Progressive Resistance Training in Head and Neck Cancer Patients During Concomitant Chemoradiotherapy

Study Overview
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Brief Summary
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72 patients with head and neck cancer, undergoing primary treatment with radiation therapy and concomitant weekly cisplatin, will be recruited to this multicentre trial. Randomized 1:1 to either 12-week progressive resistance training (PRT) program or control arm, starting together with concomitant chemoradiotherapy (CCRT) Stratified by centre, gender, p16-status and body mass index (BMI) below or above 30. Primary endpoint is difference in change in lean body mass (LBM) between the groups and the endpoint is reduction of LBM loss in intervention arm by 25% compared to control. Secondary endpoints include side-effects to treatment, change in body composition, physical function and strength, and compliance to PRT. Questionnaires on QoL, diet, voluntary exercise and work affiliation will also be registered. Blood samples for explorative analyses will be drawn and optional muscle biopsies drawn for proteomics analyses and histological analyses.

Detailed Description
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The PRT program will start about the onset of radiotherapy. The program consists of 7 exercises in training machines and involves the major muscle groups of the body. The program has previously been found to successfully restore the loss of lean body mass (LBM) in head and neck cancer patients post-treatment. A group based approach will be used to facilitate a social and motivating training environment for the patients. A pilot study (NCT02068950) showed feasibility of PRT during CCRT. In addition to baseline data (height, tumor stage, performance status, etc), the following parameters will be registered: Weight, patient reported side effects, as well as a questionnaire on amount of physical activity and food intake. Physical function and strength will be tested at baseline, after the course of chemoradiotherapy and at the end of the 12-week PRT programme, and at 6 and 12 months follow-up. DXA scans for body composition will be performed using a Lunar iDXA (GE Healthcare). Blood samples will be drawn at regular intervals during the 12 weeks and at follow-up. Patient reported quality of life (EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-H&N35) will also be registered. Muscle biopsies will be taken three times: at baseline, after treatment and after 12-weeks PRT. Study duration is expected to be 18 months and an additional 12 months for follow-up.

Official Title
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Progressive Resistance Training in Head and Neck Cancer Patients During Concomitant Chemoradiotherapy - The DAHANCA 31 Study

Conditions
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Head and Neck Neoplasms, Weight Loss

Intervention / Treatment
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* Behavioral: Progressive Resistance Training
* Behavioral: physical activity
* Behavioral: Diet diary


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with biopsy verified head and neck squamous cell carcinoma referred for primary curatively intended treatment. Candidates for concomitant chemoradiotherapy (2Gyx33-34; 6F/W; weekly cisplatin 40mg/m2, max. 70 mg/weekly) according to Danish Head and Neck Cancer Group (DAHANCA) guidelines (T1-4, N1-3, M0) Performance status 0-1 At least 18 years of age. Exclusion Criteria: BMI below 20.5 diabetes corticosteroid treatment for other diseases Tonsillectomy within the last week before inclusion. hemoglobin below 6 mmol/l leucocytes below 2.5 x 10^9 /l thrombocytes below 50 x 10^9 /l comorbidities, social, familial or geographical conditions, that could compromise attendance or results

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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Progressive Resistance Training<br>12 weeks progressive resistance training (PRT) during and after concomitant chemoradiotherapy. Also optional/voluntary physical activity performed on their own is registered, as well as diet diary. | Behavioral: Progressive Resistance Training<br>* 12 weeks supervised resistance training program. Details of the program: 12 weeks, 3 sessions per week, 7 exercises in training machines (leg press, leg curl, hamstring curl, chest press, lateral pull down, sit-ups and back extensions). In general 2-3 sets of 8-15 repetitions will be performed following a progression plan starting with more repetitions at lower intensity progressing to fewer repetitions at higher intensity during the 12-week period (American College of Sports Medicine Position Stand)<br>Behavioral: physical activity<br>* Weekly diary of performed physical activity using the Physical Activity Score (PAS) during the 12-weeks intervention<br>* Other names: Diary of performed physical activity;Behavioral: Diet diary<br>* Weekly diet diary during the 12-weeks intervention<br>|
| Active Comparator: Control<br>Control arm. Optional/voluntary physical activity performed on their own is registered, as well as diet diary. | Behavioral: physical activity<br>* Weekly diary of performed physical activity using the Physical Activity Score (PAS) during the 12-weeks intervention<br>* Other names: Diary of performed physical activity;Behavioral: Diet diary<br>* Weekly diet diary during the 12-weeks intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LBM (lean body mass) | change in kilograms | at 12-weeks post PRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in LBM (lean body mass) | change in kilograms | at 6 weeks, and 6 and 12 months post RT | 
| Fat mass | change in kilograms | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Weight loss | in kilograms | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Patient reported pain | Measured by NRS-scale | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Patient reported Quality of Life | QLQ-C30 questionnaire | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Muscle strength | measured using chest press and leg press | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Chair rise | measured using 30 s. chair rise | at 6 and 12 weeks, and 6 and 12 months post RT | 
| arm curls | measured using 30 s. arm curls | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Stair climb | steps/sec | at 6 and 12 weeks, 6 and 12 months | 
| Compliance to PRT program | No. of attended sessions out of total | at 12 weeks post PRT | 
| Physical activity | measured by PAS (physical activity scale) | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Percent of patients with feeding tubes |  | at 6 and 12 weeks, and 6 and 12 months post RT | 
| Resumption of work | No. of days from end of radiotherapy until back at work at full time (or the hours of work per week as before therapy) | At 12 months follow-up | 
| Percent relapses | Percent of patients having relapse within 12 months after radiotherapy | at 12 months follow-up | 
| Cytokines | Measurement of different cytokines, changes over time and after bout of PRT. Will be measured regularly during the 12 weeks of PRT. | at 3, 6, 8, 10, and 12 weeks | 
| Muscle biopsies | protein will be measured using the proteomic approach. Muscle fiber type and size will be evaluated. | at 6 and 12 weeks, and at 12 months follow-up | 
| Patient satisfaction | Study specific questionnaire regarding pros and cons of attending the study | at 12 weeks | 
| NK-cells | Measuring NK-cells. NK-cells may increase after exercise and show tumor inhibiting effect. | at 3 and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Concomitant chemoradiotherapy, Exercise Training, Progressive Resistance Training, Weight loss, Lean Body Mass, Body Composition