The SEHNeCa Supervised Exercise Project

Study Overview
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Brief Summary
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Objectives: To evaluate the effectiveness and efficiency of an innovative supervised exercise program for patients with head and neck cancer (SEHNeCa) to ameliorate loss of lean body mass, functional capacity and quality of life during one year, compared to a reference group receiving a physical activity prescription to be performed autonomously. To identify the optimal timing for applying the supervised exercise program: in a Prehabilitation period, at least 2 weeks before starting the conventional chemoradiotherapy treatment and concomitant with it, or during a Rehabilitation period, starting 12 weeks after the first radiotherapy session, once standard treatment has finished. Design: a multicenter, randomized clinical trial, where patients will be randomized to 3 groups: one control group and 2 experimental with different timing of exercise intervention. Population: 120 patients diagnosed with histological locally advanced stage III-IVa-b with squamous cell carcinomas of the larynx, pharynx, oral cavity, salivary or in neck lymph nodes from an unknown primary tumour treated with curative intent undergoing radiotherapy with or without concomitant chemotherapy. SEHNeCa program: is a 12-week exercise program supervised by specially trained instructors combining moderate to high intensity aerobic and strength exercises (three 1 hour sessions a week). Outcome measurements: main outcome variable: change in body mass index at 6 months (multy-frecuenciy imoediance). Secondary variables at basal, 7, 12, 25, and 52 weeks after the beginning of radiotherapy include quality of life (general SF-36 and cancer specific quality of life -European Organization for Research and Treatment of Cancer QLQ-C-30-),functional capacity (6 min walking test), patient reported outcomes and treatment maximum adverse events. Analyses: Differences between treatment groups in changes in outcome variables will be analyzed on an intention to treat basis. We will use linear mixed models for longitudinal analysis of repeated measurements of continuous outcomes (SAS PROC MIXED) and generalized logistic mixed models for dichotomous (SAAS PROC GLIMMIX), considering intercept and time courses as random effects and testing the significance of the interaction of time slopes by treatment group.

Official Title
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Supervised Exercise for Head and Neck Cancer Patients Initiated Previously or After Treatment: the SEHNeCa Randomized Controlled Trial

Conditions
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Neack and Head Cancer, Supervised Execise Program

Intervention / Treatment
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* Other: A supervised exercise program
* Other: exercise prescription


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosed locally advanced stage III-IVa-b with squamous cell carcinomas of the larynx, pharynx, oral cavity, salivary or in neck lymph nodes from an unknown primary tumour (TNM 9th AJCC classification; 2019.) treated with curative intent undergoing radiotherapy with or without concomitant chemotherapy (with or without previous surgery). Age: more than 18 years WHO performance status of 0-1 (IK 80%) Body mass index: more than 18.5. No evidence of metastatic disease No excessive alcohol intake (men > 21 and women > 14 units/week) No current or previous malignancies that could prevent participation and training No recent systematic resistance training. Exclusion Criteria: Decompensated heart disease, uncontrolled hypertension (TAS>200 o TAD>110), cardiac insufficiency (NYHA II o mayor), heart failure or constrictive pericarditis, Neutropenia, severe anemia ( Hb<8.0 g/dl), platelets count <50.000 microL Other health problems in which exercise is contraindicated. Carry out physical activity regularly (150 min/week of moderate activity or 75 of vigorous activity), measured with the PVS questionarie. Pregnancy Tracheostomy.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control<br>a physical activity prescription to be performed autonomously | Other: exercise prescription<br>* they will receive a prescription concerning healthy lifestyles and a personalized exercise plan<br>|
| Experimental: Prehabilitation<br>They will receive a supervised exercise programat least 2 weeks before starting the conventional chemoradiotherapy treatment and concomitant | Other: A supervised exercise program<br>* is a 12-week exercise program supervised by specially trained instructors combining moderate to high intensity aerobic and strength exercises (three 1 hour sessions a week).<br>|
| Experimental: Rehabilitation<br>They will receive a supervised exercise programat 12 weeks after the first radiotherapy session, once standard treatment has finished | Other: A supervised exercise program<br>* is a 12-week exercise program supervised by specially trained instructors combining moderate to high intensity aerobic and strength exercises (three 1 hour sessions a week).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body lean mass | change in body lean mass will be measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy) by the multi-frequency impedance measurement technique. | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of life | evaluated with the EORTCQLQ-C-30 questionnaire associated with the head and neck 35 specific module. Cancer specific quality of life is evaluated by the European Organisation for Research and Treatment of Cancer (QLQ-C-30) questionnaire (Aaronson et al., 1993). The QLQ-C-30 questionnaire includes five functional domains (physical, role, cognitive, emotional and social; higher scores represent greater function/quality of life) and three symptom scales (fatigue, pain and nausea; lower scores represent greater quality of life/less symptom severity) | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 
| Change in Functional capacity | Evaluated by the six minute walking test | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 
| Change in Strenght | Evaluated by a manual dynamometer for higher body and by the bench press for the lower body | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 
| Change in Quality of life | Evaluated by the Medical Outcomes Study 36- Item Short-Form Health Survey (SF-36). The HRQL questionnaire is measured blindly with self-administered questionnaires: the Spanish version of the SF-36 and. Questionnaire will be filled out before and after the intervention. SF-36 generates an 8-dimension health profile and two summary scores for the physical and mental components. This questionnaire has been validated in the Spanish population. | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 
| Change in Functional capacity | Evaluated by the shoulder pain disability index. patients place a mark on a 10cm visual analogue scale for each question. Verbal anchors for the pain dimension are 'no pain at all' and 'worst pain imaginable', and those for the functional activities are 'no difficulty' and 'so difficult it required help'. The scores from both dimensions are averaged to derive a total score. As more score, more pain the patients feels. | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy | 
| Change in Functional capacity | Evaluated by Fatigue-related measure with the FACIT-F test Predictor. a 13 items scale that measures the cancer related fatigue. The FACT-G scoring guide identifies those items that must be reversed before being added to obtain subscale totals. Negatively stated items are reversed by subtracting the response from 4. After reversing proper items, all subscale items are summed to a total, which is the subscale score.The higher score the score, the better the QOL. | Measured at baseline 7, 12, 25, and 52 weeks after the beginning of radiotherapy |