PREoperativ Study of Exercise Training

Study Overview
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Brief Summary
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Background Patients undergoing resection for gastro-esophageal (GE)-cancer are subjected to high burden of disease and treatment-specific morbidities with potential detrimental impact on survival and quality of life. Exercise training is a promising strategy to improve physical functional before and after tumor resection, but it is not established if this translates into lower risk of peri- and post-operative complications, improved treatment tolerance. Objectives: To explore the effect a preoperative exercise-training intervention on the risk of treatment failure, defined as the risk of not reaching surgery, in patients diagnosed with operable GE cancer. To explore the effect of preoperative exercise training on median time to tumor progression (disease free survival), and overall survival To explore the effect of preoperative exercise training on the risk of treatment complications To explore the effect of preoperative exercise training on health related quality of life, anxiety and depression,cardiopulmonary fitness, muscle strength, and body composition Subjects and Methods In total, 310 GE-cancer patients will be included in the study and randomly allocated to pre-operative exercise training (n=155) or usual care control (n=155). All participants will undergo 2 study visits; assessed for cardiopulmonary fitness; muscle strength, body composition; blood sample (50 ml); quality of life by questionnaires; physical function; and blood volume profile. Quality of life will be assessed by questionnaires by self-report three times (at 12, 24, and 36 months after diagnosis), and we will collect data from medical records regarding mortality and disease recurrence up to 36 months after diagnosis. Treatment arms: The intervention-group will be prescribed 2-3 weekly supervised exercise training for a total of 12 weeks before surgery during neo-adjuvant chemotherapy. The control group will follow current usual care guidelines. After surgery during adjuvant chemotherapy, both groups will be referred to municipality-based rehabilitation.

Official Title
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PREoperativ Study of Exercise Training-RCT: A Phase 3 Randomized Controlled Trial of Preoperative Exercise Training vs Usual Care During Neoadjuvant Treatment in Patients With Gastroesophageal Cancer

Conditions
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GastroEsophageal Cancer

Intervention / Treatment
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* Behavioral: Exercise training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with histologically verified, resectable adenocarcinoma of the esophagus, stomach or gastro-esophageal junction Exclusion Criteria: Deemed inoperable at the point of diagnoses Pregnancy Any other known malignancy requiring active treatment Not eligible for preoperative chemo- or chemoradiotherapy Performance status > 1 Physical disabilities precluding physical testing and/or exercise Inability to read and understand Danish

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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 |
| --- | --- |
| Active Comparator: EX group<br>Exercise training | Behavioral: Exercise training<br>* Structured, supervised, high-intensity combined aerobic and resistance exercise. Based on patients' individual capacity (Wattmax and 1RM), a personalized exercise program will be prescribed. Following a 5 minutes warm up, the patients will perform 21 min of aerobic interval training on a stationary bicycle consisting of three 4 minute high intensity intervals (85-95% HRmax) with 3 minutes of active pause between each interval. The resistance training comprises 4 functional exercises by performed using bodyweight, elastic resistance bands or kettlebells followed by resistance exercises in machines for the major muscle groups: chest press, leg press, seated rows, and leg extension with 1 warm-up set followed by 3-4 sets of 8 to 12 repetitions.<br>|
| No Intervention: CON-group<br>Usual Care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk of treatment failure | The frequency of patients scheduled to receive neo-adjuvant treatment and tumor resection with curative intend, but fail to reach surgery due to death, disease progression or physical deterioration | From date of randomization, until the date of treatment failure is clinically determined before scheduled surgery assessed for up to 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to disease progression | Time from point of diagnosis to clinical disease relapse | Baseline to 3 year follow-up | 
| 3 year disease free survival | Frequency of patients alive without clinical disease relapse 3 years after diagnosis | Baseline to 3 year follow-up | 
| 3 year overall survival | Frequency of patients alive 3 years after diagnosis | Baseline to 3 year follow-up | 
| Health Related Quality of Life | Changes from baseline in the Functional Assessment of Cancer Therapy (FACT) questionaire | Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up | 
| Anxiety and Depression | Changes from baseline in the HADs questionaire | Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up | 
| Pre-operative risk of hospitalization | Frequency of non-scheduled hospitalization during neoadjuvant treatment | From date of randomization, until the date of hospitilization before scheduled surgery assessed for up to 20 weeks | 
| Total length of hospital stays | Total number of days hospitalized | From date of randomization up to 30 days after surgery | 
| Tumor regression grade | Pathology assessment of tumor response to neoadjuvant treatment | From date of randomization (baseline tumor biopsy) to tumor resection (surgery), up to 20 weeks | 
| Risk of neoadjuvant treatment dose-reduction | Incidence of dose-reduction | From date of randomization to the date of surgery, up to 20 weeks | 
| Risk of neoadjuvant treatment complications | Incidence of registered toxicities (graded 1-4) | From date of randomization to the date of surgery, up to 20 weeks | 
| Risk of post-operative complications | Incidence of registered post-operative complications (Clavien-Dindo grade 2-4) | From surgery to 30 days post surgery | 
| Cardiopulmonary fitness | Changes in VO2peak | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Maximum muscle strength | Changes in 1 repetition maximum strength leg-press | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Lean Body Mass | Changes in whole-body lean mass assessed by dual energy x-ray absorptiometry (DXA) scan | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Fat percentage | Changes in whole-body fat percentage assessed by DXA scan | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Appendicular lean mass | Changes in appendicular lean mass assessed by DXA scan | Baseline to scheduled surgery | 
| Leg-extensor power | Changes in maximum leg power assessed by Nottingham Power Rig | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Blood Volume | Changes in blood volume assessed by CO2 rebreathing | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| TNFa | Changes in plasma TNFa concentration | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| Interleukin (IL)-6 | Changes in plasma IL-6 concentration | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| CRP | Changes in plasma CRP concentration | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| HbA1c | Changes in plasma HbA1c concentration | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 
| IL-10 | Changes in plasma IL-10 concentration | From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise training, treatment tolerability, treatment complications