Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Study Overview
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Brief Summary
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Patients with advanced gastroesophageal cancer are in great risk of losing skeletal muscle mass and developing cancer cachexia. Low skeletal muscle mass has a negative impact on quality of life, impairs physical function, increases toxicity from anti-neoplastic treatment, as well as increases risk of death. Resistance training and protein supplements have the potential to stimulate muscle anabolism and counteract loss of skeletal muscle mass. Therefore, the investigators have designed a randomized controlled feasibility trial to evaluate the feasibility, safety and the therapeutic effect of resistance training and protein supplements in patients with advanced gastroesophageal cancer undergoing first line chemotherapy. A total of 54 patients with advanced gastroesophageal cancer will be recruited from the Department of Oncology, Copenhagen University Hospital, Rigshospitalet and randomly allocated 2:1 to standard care plus resistance training 3 times pr. week and a daily supplement of protein or to standard care alone.

Official Title
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Feasibility and Effect of Resistance Training and Protein Supplementation in Patients With Advanced Gastroesophageal Cancer

Conditions
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Gastro-esophageal Cancer

Intervention / Treatment
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* Behavioral: Resistance training
* Dietary Supplement: Protein supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically verified, non-resectable cancer of the esophagus, stomach, or gastroesophageal junction referred to first line chemotherapy. Exclusion Criteria: Age < 18 Living outside the greater Copenhagen area Any other malignancy requiring active treatment Not eligible for chemotherapy Performance status > 2 Not able to swallow liquids Parenteral nutrition or enteral nutrition via feeding tube Physical or mental disabilities that prohibit execution of test or training procedures Pregnancy Inability to understand the Danish language

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard Care Control<br>Participants allocated to control receive first line chemotherapy the standard patient care program, as provided by Rigshospitalet, Copenhagen, Denmark. Participants allocated to control are allowed to exercise on their own initiative or participate in any standard care hospital- or municipality-based exercise training program. There will be no diet restrictions. | |
| Experimental: Exercise and protein supplements intervention group<br>Participants allocated to intervention receive first line chemotherapy and the standard patient care program, as provided by Rigshospitalet, Copenhagen, Denmark. The intervention consists of resistance training and a daily protein supplement. | Behavioral: Resistance training<br>* 10 weeks of resistance training 3 times pr. week.<br>Dietary Supplement: Protein supplement<br>* A daily supplement of protein to ensure a daily intake of 1,6g protein/kg bodyweight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise feasibility: Exercise sessions attendance | The number of attended exercise training sessions relative to the number of planed exercise sessions | From baseline until end of intervention (10 weeks) | 
| Exercise feasibility: Relative dose-intensity of protein supplement | The actual amount consumed relative to the amount prescribed over the intervention period | From baseline until end of intervention (10 weeks) | 
| Incidence of Serious Adverse Events (SAEs). | SAE will be recorded during trial assessment visits and through medical records. This procedure will concern any SAE during the trial period. For each trial visit we will collect patients' self-report of SAEs, which may have occurred during the period since the last trial visit. | Baseline until end of intervention (10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise feasibility: Relative dose intensity of exercise | The actual dose relative to the prescribed minimum dose | Baseline until end of intervention (10 weeks) | 
| Exercise feasibility: Early termination of exercise sessions | Termination of an exercise session before the prescribed exercises have been performed | Baseline until end of intervention (10 weeks) | 
| Exercise feasibility: Exercise intervention interruptions | Incidence of exercise intervention disruptions, defined as a period of ≥ 7 days without an attended exercise session | Baseline until end of intervention (10 weeks) | 
| Exercise feasibility: Permanent discontinuation | Incidence of permanent withdrawal from the intervention before intervention period has ended. | Baseline until end of intervention (10 weeks) | 
| Body composition and anthropometrics: Total lean mass | Changes in total lean mass, assessed by dual energy x-ray absorptiometry (DXA) | Baseline, end of week 10 | 
| Body composition and anthropometrics: Appendicular lean mass | Changes in appendicular lean mass, assessed by DXA | Baseline, end of week 10 | 
| Body composition and anthropometrics: Total fat mass | Changes in total fat mass, assessed by DXA | Baseline, end of week 10 | 
| Body composition and anthropometrics: Fat percentage | Changes in fat percentage, assessed by DXA | Baseline, end of week 10 | 
| Body composition and anthropometrics: Bone mineral density | Changes in bone mineral density, assessed by DXA | Baseline, end of week 10 | 
| Body composition and anthropometrics: Muscle thickness | Changes in thickness of the vastus lateralis, assessed by ultrasound | Baseline, end of week 10 | 
| Body composition and anthropometrics: Skeletal muscle index | Changes in skeletal muscle index, assessed by diagnostic CT scans | At diagnose, after 10 weeks intervention and at 1 year follow up | 
| Body composition and anthropometrics: Skeletal muscle attenuation | Changes in skeletal muscle attenuation, assessed by diagnostic CT scans | At diagnose, end of week 10 | 
| Body composition and anthropometrics: Adipose tissue index | Changes in adipose tissue index, assessed by diagnostic CT scans | At diagnose, end of week 10 | 
| Body composition and anthropometrics: Body mass | Changes in body mass | Baseline, end of week 10 | 
| Body composition and anthropometrics: Body mass index | Changes in body mass index | Baseline, end of week 10 | 
| Body composition and anthropometrics: Hip circumference | Changes in hip circumference | Baseline, end of week 10 | 
| Body composition and anthropometrics: Waist circumference | Changes in waist circumference | Baseline, end of week 10 | 
| Muscle strength: Leg press maximal muscle strenght | Changes in leg press one repetition maximum (1RM) | Baseline, end of week 10 | 
| Muscle strength: Chest press maximal muscle strenght | Changes in chest press 1RM | Baseline, end of week 10 | 
| Muscle strength: Hand grip strenght | Changes in hand grip strength, assessed using a dynamometer | Baseline, end of week 10 | 
| Functional performance: Habituel gait speed | Changes in habitual gait speed | Baseline, end of week 10 | 
| Functional performance: Maximal gait speed | Changes in maximal gait speed | Baseline, end of week 10 | 
| Functional performance: Sit-to-stand | Changes in sit-to-stand power. | Baseline, end of week 10 | 
| Functional performance: Stair climb | Changes in stair climbing power | Baseline, end of week 10 | 
| Resting metabolic rate | Changes in resting metabolic rate | Baseline, end of week 10 | 
| Blood pressure: Systolic blood pressure | Changes in systolic blood pressure | Baseline, end of week 10 | 
| Blood pressure: Diastolic blood pressure | Changes in diastolic blood pressure | Baseline, end of week 10 | 
| Heart rate | Changes in resting heart rate | Baseline, end of week 10 | 
| 1 and 2-years cancer-specific survival | Proportion of patients who have not died from gastroesophageal cancer 1 and 2 years after randomization | Randomization to 1 and 2 years after randomization | 
| 1 and 2-years over-all survival | Proportion of patients who have not died 1 and 2 years after randomization | Randomization to 1 and 2 years after randomization | 
| Progression-free survival | Time to progression | Randomization to 2 years after randomization | 
| Treatment tolerance: Hospitalization | Unscheduled hospitalization | 3, 6 and 9 weeks after randomization | 
| Treatment tolerance: Relative dose intensity | Treatment tolerance assessed by the delivery of chemotherapy (relative dose intensity) | 3, 6 and 9 weeks after randomization | 
| Treatment tolerance: Number of series recieved | Treatment tolerance assessed by the delivery of chemotherapy (number of series recieved) | 3, 6 and 9 weeks after randomization | 
| Treatment tolerance: Tolerated dose | Treatment tolerance assessed by the delivery of chemotherapy (dose reduction) | 3, 6 and 9 weeks after randomization | 
| Treatment tolerance: Permanent discontinuation of the treatment | Treatment tolerance assessed by the delivery of chemotherapy (permanent discontinuation of the treatment) | 3, 6 and 9 weeks after randomization | 
| Treatment effect: Response to chemotherapy | Response to chemotherapy assessed by Response Evaluation Criteria in Solid Tumors 1.1 (complete response, partiel response, stable disease, progressive disease) | Randomization to 2 years after randomization | 
| Health-related quality of life: Physical well-being | Changes in patient-reported physical well-being assessed using the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) (scale-scoring 0-28, the higher the score the better quality of life) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Health-related quality of life: Social well-being | Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Health-related quality of life: Emotional well-being | Changes in patient-reported social well-being assessed using FACT-E (scale-scoring 0-24, the higher the score the better quality of life) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Health-related quality of life: Functional well-being | Changes in patient-reported functional well-being assessed using FACT-E (scale-scoring 0-28, the higher the score the better quality of life) | Baseline,10 weeks-, 1 year-, 2 years after randomization | 
| Health-related quality of life: gastroesophageal cancer specific | Changes in patient-reported gastroesophageal cancer specific well-being assessed using FACT-E (scale-scoring 0-68, the higher the score the better quality of life) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Health-related quality of life: cancer cachexia specific | Changes in patient-reported cancer cachexia specific well-being assessed using Functional Assessment of Cancer Therapy - Cancer Cachexia (scale-scoring 0-48, the higher the score the better quality of life) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Depression | Changes in patient-reported depression, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Anxiety | Changes in patient-reported anxiety, assessed using the HADS (scale scoring: 0-21, the higher the score the worse the condition) | Baseline, 10 weeks-, 1 year-, and 2 years after randomization | 
| Self-reported physical activity: Walking | Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ) | Baseline, end of week 10 | 
| Self-reported physical activity: Moderate intensity physical activity (PA) | Changes in patient-reported weekly duration of moderate intensity PA, assessed using the IPAQ | Baseline, end of week 10 | 
| Self-reported physical activity: Vigorous intensity PA | Changes in patient-reported weekly duration of vigorous intensity PA, assessed using the IPAQ | Baseline, end of week 10 | 
| Self-reported physical activity: Total PA | Changes in patient-reported weekly duration of total PA, assessed using the IPAQ (Expressed as metabolic equivalent (MET)-min per week: MET level x minutes of activity x events per week) | Baseline, end of week 10 | 
| Self-reported physical activity: Sitting time | Changes in patient-reported weekly duration of sitting time, assessed using the IPAQ | Baseline, end of week 10 | 
| Self-reported screening of sarcopenia | Changes in patient-reported signs of sarcopenia, assessed using The Strength, assistance in walking, rise from a chair, climb stairs, and falls (SARC-F) questionnaire (scale scoring: 0-10, the higher the score the better the condition) | Baseline, end of week 10 | 
| Self-reported three-days dietary records | Changes in patient-reported three-day record of dietary intake assessed using questionnaries. | Baseline, week 5 and week 10 | 
| Patient-reported symptomatic adverse events | Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) | One week after each serie of chemotherapy during the intervention (10 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise oncology, Resistance exercise, Cancer, Cancer cachexia, Protein supplements, Sarcopenia, Palliative chemotherapy