Promoting Response to IMmunotherapy by Exercise in Patients With Advanced Renal Cell Carcinoma

NCT07680556 | Recruiting

• 1 other identifier: NL-011443
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

The primary aim of this study is to evaluate the feasibility of a supervised high intensity interval training (HIIT) program during first-line dual immune checkpoint inhibitor (ICI) therapy (nivolumab plus ipilimumab) in patients with advanced renal cell carcinoma (RCC). The second aim is to generate preliminary data on the effects of exercise on the immune cell phenotype and function, gut microbiota composition, physical fitness, patient-reported outcomes and clinical outcomes. This is a two-arm randomized controlled pilot trial in which 30 patients with advanced RCC scheduled to receive first-line nivolumab plus ipilimumab will be randomized in 1:1 ratio to an exercise intervention group or usual care group. The exercise intervention consists of two 60-minute supervised HIIT sessions per week, delivered by oncology-trained physiotherapists and one additional home-based moderate-intensity aerobic exercise sessions per week. The intervention starts with the first cycle of immunotherapy and continues for four treatment cycles. Participants in both groups will receive usual care and general exercise guidelines. Measurements include blood and stool sampling for microbiome and immune parameters analysis, physical fitness assessments, physical fitness monitoring, body composition measurements, and patient-reported outcomes related to quality of life, fatigue, depression, sleep and diet.

Conditions

Oncology

Keywords

Oncology; Exercise; immunotherapy; Renal cell carcinoma; immune-related adverse events; randomized controlled trial; immune function

Outcome Measures

Primary Outcomes (3)

• Participation rate

  Calculated by the proportion of eligible patients that participate. An accrual rate lower than 20% will be defined as not feasible.

  Study enrolment period (approximately 24 months)

• Exercise intervention adherence

  Adherence will be assesed by attendance and exercise relative dose intensity (ExRDI). Attendence will be assessed by dividing the number of attended sessions by the number of prescribed sessions. ExRDI will be calculated as the percentage of the exercise intensity achieved during the performed sessions relative to the total prescribed exercise intensity expressed as a percentage. The information will be collected using questionnaires and exercise-logs registered by the physical therapists. These logs will be collected by the researcher

  12 weeks (during intervention period)

• Immune-related and exercise-related adverse events

  Immune related adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 based on medical records and the patient reported outcomes (PRO)-CTCAE completed by patients before each immunotherapy cycle and at 3-month follow up.

  24 weeks (during intervention period of 12 weeks, and 12 weeks post intervention)

Secondary Outcomes (12)

• Body composition

  12 weeks (Baseline, post-intervention)

• Estimated aerobic fitness

  12 weeks (Baseline, post-intervention)

• Lower body muscle function

  12 weeks (Baseline, post-intervention)

• Physical activity

  12 weeks (Baseline, post-intervention)

• Health-related quality of life (HRQoL)

  12 weeks (Baseline, post-intervention)

Study Arms (2)

High Intensity Interval Training (HIIT)

EXPERIMENTAL

High intensity aerobic interval training during dual immunotherapy

Behavioral: HIIT

Usual care control (UC)

NO INTERVENTION

The control group will receive usual care and will be receive a folder about physical activity recommendations.

Interventions

HIIT BEHAVIORAL

The intervention group will be offered a supervised exercise program consisting of two 60-minute sessions per week, including continuous aerobic exercise and HIIT. Sessions will be supervised by physiotherapists specialized in oncology, and the training load will be tailored to a patient's individual fitness levels throughout the intervention. Following a short warm-up, participants will perform repeated high-intensity cycling intervals targeting 85-95% of their estimated peak heart rate corresponding to a Borg Rating of Perceived Exertion (RPE) 16-18), interspersed with periods of active recovery at light intensity. The HIIT component will be followed by moderate-intensity aerobic exercise at approximately 70% of the estimated heart rate (Borg RPE 13-14), and a cool-down period. In addition, participants will be asked to be physically active for at least 30 minutes at moderate intensity, in accordance with the American College of Sports Medicine (ACSM) guidelines.

High Intensity Interval Training (HIIT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• Diagnosed with advanced RCC with indication for standard-of-care dual ICI treatment.
• Able and willing to give written informed consent.

You may not qualify if:

• Life expectancy \<6 months.
• Unable to perform basic activities of daily living such as walking.
• Presence of cognitive impairment or severe emotional instability (e.g. schizophrenia, Alzheimer's disease, alcohol addiction), at the discretion of the investigator.
• Presence of other disabling comorbidities that may interfere with the ability to perform physical exercise (e.g., heart failure, chronic obstructive pulmonary disease (COPD, GOLD stage 3 or 4), orthopaedic conditions, or neurological disorders such as hernia, paresis, amputation or active rheumatoid arthritis), at the discretion of the investigator.
• Current participation in structured vigorous aerobic and/or resistance exercise ≥ 2 times per week at a level comparable to the intervention

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (2)

Rijnstate

Arnhem, Gelderland, Netherlands

RECRUITING

Radboudumc

Nijmegen, Gelderland, Netherlands

RECRUITING

MeSH Terms

Conditions

Neoplasms; Motor Activity; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Behavior; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Laurien M Buffart, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Sasja F Mulder, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Theo van Voorthuizen, MD

  Rijnstate

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laurien Buffart, PhD

CONTACT

+31 24 3667310; laurien.buffart@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: July 2, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: July 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR

Locations

NL (2)