Postoperative Exercise Training and Colorectal Cancer Liver Metastasis
- Conditions
- Cancer ColorectalCancer Metastatic to Liver
- Interventions
- Other: Exercise
- Registration Number
- NCT05579340
- Lead Sponsor
- Rigshospitalet, Denmark
- Brief Summary
Up to 25% of colorectal cancer (CRC) patients are diagnosed with liver metastases, which is the most common site of metastasis, already during the primary tumor diagnosis. Another 30% of the patients will develop liver metastases at a later stage. Even though patient can be treated by surgical resection of the metastatic tumor, 50-75% of the patients experience a relapse in less than two years. Due to the high probability of relapse, mCRC patients undergo multiple rounds of surgery and adjuvant treatment (chemotherapy/radiotherapy) which results in substantial physical de-conditioning.
Physical activity has been shown to increase the progression-free survival rates in mCRC patients, when applied post-diagnosis. Increased cardiorespiratory fitness (VO2peak) at the time of diagnosis among CRC individuals has been associated with lower risk of all-cause mortality. Although data on the effect of chronic exercise on VO2peak have emerged, thus far, there is no randomized clinical trial that has investigated the effects of exercise training in mCRC patients early after surgical treatment with curative intent.
Therefore, this project aims to address the beneficial effect of structured exercise training primarily on VO2peak and tumor recurrence in mCRC patients immediately after surgical treatment and while they are undergoing adjuvant chemotherapy/radiotherapy.
A total of 66 participants will be recruited from the Department of Surgery and Transplantation, Rigshospitalet and randomly allocated to a standard care control group (n=22), standard care plus 150 min/week exercise training (n=22) or standard care plus 300 min/week exercise training (n=22). Participants will undergo exercise training for 6 months, starting immediately after surgery, and they will be followed for additional 6 months. Tumor recurrence will be evaluated up to 3 years after training initiation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 66
- Colorectal cancer patients diagnosed with liver metastasis and scheduled for liver metastasis surgical resection
- Age <18
- Pregnancy
- Physical or mental disabilities that prohibit execution of test or training procedures
- Inability to understand the Danish language.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ex1 Exercise Low exercise volume (150 min/week) Ex2 Exercise High exercise volume (300 min/week)
- Primary Outcome Measures
Name Time Method Change in peak oxygen consumption (VO2peak) Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in VO2peak assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer
- Secondary Outcome Measures
Name Time Method Changes in Anxiety Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported anxiety, assessed using the Hospital Anxiety and Depression Scale (HADS) (scale scoring: 0-21, the higher the score the worse the condition)
Changes in Circulating tumor DNA (ctDNA) Baseline, 6-, and 12 months after exercise training initiation Changes in ctDNA in blood
Changes in Health-related quality of life: Emotional well-being Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported emotional well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-24, the higher the score the better quality of life)
Changes in Health-related quality of life: Functional well-being Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported functional well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)
Changes in Health-related quality of life: General Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported general health-related qualify of life assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-108, the higher the score the better quality of life)
Changes in Health-related quality of life: total score Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported in health-related quality of life (total score) assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-136, the higher the score the better quality of life)
Changes in Health-related quality of life: Trial outcome index Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported trial outcome index assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-84, the higher the score the better quality of life)
Changes in Health-related quality of life: Fatigue Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported fatigue assessed using the Functional Assessment of Cancer Therapy - Fatigue scale (FACIT-Fatigue) (scale score: 0-52, the higher the score the less fatigue)
Changes in Physical activity: Walking Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ)
Changes in Physical activity: Moderate intensity physical activity Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported weekly duration of moderate intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)
3-years overall survival Randomization to 3 years after randomization Proportion of patients who are alive 3 years after randomization
Changes in Muscle strength: Hand grip strength Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in hand grip strength, assessed using a dynamometer
Changes in Functional performance: Maximal gait speed Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in maximal gait speed
Changes in Body composition and anthropometrics: Body mass Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in body mass
Changes in Body composition and anthropometrics: Total lean mass Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in total lean mass assessed by dual energy x-ray absorptiometry (DXA)
Changes in Blood biochemistry: leukocyte differential counts Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting leukocyte differential counts (total and per type \[eosinophils, basophils, lymphocytes, monocytes, neutrophils\])
Changes in Blood biochemistry: Triglycerides Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting triglycerides blood levels
Changes in Blood biochemistry: HDL-Cholesterol Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting HDL-cholesterol blood levels
Changes in Cytokine levels in blood: Interferon gamma (IFN-gamma) Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting IFN-gamma blood levels
Changes in Immune cells in blood: CD8 T cells Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting CD8 T cells
Changes in Immune cells in blood: B cells Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting B cells
Changes in Patient-reported symptomatic adverse events Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
Changes in Health-related quality of life: Physical well-being Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported physical well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)
3-years recurrence-free survival Randomization to 3 years after randomization Proportion of patients who survive without relapse (formation of new tumors) for the 3-year period
Changes in Functional performance: Stair climbing performance Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in time required to climb a specific staircase
Changes in Body composition and anthropometrics: Total fat mass Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in total fat mass assessed by DXA
Changes in Diastolic Blood pressure Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting diastolic blood pressure
Changes in Health-related quality of life: Colorectal cancer specific Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported colorectal-cancer specific health-related quality of life assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)
Changes in DNA methylation Baseline, 6-, and 12 months after exercise training initiation Changes in DNA methylation derived from blood
Changes in Heart rate Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting heart rate
Changes in Blood biochemistry: C-reactive protein Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting C-reactive protein levels in blood
Changes in Blood biochemistry: Glucose Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting glucose blood levels
Changes in Blood biochemistry: LDL-Cholesterol Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting LDL-cholesterol blood levels
Changes in Cytokine levels in blood: Interleukin-6 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-6 blood levels
Changes in Cytokine levels in blood: Interleukin-1 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-1 blood levels
Changes in Cytokine levels in blood: Interleukin-7 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-7 blood levels
Changes in Cytokine levels in blood: Interleukin-8 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-8 blood levels
Changes in Cytokine levels in blood: Interleukin-15 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-15 blood levels
Changes in Cytokine levels in blood: Interleukin-10 Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-10 blood levels
Changes in Cytokine levels in blood: Tumor-necrosis-factor alpha (TNFalpha) Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting TNFalpha blood levels
Changes in Muscle strength: Leg press maximal muscle strength Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in leg press one repetition maximum (1RM)
Changes in Systolic Blood pressure Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting systolic blood pressure
Changes in Blood biochemistry: Insulin Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting insulin blood levels
Changes in Aerobic Capacity: Ventilatory threshold Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in ventilatory threshold assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer
Changes in Aerobic Capacity: Peak power output Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in peak power output assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer
Changes in Functional performance: Habitual gait speed Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in habitual gait speed
Changes in Functional performance: 30 seconds Sit-to-stand Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in the number of stands from sitting position that can be performed during 30 seconds
Changes in Body composition and anthropometrics: Bone mineral density Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in bone mineral density assessed by DXA
Changes in Body composition and anthropometrics: Waist circumference Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in waist circumference
Changes in Body composition and anthropometrics: Hip circumference Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in Hip circumference
Changes in Cytokine levels in blood: Interleukin-1β Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting Interleukin-1β blood levels
Changes in Osteonectin Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting osteonectin blood levels
Changes in Depression Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation 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)
Changes in Physical activity: Vigorous intensity physical activity Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported weekly duration of vigorous intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)
Changes in Physical activity: Total intensity physical activity Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported weekly duration of total intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ) (Expressed as metabolic equivalent (MET)-min per week: MET level x minutes of activity x events per week)
Changes in Immune cells in blood: Natural killer (NK) cells Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting NK cells
Changes in Immune cells in blood: CD4 T cells Baseline, 3-, 6-, 9- and 12 months after exercise training initiation Changes in resting CD4 T cells
Changes in Health-related quality of life: Social well-being Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported social well-being assessed using the Functional Assessment of Cancer Therapy - Colorectal (FACT-C) (scale scoring 0-28, the higher the score the better quality of life)
Changes in Physical activity: sitting time Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation Changes in patient-reported weekly sitting time, assessed using the International Physical Activity Questionnaire (IPAQ)
Changes in treatment tolerance: Relative dose intensity (RDI) of adjuvant chemotherapy From date of planned initiation to end of adjuvant chemotherapy RDI (%) of adjuvant chemotherapy, calculated as the actual dose intensity / standard dose intensity x 100%
Postoperative hospital admissions From discharge to 12 months after exercise training initiation Incidence of postoperative hospital re-admissions, defined as any non-scheduled ≥ 24 h hospitalization
Postoperative complications From discharge to 30 days after discharge Incidence of postoperative complications up to 30 days after surgery (total and by grade and type), assessed using the Clavien-Dindo classification
Trial Locations
- Locations (1)
Rigshospitalet (CFAS)
🇩🇰Copenhagen, Denmark