Effect of Diet on the Immune System in Patients With Stage III-IV Melanoma Receiving Immunotherapy, DIET Study

Phase 2

Active, not recruiting

• Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Unresectable Melanoma; Clinical Stage IV Cutaneous Melanoma AJCC v8; Metastatic Melanoma
• Interventions: Other: Dietary Intervention; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

• Registration Number: NCT04645680
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

This phase II trial investigates the possible immune effects of two different diets targeting the gut microbiome in patients with stage III-IV melanoma that has been removed by surgery (resectable), has spread to other places in the body (metastatic), or is unable to be removed by surgery (unresectable), and who are being treated with the immunotherapy drugs pembrolizumab or nivolumab as part of their standard of care. Both diets are whole foods diets that meet the American Cancer Society recommendations for cancer patients, but they will vary in fiber content. The purpose of this trial is to learn about the effects of dietary interventions on the structure and function of the gut microbiome in patients with melanoma being treated with standard of care immunotherapy (pembrolizumab or nivolumab).

Detailed Description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

1. Assess the effects of dietary intervention on gut metabolic output and systemic metabolism.

2. Assess the effects of dietary intervention on systemic and tumor immunity

3. Determine the safety (AEs) and tolerability (GSRS-IBS) of the dietary intervention

4. Assess the rate of immune related adverse events in patients on immunotherapy receiving dietary interventions

5. Determine the maximum daily fiber content that 70% of participants are able to tolerate

6. 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)

7. Assess the effects of dietary interventions on quality of life and other patient reported outcomes (PROs)

EXPLORATORY OBJECTIVES:

1. 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).

2. 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.

Study Timeline

• Study Start: 2020-06-24
• Study First Submitted: 2020-10-16
• Study First Submitted QC: 2020-11-25
• Study First Posted: 2020-11-27
• Status Verified: 2024-06
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26
• Primary Completion: 2026-02-01
• Study Completion: 2026-02-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Age ≥ 18 years old.

2. Body mass index (BMI) 18.5-40 kg/m^2

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

4. English-speaking

5. Self-reported willingness to exclusively eat the provided diets

6. Self-reported willingness to comply with scheduled visits, undergo venipuncture, and provide stool samples

7. 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

Read More

Exclusion Criteria

1. History of >= grade II colitis or diarrhea on immunotherapy or any ongoing colitis or diarrhea of any grade
2. Unresolved >= grade III immune-related adverse event on immunotherapy (other than endocrinopathy requiring hormone replacement)
3. 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).
4. Medical contraindications to intervention diet as determined by the treating physician
5. Self-reported major dietary restrictions related to the intervention
6. Diagnosis of diabetes mellitus type I or type II that requires medical treatment or random glucose > 200 mg/dL
7. Antibiotic use within 21 days of planned start of equilibration diet (self-reported and/or noted by the treating physician)
8. 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
9. 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
10. Currently consuming an average estimated daily fiber intake exceeding 20 grams based on the results of the preliminary dietary assessment; vegetarian or vegan
11. Current smoker or heavy drinker (defined as > 14 drinks per week) or current self reported illicit drug use
12. Uncontrolled concurrent illness or infection or psychiatric illness/social situations that would limit compliance with study requirements
13. Unable or unwilling to undergo study procedures
14. Plan for travel during the study that would preclude adherence to prescribed diets
15. Cognitively impaired adults

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (isocaloric high-fiber diet)	Questionnaire Administration	Patients receive a whole foods diet that follows the recommended American Cancer Society guidelines but is higher in fiber for 11 weeks.
Arm I (isocaloric high-fiber diet)	Quality-of-Life Assessment	Patients receive a whole foods diet that follows the recommended American Cancer Society guidelines but is higher in fiber for 11 weeks.
Arm I (isocaloric high-fiber diet)	Dietary Intervention	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 diet)	Questionnaire Administration	Patients receive a standard whole foods diet recommended by the American Cancer Society for 11 weeks.
Arm II (isocaloric diet)	Dietary Intervention	Patients receive a standard whole foods diet recommended by the American Cancer Society for 11 weeks.
Arm II (isocaloric diet)	Quality-of-Life Assessment	Patients receive a standard whole foods diet recommended by the American Cancer Society for 11 weeks.

Primary Outcome Measures

Name	Time	Method
Change in the gut microbiome	Baseline up to 11 weeks	Changes of alpha-diversity (e.g., Shannon index) and abundance/relative abundance of different taxon levels (e.g., genus, family), from baseline to end of intervention, will be estimated. The outcomes will be compared. between two arms using t-test or Mann-Whitney test. Linear mixed effects models will be used for assessing the longitudinal data. Similarity in microbiome community structure will be assessed using principal coordinate analysis (PCoA) and compared using multivariate analysis of variance (MANOVA).

Secondary Outcome Measures

Name	Time	Method
Symptom profile	Up to 12-week follow-up	To assess gastrointestinal symptoms related to the dietary interventions, the GSRS-IBS will be used. The GSRS-IBS is a 13-item validated instrument with subscales for each item ranging from 0 ("no discomfort at all") to 7 ("very severe discomfort"). The gastrointestinal symptoms (GSRS-IBS) will be summarized using frequency counts and percentages.
Change in systemic and tumor immunity	Up to 12 weeks	Percent change in CD8 T cells using flow cytometry will be compared between two arms using t-test or Mann-Whitney test. Pearson or Spearman correlation coefficient will be used to assess the correlation between the outcome at baseline and end of intervention.
Change in metabolic profile	Baseline up to 11 weeks	Change in relative concentration (ion intensity determined as area under the curve) measured by mass spectrometry-based analysis of blood and fecal specimens from baseline to end of intervention will be compared between two arms using t-test or Mann-Whitney test.
Change in quality of life (QOL)	Baseline up to 11 weeks	Change in quality of life between baseline and end of intervention using a validated, 30 question scoring instrument (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Each question is scored in from 1 ("not at all") to 4 ("very much") in a Likert format. Linear mixed effects models will be used for assessing the longitudinal data. Pearson or Spearman correlation coefficient will be used to assess the correlation between measures for quality of life at baseline and end of intervention.
Incidence of adverse events	Up to 12 weeks	AEs attributed to diet as well as immune-related adverse events (irAEs) attributed to immunotherapy will be assessed using frequency counts and percentages.

Trial Locations

Locations (1)

M D Anderson Cancer Center; 🇺🇸 Houston, Texas, United States