Clinical trial NCT04645680: Effect of Diet on the Immune System in Patients With Stage III-IV Melanoma Receiving Immunotherapy, DIET Study
Official title: Diet and Immune Effects Trial: DIET- A Randomized Double Blinded Dietary Intervention Study in Patients With Metastatic Melanoma Receiving Immunotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Clinical Stage III Cutaneous Melanoma AJCC v8
Clinical Stage IV Cutaneous Melanoma AJCC v8
Metastatic Melanoma
Pathologic Stage III Cutaneous Melanoma AJCC v8
Pathologic Stage IV Cutaneous Melanoma AJCC v8
Unresectable Melanoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-11-27
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Change in the gut microbiome
timeFrame: Baseline up to 11 weeks
Secondary outcomes:
measure: Change in systemic and tumor immunity
timeFrame: Up to 12 weeks
measure: Change in metabolic profile
timeFrame: Baseline up to 11 weeks
measure: Change in quality of life (QOL)
timeFrame: Baseline up to 11 weeks
measure: Incidence of adverse events
timeFrame: Up to 12 weeks
measure: Symptom profile
timeFrame: Up to 12-week follow-up
Other outcomes:
measure: Objective response rate (ORR) (unresectable cohort)
timeFrame: At 12-week follow-up
measure: Progression-free survival (PFS) (unresectable cohort)
timeFrame: Up to 12-week follow-up
measure: Recurrence rate (RR) (adjuvant cohort)
timeFrame: Up to 12-week follow-up
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jennifer McQuade
role: PRINCIPAL_INVESTIGATOR
References: