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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 310
- Locations
- 1
- Primary Endpoint
- Risk of treatment failure
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 85 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Risk of treatment failure
Time Frame: From date of randomization, until the date of treatment failure is clinically determined before scheduled surgery assessed for up to 20 weeks
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
Secondary Outcomes
- 3 year disease free survival(Baseline to 3 year follow-up)
- Risk of neoadjuvant treatment complications(From date of randomization to the date of surgery, up to 20 weeks)
- Risk of post-operative complications(From surgery to 30 days post surgery)
- Time to disease progression(Baseline to 3 year follow-up)
- Health Related Quality of Life(Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up)
- Lean Body Mass(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(Baseline to scheduled surgery)
- Interleukin (IL)-6(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(From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks)
- 3 year overall survival(Baseline to 3 year follow-up)
- Anxiety and Depression(Baseline, scheduled surgery, 1-year follow-up, 2-year follow-up, 3-year follow-up)
- Total length of hospital stays(From date of randomization up to 30 days after surgery)
- Cardiopulmonary fitness(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(From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks)
- Leg-extensor power(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(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(From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks)
- Risk of neoadjuvant treatment dose-reduction(From date of randomization to the date of surgery, up to 20 weeks)
- Maximum muscle strength(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(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(From visit 1 (date of randomization, before neoajuvant treatment) until to visit 2 (the week before surgery, after neoadjuvant treatment) up to 20 weeks)
- Pre-operative risk of hospitalization(From date of randomization, until the date of hospitilization before scheduled surgery assessed for up to 20 weeks)
- Tumor regression grade(From date of randomization (baseline tumor biopsy) to tumor resection (surgery), up to 20 weeks)
Investigators
Jesper Frank Christensen, PhD
Postdoc
Rigshospitalet, Denmark