PREoperativ Study of Exercise Training (PRESET-RCT)

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

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 Overview

• Status: Active, not recruiting
• Conditions: GastroEsophageal Cancer
• Intervention / Treatment: Behavioral: Exercise training

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EX group; Exercise training	Behavioral: Exercise training; 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.
No Intervention: CON-group; Usual Care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jesper Frank Christensen, PhD
• Collaborators: Lundbeck Foundation; Region Capital Denmark; Beckett Foundation
• Investigators: Study Chair: Lars B Svendsen, DMSc, Rigshospitalet, Denmark; Principal Investigator: Jesper F Christensen, PhD, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (Actual): April 6, 2018

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 19, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: exercise training; treatment tolerability; treatment complications
• Other Study ID Numbers: PRESET-RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No