High-Intensity Exercise and High-Fiber Diet for Immunotherapy Outcomes in Melanoma Patients: The DUO Trial

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

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)

Study Overview

• Status: Recruiting
• Conditions: Skin Cancer; Melanoma (Skin); Advanced Melanoma
• Intervention / Treatment: Behavioral: Exercise Program; Behavioral: Diet Program

Detailed 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 and American Association for Cancer Research.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dong-Woo Kang, PhD; Phone Number: 206-667-5188; Email: dkang@fredhutch.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Christina Dieli-Conwright, PhD
      • Contact: Christina Dieli-Conwright, PhD; Phone Number: 617-582-8321; Email: christinam_dieli-conwright@dfci.harvard.edu
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutch/University of Washington Cancer Consortium
      • Principal Investigator: Dong-Woo Kang, PhD
      • Contact: Dong-Woo Kang, PhD; Phone Number: 206-667-5188; Email: dkang@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Histologically diagnosed with melanoma.
• Having been or newly receiving immunotherapy for at least one month.
• Having a plan to continue immunotherapy for at least 8 weeks at the time of recruitment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2, indicating the ability to fulfill physical fitness and function assessments.
• Ability to understand and willingness to provide informed consent.

Exclusion Criteria:

• Participating in ≥ 150 minutes of moderate-to-vigorous aerobic exercise per week over the past month.
• Consuming ≥ 30 grams/day of dietary fiber over the past month.
• Having chronic medical conditions that are clinically unstable or uncontrolled with medications, deemed high-risk for exercise. These include but are not limited to unstable cardiac diseases, uncontrolled diabetes, and bone metastases with imminent risk of fracture.
• Having a high risk for noncompliance with study procedures. This will be determined by the study team based on the history of missed oncology appointments (i.e., ≥3 no-shows in 6 months) and poor responsiveness during recruitment (i.e., ≥3 unreturned contacts).
• Patients who are non-English speaking and cannot complete the participant surveys.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: High-Intensity Exercise (EX); 10 participants will complete: In-office baseline visit.; Virtual exercise sessions 3x weekly.; Post-intervention in-office visit.	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.
Experimental: Group B: High-Fiber Diet (DT); 10 participants will complete: In-office baseline visit.; 1x weekly appointment with research staff to review to review diet adherence.; Post-intervention in-office visit.	Behavioral: 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.
Experimental: Group C: Combined High-Intensity Exercise and High-fiber Diet (COMB); 10 participants will complete: In-office baseline visit.; Virtual exercise sessions 3x weekly.; 1x weekly appointment with research staff via Zoom platform to review to review diet adherence. Diet appointment may be combined with exercise session appointment.; Post-intervention in-office visit.	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.; Behavioral: 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.
No Intervention: Group D: Attention Control (AC); 10 participants will complete: In-office baseline visit.; Participants will receive a general healthy lifestyle guidebook.; Pot-intervention in-office visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Completing the Intervention Sessions	The primary outcome is feasibility and will be assessed by the proportion of participants completing the intervention sessions with >70% completion considered feasible.	Post-intervention (Week 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Change in Gut Microbiome Diversity	Gut microbiome diversity is 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)

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: American Association for Cancer Research; World Cancer Research Fund International
• Investigators: Principal Investigator: Dong-Woo Kang, PhD, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: March 1, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Skin Cancer; Melanoma; Advanced Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin and Connective Tissue Diseases; Melanoma; Skin Neoplasms; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: RG1125274; 20845 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No