Postoperative Exercise Training and Colorectal Cancer Liver Metastasis

Cancer Colorectal Clinical Trial

— mCRC-POET  

Official title:

Post-Operative Exercise Training in Patients With Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05579340
• Other study ID #: mCRC-POET
• Status: Recruiting
• Phase: N/A
• Start date: April 2023
• Est. completion date: April 2025

Study information

• Verified date: April 2023
• Source: Rigshospitalet, Denmark
• Contact: Christina Yfanti, PhD
• Phone: +4535457641
• Email: christina.yfanti[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: April 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Colorectal cancer patients diagnosed with liver metastasis and scheduled for liver metastasis surgical resection

Exclusion Criteria:

• Age <18

• Pregnancy

• Physical or mental disabilities that prohibit execution of test or training procedures

• Inability to understand the Danish language.

Related Conditions & MeSH terms

• Cancer Colorectal
• Colorectal Neoplasms

Intervention

Other:
• Exercise
6 months of combined aerobic and resistance exercise

Locations

Country	Name	City	State
Denmark	Rigshospitalet (CFAS)	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in peak oxygen consumption (VO2peak)	Changes in VO2peak assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	3-years recurrence-free survival	Proportion of patients who survive without relapse (formation of new tumors) for the 3-year period	Randomization to 3 years after randomization
Secondary	3-years overall survival	Proportion of patients who are alive 3 years after randomization	Randomization to 3 years after randomization
Secondary	Changes in Aerobic Capacity: Ventilatory threshold	Changes in ventilatory threshold assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Aerobic Capacity: Peak power output	Changes in peak power output assessed during an incremental exercise test to volitional exhaustion on a bicycle ergometer	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Muscle strength: Hand grip strength	Changes in hand grip strength, assessed using a dynamometer	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Muscle strength: Leg press maximal muscle strength	Changes in leg press one repetition maximum (1RM)	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Functional performance: Habitual gait speed	Changes in habitual gait speed	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Functional performance: Maximal gait speed	Changes in maximal gait speed	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Functional performance: Stair climbing performance	Changes in time required to climb a specific staircase	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Functional performance: 30 seconds Sit-to-stand	Changes in the number of stands from sitting position that can be performed during 30 seconds	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Body mass	Changes in body mass	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Total lean mass	Changes in total lean mass assessed by dual energy x-ray absorptiometry (DXA)	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Total fat mass	Changes in total fat mass assessed by DXA	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Bone mineral density	Changes in bone mineral density assessed by DXA	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Waist circumference	Changes in waist circumference	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Body composition and anthropometrics: Hip circumference	Changes in Hip circumference	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Systolic Blood pressure	Changes in resting systolic blood pressure	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Diastolic Blood pressure	Changes in resting diastolic blood pressure	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Heart rate	Changes in resting heart rate	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: leukocyte differential counts	Changes in resting leukocyte differential counts (total and per type [eosinophils, basophils, lymphocytes, monocytes, neutrophils])	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: C-reactive protein	Changes in resting C-reactive protein levels in blood	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: Insulin	Changes in resting insulin blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: Glucose	Changes in resting glucose blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: Triglycerides	Changes in resting triglycerides blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: LDL-Cholesterol	Changes in resting LDL-cholesterol blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Blood biochemistry: HDL-Cholesterol	Changes in resting HDL-cholesterol blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-6	Changes in resting Interleukin-6 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-1	Changes in resting Interleukin-1 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-7	Changes in resting Interleukin-7 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-8	Changes in resting Interleukin-8 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-15	Changes in resting Interleukin-15 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-1ß	Changes in resting Interleukin-1ß blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interleukin-10	Changes in resting Interleukin-10 blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Tumor-necrosis-factor alpha (TNFalpha)	Changes in resting TNFalpha blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Cytokine levels in blood: Interferon gamma (IFN-gamma)	Changes in resting IFN-gamma blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Immune cells in blood: Natural killer (NK) cells	Changes in resting NK cells	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Immune cells in blood: CD4 T cells	Changes in resting CD4 T cells	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Immune cells in blood: CD8 T cells	Changes in resting CD8 T cells	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Immune cells in blood: B cells	Changes in resting B cells	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Osteonectin	Changes in resting osteonectin blood levels	Baseline, 3-, 6-, 9- and 12 months after exercise training initiation
Secondary	Changes in Patient-reported symptomatic adverse events	Patient-reported symptomatic adverse events, assessed using the using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Physical well-being	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Social well-being	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Emotional well-being	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Functional well-being	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: General	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Colorectal cancer specific	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: total score	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Trial outcome index	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Health-related quality of life: Fatigue	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Depression	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Anxiety	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Physical activity: Walking	Changes in patient-reported weekly duration of walking, assessed using the International Physical Activity Questionnaire (IPAQ)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Physical activity: Moderate intensity physical activity	Changes in patient-reported weekly duration of moderate intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Physical activity: Vigorous intensity physical activity	Changes in patient-reported weekly duration of vigorous intensity physical activity, assessed using the International Physical Activity Questionnaire (IPAQ)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Physical activity: Total intensity physical activity	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)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Physical activity: sitting time	Changes in patient-reported weekly sitting time, assessed using the International Physical Activity Questionnaire (IPAQ)	Baseline, 3-, 6-, 9-, 12-, 24- and 36 months after exercise training initiation
Secondary	Changes in Circulating tumor DNA (ctDNA)	Changes in ctDNA in blood	Baseline, 6-, and 12 months after exercise training initiation
Secondary	Changes in DNA methylation	Changes in DNA methylation derived from blood	Baseline, 6-, and 12 months after exercise training initiation
Secondary	Changes in treatment tolerance: Relative dose intensity (RDI) of adjuvant chemotherapy	RDI (%) of adjuvant chemotherapy, calculated as the actual dose intensity / standard dose intensity x 100%	From date of planned initiation to end of adjuvant chemotherapy
Secondary	Postoperative hospital admissions	Incidence of postoperative hospital re-admissions, defined as any non-scheduled = 24 h hospitalization	From discharge to 12 months after exercise training initiation
Secondary	Postoperative complications	Incidence of postoperative complications up to 30 days after surgery (total and by grade and type), assessed using the Clavien-Dindo classification	From discharge to 30 days after discharge