The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT04866810

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

The gut microbiome is made up microorganisms. These include the good and bad bacteria that live in the digestive tract. Changes in the gut microbiome have been linked to the development of cancer. Researchers want to learn more about the effects of modulating the microbiome with diet and exercise.

Objective:

To see if nutritional intake and physical activity change the gut microbiome in people with melanoma.

Eligibility:

Adults age 18 and older with previously untreated melanoma who will be getting immunotherapy treatment for their disease.

Design:

Participants will not have visits at NIH. They will have phone calls or videocalls.

Participants will be screened with a medical history and medical record review.

Participants will give stool samples. They will fill out surveys about their health, feelings, diet, and exercise.

Participants will be put in 1 of 2 groups. They will follow their group s plan for 4 months. They will be contacted throughout the study.

Intervention Group participants will follow a plant-based, high-fiber diet. They will do at least 150 minutes of moderate or 75 minutes of high-intensity exercise per week. They will have sessions with psychology staff to help them make positive lifestyle changes.

Control Group participants will be taught healthy eating and exercise guidelines. But they will not be asked to change their diet or exercise habits.

All participants will record what they eat in the MyFitnessPal app. They will get a scale to measure their weight each week. They will wear a Garmin(R) physical activity tracker at all times. They can take the tracker off to bathe or shower.

Participation will last for 6 months....

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Behavioral: Intervention Arm Behavioral: Control	N/A

Detailed Description

Background:

The human gut microbiome is a topic of growing research interest because it modulates many systems, including immune function; and, alterations of the microbiome have been associated with the development of many diseases, including cancer.

Optimization of the gut microbiome can increase the probability of responding to immune checkpoint inhibitor therapy with responders exhibiting a higher level of gut microbial diversity than non-responders. Therefore, efforts are underway to investigate the effects of modulating the microbiome on response to immune checkpoint inhibitor therapy.

Diet is a major modulator of the gut microbiome. In particular, a high-fiber, plant-based diet promotes greater gut microbial diversity while diets high in animal fats and protein are associated with lower gut microbial diversity.

Exercise has been shown to increase gut microbial diversity independent of diet in both mice and humans. In addition, exercise has long been known to lower cancer risk and improve outcomes in cancer patients, possibly through its ability to enhance immune function.

Although diet and exercise prescriptions are cost-effective and implementable on a large scale, poor compliance is a major issue. Acceptance and Commitment Training (ACT) can help improve participant engagement and compliance with lifestyle change recommendations.

In previously untreated, unresectable melanoma participants, we hypothesize that the combination of a high-fiber, plant-based diet and exercise will increase gut microbial diversity and potentially increase the probability of responding to immune checkpoint inhibitor therapy.

Objectives:

To determine the feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in previously untreated, unresectable melanoma participants who will be undergoing treatment with relatlimab and nivolumab.

Eligibility:

Adults with previously untreated and unresectable melanoma who will be undergoing treatment with relatlimab and nivolumab.

Adequate organ function as defined by the liver, kidney, and hematologic laboratory testing.

Participants who have recently used antibiotics, probiotics, fiber supplements, or any other products/medications that can significantly alter the gut microbiome will be excluded.

Design:

Feasibility trial wherein participants will be randomized in a 1-to-1 fashion to the following arms:

Intervention Arm: 30 participants will be instructed to adopt a high-fiber, plant-based diet and to engage in at least 150 minutes of moderate or 75 minutes of vigorous intensity exercise per week.

Control Arm: 30 participants will be educated on general healthy eating and exercise guidelines, but they will not be instructed to change their behavior.

All participants will be asked to periodically record dietary intake (in the MyFitnessPal app or other logs, if needed), to wear a Garmin (trademark) physical activity tracker, and to collect stool samples periodically. Feasibility will be determined by assessing whether greater than or equal to 60% of participants in each arm adhere to their respective protocols.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

The Effect of Diet and Exercise on ImmuNotherapy and the Microbiome (EDEN)

Anticipated Study Start Date :

Aug 30, 2022

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Oct 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Intervention	Behavioral: Intervention Arm High fiber, plant based diet + exercise prescription with ACT sessions
Other: 2 Control- Standard diet and Exercise	Behavioral: Control Standard diet and exercise recommendations

Arm

Intervention/Treatment

Experimental: 1

Intervention

Behavioral: Intervention Arm

High fiber, plant based diet + exercise prescription with ACT sessions

Other: 2

Control- Standard diet and Exercise

Behavioral: Control

Standard diet and exercise recommendations

Outcome Measures

Primary Outcome Measures

feasibility of conducting a decentralized clinical trial involving diet and exercise prescriptions with stool sample collections in patients receiving anti-PD1/PDL1 monotherapy [43 days]
Assessing compliance with study requirements (e.g., logging diet, physical activity per the fitness tracker, completing PROs), assessed per arm; 60% compliance is a success

Secondary Outcome Measures

Progression Free Survival (PFS) [through day 113]
PFS will be evaluated on the two arms using a Kaplan-Meir curve and compared using a log-rank test.
Quality of Life (QOL) [baseline, day 43 and day 113]
QOL factors in the PRO surveys will be measured using T-scores and T-tests or ANOVA.
Objective Response Rate (ORR) [through day 113]
Response rates will be compared using a one-tailed Fisher's exact test to determine if the response rate exhibits a trend toward improvement with lifestyle intervention

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:
Participants must have histologically or cytologically confirmed unresectable melanoma that has not been treated with any systemic therapy.
Participants must be planning to undergo treatment with the combination of relatlimab and nivolumab immunotherapy. Note: This treatment is permissible to have started up to 14 days prior to completion of baseline assessments on this study to still be eligible for

enrollment.

Participants must have measurable disease, per RECIST 1.1.
Age greater than or equal to 18 years and English speaking. English-language ability is required because a portion of the study involves reading and responding to English-language questionnaires, along with creating a free response spoken answer to a question, where the information will be transcribed and analyzed.
Willingness and capability to comply with diet and exercise prescriptions, use the MyFitnessPal app, wear the Garmin (trademark) device, complete surveys, and provide stool samples. Participants must own a smartphone capable of running the MyFitnessPal and

Garmin Connect (trademark) apps.

ECOG performance status <2 (Karnofsky >60%,).
BMI 18.5 -35 kg/m2
The ability of the subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Participants who are receiving any other investigational agents.
Any concurrent malignancy that requires active systemic therapy
Any health condition that requires treatment with cytotoxic chemotherapy or targeted therapy
Medical contraindications to the study diet and/or exercise prescriptions as determined by a physician
Self-reported dietary and/or exercise restrictions that would preclude adherence to the study diet and exercise prescriptions
Systemic antibiotic use within the past 30 days
Use of probiotic supplements (probiotic foods such as yogurt, kefir, sauerkraut, etc., are permissible), fiber supplements, bile acid sequestrants, weight loss supplements, or appetite suppressants within the last 30 days.
Women known to be pregnant or lactating are excluded from the study because it is unknown if the study diet and exercise prescriptions may have deleterious effects on the child and/or mother in the context of pregnancy/breastfeeding.
Current smoker or < 8 weeks since smoking cessation. There is evidence that smoking may alter the microbiome.
Heavy drinker defined as >14 alcoholic drinks per week
Current illicit drug use. There is evidence that illicit drug use may alter the microbiome.
Diagnosis of diabetes mellitus type I or II that requires treatment
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.