Clinical trial NCT03490565: PREoperativ Study of Exercise Training
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: GastroEsophageal Cancer
Keywords: exercise training
treatment tolerability
treatment complications
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Lundbeck Foundation
name: Beckett Foundation
name: Region Capital Denmark
First posted: 2018-04-06
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Risk of treatment failure
timeFrame: From date of randomization, until the date of treatment failure is clinically determined before scheduled surgery assessed for up to 20 weeks
Secondary outcomes:
measure: Time to disease progression
timeFrame: Baseline to 3 year follow-up
measure: 3 year disease free survival
timeFrame: Baseline to 3 year follow-up
measure: 3 year overall survival
timeFrame: Baseline to 3 year follow-up
measure: Health Related Quality of Life
timeFrame: Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up
measure: Anxiety and Depression
timeFrame: Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up
measure: Pre-operative risk of hospitalization
timeFrame: From date of randomization, until the date of hospitilization before scheduled surgery assessed for up to 20 weeks
measure: Total length of hospital stays
timeFrame: From date of randomization up to 30 days after surgery
measure: Tumor regression grade
timeFrame: From date of randomization (baseline tumor biopsy) to tumor resection (surgery), up to 20 weeks
measure: Risk of neoadjuvant treatment dose-reduction
timeFrame: From date of randomization to the date of surgery, up to 20 weeks
measure: Risk of neoadjuvant treatment complications
timeFrame: From date of randomization to the date of surgery, up to 20 weeks
measure: Risk of post-operative complications
timeFrame: From surgery to 30 days post surgery
measure: Cardiopulmonary fitness
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Maximum muscle strength
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Lean Body Mass
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Fat percentage
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Appendicular lean mass
timeFrame: Baseline to scheduled surgery
measure: Leg-extensor power
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Blood Volume
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: TNFa
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: Interleukin (IL)-6
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: CRP
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: HbA1c
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
measure: IL-10
timeFrame: From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Jesper F Christensen, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Lars B Svendsen, DMSc
role: STUDY_CHAIR
References: