Exercise and Diet Interventions During Immunotherapy in Melanoma Patients

Melanoma (Skin) Clinical Trial

Official title:

Modulating Immune-Microbiome Axis Through High-Intensity Exercise and High-Fiber Diet for Immunotherapy Outcomes in Melanoma Patients: The DUO Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06298734
• Other study ID #: 23-712
• Status: Not yet recruiting
• Phase: N/A
• Start date: July 2024
• Est. completion date: March 31, 2026

Study information

• Verified date: March 2024
• Source: Dana-Farber Cancer Institute
• Contact: Dong-Woo Kang, PhD
• Phone: 857-215-2229
• Email: Dong-Woo_Kang[@]dfci.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether high-intensity exercise and high-fiber diet are feasible and improve various health outcomes among participants with advanced melanoma receiving immunotherapy.

The names of the groups in this research study are:

• High-Intensity Exercise (EX)

• High-fiber Diet (DT)

• Combined High-Intensity Exercise and High-Fiber Diet (COMB)

• Attention Control (AC)

Description:

This single-center, four-arm, pilot randomized research study is to test if high-intensity exercise and high-fiber diet are feasible and effective in improving the gut microbiome health, immune function, physical fitness, treatment-related side effects, and treatment outcomes in participants with advanced melanoma receiving immunotherapy. Participants will be randomized into 1 of 4 study groups: Group A Exercise, Group B Diet, Group C Combined, and Group D Attention Control. Randomization means a participant will be placed into an intervention group by chance.

The information learned by doing this research may help determine whether participating in such lifestyle interventions are tolerable during immunotherapy and exert health benefits among melanoma participants.

The research study procedures include screening for eligibility, study visits, stool samples, blood tests, and questionnaires.

Participation in this study is expected to last up to a total of 9 weeks.

It is expected about 40 people will take part in this research study.

This study is sponsored by the World Cancer Research Fund International.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years; due to the rarity of the disease in those <18 years, this age bracket will not be included.

• Histologically diagnosed with advanced melanoma.

• Having been or newly receiving immune checkpoint inhibitor, including anti-PD1, antiCTLA4, and/or anti-LAG3 monoclonal antibodies, with palliative intent for at least one month with a plan to continue immunotherapy for at least 8 weeks (i.e., study intervention period) at the time of recruitment.

• Not receiving other concurrent tumor-directed systemic treatment (e.g., chemotherapy or targeted therapy).

• Medically cleared to participate in high-intensity exercise and high-fiber diet by their treating oncologist.

• Not having medical conditions that could exacerbate with exercise, such as bone disease at imminent risk of fracture or uncontrolled cardiopulmonary or metabolic diseases (e.g., uncontrolled hypertension or diabetes).

• Currently not meeting the physical activity guideline (i.e., more than 150 minutes per week of moderate-to-vigorous intensity, regular, structured aerobic exercise) over the past month at the time of recruitment.

• Currently not meeting the daily dietary fiber intake guideline (i.e., 30 grams/day) over the past month at the time of recruitment.

• Ability to communicate and complete written forms in English.

• Ability to understand and the willingness to sign informed consent prior to any study- related procedures.

• Willing to travel to DFCI for necessary data collection.

Exclusion Criteria:

• Receiving other concurrent systemic treatment for advanced melanoma such as chemotherapy or targeted therapy. This study is to exclusively target patients receiving immune checkpoint inhibitors where other treatments may impact the study outcomes of intervention efficacies and feasibilities.

• Participating in more than 150 minutes of moderate-to-vigorous aerobic exercise per week over the past month. This study targets insufficiently active persons to assess the effect of the described exercise intervention, where additional exercise done regularly will contaminate the intervention outcomes.

• Consuming more than 25 and 38 grams of dietary fiber per day for women and men, respectively over the past month. This study targets persons who insufficiently take dietary fiber to assess the effect of the described dietary intervention, where additional dietary fiber intake will contaminate the intervention outcomes.

• Having unstable comorbidities or medical conditions that prevent participation in high intensity exercise or high-fiber diet interventions. Patients with unstable medical conditions may develop unexpected adverse events from exercise and dietary changes. For the purpose of patients' safety, patients with unstable medical conditions are excluded.

• Subjects who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.

• Development of second malignancy (except for basal cell carcinoma or squamous cell carcinoma of the skin) that requires concurrent treatment, which would interfere with this study.

Related Conditions & MeSH terms

• Advanced Melanoma
• Melanoma
• Melanoma (Skin)
• Skin Cancer
• Skin Neoplasms

Intervention

Behavioral:
• Exercise Program
A high-intensity interval training, aerobic exercise program virtually supervised, home-based, and appointment-based program under direct one-on-one supervision by a trained oncology exercise specialist. Sessions will be conducted via the Zoom platform. Participants will be provided with home stationary bike, heart rate monitor, blood pressure monitor. For participants who do not have a smart device, a Wi-Fi enabled tablet will be provided.
• Diet Program
A virtual dietary consultation program supervised by trained research staff. Appointments will be conducted via the Zoom platform. Participants will receive an education handout at the baseline visit.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	World Cancer Research Fund International

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Gut Microbiome Diversity	The primary outcome of the study is the gut microbiome diversity measured by the Shannon Diversity Index. Alpha diversity of samples will be quantified using the Shannon diversity index, and beta diversity will be quantified using the Bray-Curtis dissimilarity.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Systemic Immune Function	Immune phenotyping will be conducted using the blood samples drawn at baseline and post-intervention. Immunofluorescence will be performed using a flow cytometry, which analyzes the physical and fluorescent properties of cells in suspension in real-time as they flow through the instrument.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Cardiopulmonary Fitness	Cardiorespiratory fitness will be assessed as VO2peak by a graded maximal cycle exercise stress test. VO2peak is defined as the highest values of oxygen uptake averaged among every 15-second interval during the test.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Short Physical Performance Battery (SPPB)	Physical function will be assessed by the SPPB. This includes the following 3 lower extremity measures completed in the following order. Timed balance (seconds): Balance will be assessed under 3 conditions (side-by-side, semi-tandem, and tandem stands). Gait speed (seconds): Gait speed will be assessed over a 4-meter flat surface distance. The participant will be asked to complete 2 attempts of this test. Time will be recorded using an electronic timing system. Chair stand (seconds): Chair stand will be performed under 2 conditions: a) subjects will perform a single chair stand; b) subjects will be asked to perform 5 repeated chair stands as quickly as possible; time to completion will be recorded.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Percent Body Fat	Percent body fat will be assessed via bioelectrical impedance using a validated device (Tanita 780, Arlington Heights, IL). Participants will be asked to remove their shoes and socks and stand still on the device while holding the handles with their hands at their sides. The device will estimate body fat using an algorithm based on age, sex, height, and body weight.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Lean mass	Lean mass (kg) will be assessed via bioelectrical impedance using a validated device (Tanita 780, Arlington Heights, IL). Participants will be asked to remove their shoes and socks and stand still on the device while holding the handles with their hands at their sides. The device will estimate body fat using an algorithm based on age, sex, height, and body weight.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Hip circumference	A constant-tension tape measure will be used to obtain waist circumference (i.e., the distance around the waist using the umbilicus as the reference point) (cm).	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Waist circumference	A constant-tension tape measure will be used to obtain hip circumference (the distance around the widest girth of the buttocks using the greater trochanter as a landmark) (cm).	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Health-Related Quality of life (EORTC-QLQ C30)	The European Organization for Research and Treatment of Cancer- Quality of Life Questionnaire-C30 will assess health-related quality of life, consisting of subscales including functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures. The score ranges from 0 to 100 and a higher value indicates a better quality of life.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in MDASI-Immunotherapy Questionnaire Score	MD Anderson Symptom Inventory-Immunotherapy (MDASI-Immunotherapy EPT) module is comprised of 20 symptoms including 7 immunotherapy-specific items in addition to the 13 MDASI core symptoms.The MDASI asks participants to rate the severity of disease-related and treatment-related symptoms during the past 24 h. Each symptom (pain, fatigue, nausea, disturbed sleep, emotional distress, shortness of breath, difficulty remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling, rash, diarrhea, pain the abdomen, swelling in the hands and legs, headache, night sweats and fever and/or chills) is rated on an 11-point scale ranging from 0 (not present) to 10 (as bad as you can imagine). The MDASI-Immunotherapy EPT has been shown to be valid and reliable.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Anxiety (HADS)	The Hospital Anxiety and Depression Scale (HADS) is a 14-question instrument that measures anxiety and depression with seven questions for each. Each question is scored between zero (no impairment) and three (severe impairment), with a maximum score of 21 for anxiety.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Depression (HADS)	The Hospital Anxiety and Depression Scale (HADS) is a 14-question instrument that measures anxiety and depression with seven questions for each. Each question is scored between zero (no impairment) and three (severe impairment), with a maximum score of 21 for depression.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Change in Sleep Quality (PSQI)	The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. The PSQI contains 19 self-rated questions and 5 questions rated by the bed partner or roommate (if one is available). Only self-rated questions are included in the scoring. The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points. The seven components are then summed to obtain a global score ranging from 0-21 points.	Baseline (Week 1) and post-intervention (Week 10)
Secondary	Proportion of Participants Completing the Exercise Intervention Sessions	The primary outcome is feasibility and will be assessed by the proportion of participants completing the exercise intervention sessions with >70% completion considered feasible.	Post-intervention (Week 10)