontinued at least 14 days prior to the start of the diet

  3. Current use of chronic alcohol within the last 4 weeks, defined as more than five 1.5-ounce servings of 80-proof distilled spirits, five 12-ounce servings of beer, or five 5-ounce servings of wine per day

  4. Current consumption of fiber >30g (determined based on patient-reported intake or baseline questionnaire assessment [DHQ3 or ASA24]) or fermented food >3 portions a day (foods/drinks tested in the clinical trial: kefir, buttermilk, kimchi, sauerkraut, brine drinks, and kombucha)

  5. Any major bowel resection at any time. If patient had partial bowel resection ≥1 year ago, may be permitted at the investigator's discretion

  6. 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)

  7. Medical contraindications to intervention diet as determined by the treating physician

  8. Systemic antibiotics and proton pump inhibitors (PPIs) are not allowable during the study (should be discontinued >14 days prior). If PPIs or systemic antibiotics are initiated by the patient's treating physician, the patient should report this to the study team during the study period

     o Note: Administration of antibiotics for procedural purposes such as during wide local excision of a tumor, lymph node biopsy, or similar interventions will not be considered a protocol deviation but must be reported and documented

  9. Unable or unwilling to adhere to scheduled interventions and study procedures

  10. Patient with life-threatening irAEs including but not limited to myocarditis, encephalitis, or vasculitis

  11. History of active uncontrolled gastrointestinal disorders or diseases, including:

      • Inflammatory bowel disease (IBD), including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis
      • Malabsorption (e.g., active celiac disease)
      • Active persistent infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent), or Helicobacter pylori infection (untreated)