Exercise Prehabilitation in Patients With Head and Neck Squamous-cell Carcinoma: The FIT4TREAT Trial

Study Overview
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Brief Summary
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The main purpose of this randomized-controlled trial is to evaluate the effects of prehabilitation based on exercise training (ET) on functional capacity in HNC patients treated with chemoradiotherapy (CRT). Forty-six participants will be randomized (1:1 ratio) into prehabilitation and usual care groups. The length of intervention will be at least 2 weeks. Data will be collected at diagnosis, immediately before anti-cancer treatment start and 4 weeks following CRT. Primary outcome is functional capacity as assessed by the six-minute walk test. Additional measures include muscle strength, endothelial function, arterial stiffness, inflammatory biomarkers, body composition, quality of life, treatment tolerance, compliance to treatment, progression-free survival, and overall survival.

Official Title
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Exercise Prehabilitation in Patients With Head and Neck Squamous-cell Carcinoma: The FIT4TREAT Trial

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Other: Prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old; Histologically confirmed HNSCC located on the oral cavity, larynx, oropharynx, hypopharynx, nasopharynx or in lymph nodes from an unknown primary tumor (stage I-IV); Proposed for concomitant chemoradiotherapy with curative intent; Date of treatment beginning ≥2 weeks from baseline assessment; ECOG-Performance Status 0-1. Exclusion Criteria: Completion of previous anticancer treatment within less than a year; Uncontrolled hypertension, cardiac or pulmonary disease; Contraindications to exercise training; Inability to provide informed consent; Expected inability to fulfil the proposed schedule.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prehabilitation Group<br>In addition to standard medical care, the prehabilitation group will have three supervised exercise training sessions per week from diagnosis to start of radiotherapy (pre-treatment phase). | Other: Prehabilitation<br>* In addition to usual care, the prehabilitation group will exercise 3 times a week, starting immediately after diagnosis and throughout the pre-treatment period. Each exercise session will encompass 5-min warm-up and 45-min conditioning exercises. Aerobic training will be performed using low-volume high intensity interval training (HIIT). The HIIT duration is 16-20 minutes and it will be performed with 8-10 intervals of high intensity (1 minute) and 8-10 intervals of low intensity (1 minute). High intensity intervals will be set to an external load that represents 85-90% of estimated VO2Peak. In addition, patients will do resistance training at moderate intensity. Patients will complete 2 sets of 12 repetitions of 5 upper and lower body exercises.<br>|
| No Intervention: Control Group<br>The control group will receive the standard medical care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Capacity | Assessed by six-minute walk test. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Capacity | Assessed by six-minute walk test. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Isometric Handgrip Muscle Strength | Assessed by hand dynamometer. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Isometric Handgrip Muscle Strength | Assessed by hand dynamometer. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Arterial Stiffness | Assessed by carotid-femoral pulse wave velocity. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Arterial Stiffness | Assessed by carotid-femoral pulse wave velocity. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Endothelial Function | Assessed by brachial artery dilation to endothelial-dependent stimuli using an ultrasound, according to the recommendations. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Endothelial Function | Assessed by brachial artery dilation to endothelial-dependent stimuli using an ultrasound, according to the recommendations. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Lower Limb Functionality | Assessed by 30-second sit to stand test. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Lower Limb Functionality | Assessed by 30-second sit to stand test. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Health-related Quality of Life | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). This is a patient-reported questionnaire composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status / QoL scale, and 6 single items. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Health-related Quality of Life | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). This is a patient-reported questionnaire composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status / QoL scale, and 6 single items. All of the scales and single-item measures range in score from 0 to 100. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Head and Neck Cancer-specific Quality of Life | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43). This is the head and neck cancer specific module that contains 43 questions with 19 symptoms scales. All of the multi-item scales and single-item measures range in score from 0 to 100. A high score represents a high level of symptomatology or problems. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Head and Neck Cancer-specific Quality of Life | Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-HN43). This is the head and neck cancer specific module that contains 43 questions with 19 symptoms scales. All of the multi-item scales and single-item measures range in score from 0 to 100. A high score represents a high level of symptomatology or problems. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Body Weight | Assessed by bioelectrical impedance. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Body Weight | Assessed by bioelectrical impedance. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Body Mass Index | Assessed by participant's weight in kilograms divided by the square of height in meters. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Body Mass Index | Assessed by participant's weight in kilograms divided by the square of height in meters. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Muscle Mass | Assessed by bioelectrical impedance. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Muscle Mass | Assessed by bioelectrical impedance. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Percentage of Body Fat | Assessed by bioelectrical impedance. | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Percentage of Body Fat | Assessed by bioelectrical impedance. | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| C-Reactive Protein |  | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| C-Reactive Protein |  | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Albumin |  | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Albumin |  | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Hemogram |  | Change from Baseline (at diagnosis) to 1-3 days before the beginning of radiotherapy | 
| Hemogram |  | Change from 1-3 days before the beginning of radiotherapy to 4 Weeks after last radiotherapy session | 
| Unplanned hospital visits |  | From baseline to 4 Weeks after last radiotherapy session | 
| Compliance to Chemotherapy | Assessed as the average relative chemotherapy dose-intensity received for the originally planned regimen based on standard formulas. | Through chemotherapy completion, an average of 7 weeks | 
| Compliance to Radiotherapy | Assessed assessed as the completion of prescribed dose of radiation during the prescribed time frame. | Through radiotherapy completion, an average of 7 weeks | 
| Treatment-Related Adverse Events | Assessed by CTCAE-vs.5. | From the beginning of radiotherapy/chemotherapy to 4 Weeks after last radiotherapy session | 
| Progression-Free Survival | Defined as the time from randomization to the occurrence of disease progression or death. | From baseline to 5 years after diagnosis | 
| Overall Survival | Defined as the time from randomization to death from any cause. | From baseline to 5 years after diagnosis | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prehabilitation, Exercise, Head and Neck Cancer