Randomized Controlled Trial of the Effects of Combined Resistance and AerobiC Exercise on Health-related Quality of Life in Patients Undergoing First-line Chemotherapy for Metastatic Colorectal Cancer (REACH) (REACH)

Effects of Exercise Training on Health-related Quality of Life in Patients With Unresectable Metastatic Colorectal Cancer: A Multi-center Randomized Controlled Trial

The primary objective of this trial is to compare the effects of 18 weeks structured exercise training versus on control on healt-related quality of life in patients with mCRC undergoing first-line chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer (mCRC)
• Intervention / Treatment: Other: Exercise training

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Casper Simonsen, PhD; Phone Number: +45 35 45 76 41; Email: casper.simonsen@regionh.dk

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Centre for Physical Activity Research, Copenhagen Univerisity Hospital - Rigshospitalet
    • Contact: Casper Simonsen, PhD; Phone Number: +45 35 45 76 41; Email: casper.simonsen@regionh.dk
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev and Gentofte Hospital
    • Contact: Louise Lang Lehrskov; Phone Number: 0045 38689394; Email: louise.lang.lehrskov.01@regionh.dk
  • Hillerød, Denmark, 3400
    • Recruiting
    • North Zealand University Hospital, Hillerød
    • Contact: Louise Lang Lehrskov; Email: louise.lang.lehrskov.01@regionh.dk
  • Roskilde, Denmark, 4000
    • Recruiting
    • Zealand University Hospital, Roskilde
    • Contact: Louise Lang Lehrskov; Phone Number: 35457641; Email: louise.lang.lehrskov.01@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

- Adults (≥18 years of age) schduled to undergo first-line chemotherapy for the treatment of metastatic colorectal cancer.

Exclusion criteria :

• Pregnancy.
• A life expectancy of < 6 months.
• Absolute contraindications to maximal exercise, as per the recommendations by the Danish Society of Cardiology.
• ECOG (Eastern Cooperative Oncology Group) performance status > 2.
• Inability to understand the Danish or English language.
• Engagement in structured moderate-to-high aerobic exercise training for >30 min >1 times/week for the past 3 months at the time of inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Participants allocated to the control group will receive standard care. No restrictions regarding physical activity will be imposed.
Experimental: Exercise training; Participants allocated to the exercise intervention group will receive standard care plus an exercise intervention. The exercise intervention will of consist moderate-to-high intensity supervised and unsupervised home-based exercise training (bicyling, walking, or running) 5 times/week for 18 weeks. After the initial 18-week intervention period, participants will be given the option to continue the intervention until week 162.	Other: Exercise training; Participants allocated to the exercise intervention group will receive standard care plus an exercise intervention. The exercise intervention will consist moderate-to-high intensity supervised and unsupervised home-based exercise training (bicyling, walking, or running) 5 times/week for 18 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	The difference in means of the average global health-related quality of life score in intervention versus control, regardless of intervention compliance; disease progression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative cancer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Scores range from 0 to 100, with higher scores indicating better health-related quality of life.	Every 3 weeks from randomization until post-intervention (18 weeks), withdrawal of consent to participate, or death (whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	The difference in means of the average health-related quality of life score (global score and score for each subcomponent) in intervention versus control, regardless of intervention compliance; disease progression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative cancer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Scores range from 0 to 100.	Randomization and 3, 6, 9, 12, 15, and 18 weeks after randomization or until withdrawal of consent to participate, or death (whichever occurs first). Followed-up at 36, 52, 104, and 156 weeks after randomization.
Colorectal cancer-specific symptoms	The difference in means of the average colorectal cancer-specific symptoms inter-vention versus control, regardless of intervention compliance; disease pro-gression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative can-cer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire CR 29. Scores range from 0 to 100.	Randomization and 3, 6, 9, 12, 15, and 18 weeks after randomization or until withdrawal of consent to participate, or death (whichever occurs first). Followed-up at 36, 52, 104, and 156 weeks after randomization.
Cancer related fatigue	Between-group difference in changes in cancer related fatigue from randomization to 6, 12, 18, 36, 52, 104, and 156 weeks after randomization. Cancer related fatigue will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core FA12. Scores range from 0 to 100.	Randomization and 3, 6, 9, 12, 15, and 18 weeks after randomization or until withdrawal of consent to participate, or death (whichever occurs first). Followed-up at 36, 52, 104, and 156 weeks after randomization.
Patient-reported symptomatic adverse events	Patient-reported symptomatic adverse events will be assessed, using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). A total of 42 symptomatic adverse events have been preselected based on high expected prevalence in patients with colorectal cancer.	7 days after every second cycle of treatment, starting from the second cycle. Each cycle is 2-3 weeks, depending on the regimen.
Serious adverse events	Serious adverse events.	From randomization to 20 weeks after randomization
Unscheduled hospitalizations	Unscheduled hospitalizations.	From randomization to 20 weeks after randomization
Dose delays of chemotherapy	A chemotherapy dose delay is a delay of the planned administation of chemotherapy.	From randomization to 20 weeks after randomization
Dose reductions of chemotherapy	A chemotherapy dose reduction is a decrease of the planned dose of chemotherapy.	From randomization to 20 weeks after randomization
Discontinuation of chemotherapy	Discontinuation of chemotherapy is a premature discontinuation of the planned chemotherapy.	From randomization to 20 weeks after randomization
Estimated maximal oxygen uptake	Between-group difference in changes from randomization to 18 weeks after randomization. Maximal oxygen uptake (mL/kg/min) will be estimated from ratings of perceived exertion obtained during submaximal exercise.	Randomization, 18 weeks after randomization
Estimated maximal oxygen uptake	Between-group difference in changes from randomization to 18 weeks after randomization. Maximal oxygen uptake (L/min) will be estimated from ratings of perceived exertion obtained during submaximal exercise.	Randomization, 18 weeks after randomization
Hand-grip strength	Between-group difference in changes from randomization to 18 weeks after randomization. Handgrip strength (kg) of the dominant hand will be measured using a dynamometer	Randomization, 18 weeks after randomization
Balance	Between-group difference in changes from randomizationto 18 weeks after randomization. Standing balance will be assessed using side-by-side stands, semi-tandem stands, and tandem stands. The time until the participants move their feet or grasp for support will be measured. The test is terminated after 10 seconds. Balance will be scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).	Randomization, 18 weeks after randomization
Habitual 4 m Gait Speed	Between-group difference in changes from randomization to 18 weeks after randomization. Habitual 4 m gait speed will be measured on a 4 m straight, flat walking course and scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).	Randomization, 18 weeks after randomization
Chair Rising Capacity	Between-group difference in changes from randomizationto 18 weeks after randomization. Chair rising capacity will be assessed using a sit-to-stand test. The time taken to perform five stands will be measured and scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).	Randomization, 18 weeks after randomization
Short Physical Performance Battery (SPPB) total score	Between-group difference in changes from randomization to 18 weeks after randomization. The Short Physical Performance Battery (SPPB) total score will be calculatedin accordance with the standardized scoring guidelines of the SPPB.	Randomization, 18 weeks after randomization
Lean mass	Between-group difference in changes from randomization to 18 weeks after randomization. Whole-body lean mass (kg) will be measured using bioelectrical impedance analysis.	Randomization, 18 weeks after randomization
Fat mass	Between-group difference in changes from randomization to 18 weeks after randomization. Whole-body fat mass (kg) will be measured using bioelectrical impedance analysis.	Randomization, 18 weeks after randomization
Body mass	Between-group difference in changes from randomizationto 18 weeks after randomization. Body mass (kg) will be measured using an electronic scale.	Randomization, 18 weeks after randomization
Body mass index	Between-group difference in changes from randomizationto 18 weeks after randomization.	Randomization, 18 weeks after randomization
Resting heart rate	Between-group difference in changes from randomization to 18 weeks after randomization. Reported as beats/min.	Randomization, 18 weeks after randomization
Systolic blood pressure	Between-group difference in changes from randomizationto 18 weeks after randomization. Reported as mmHg.	Randomization, 18 weeks after randomization
Diatolic blood pressure	Between-group difference in changes from randomizationto 18 weeks after randomization. Reported as mmHg.	Randomization, 18 weeks after randomization
Proportion of participants undergoing intended curative surgery from randomization to post-intervention.	Proportion of participants undergoing intended curative surgery.	From randomization to 20 weeks after randomization
5-year overall survival	Overall survival, defined as the time from randomization to death.	From randomization to 5 years after randomization
5-year progression-free survival, defined as the time from randomization to disease progression or death	5-year progression-free survival, defined as the time from randomization to disease progression or death.	From randomization to 5 years after randomization
Time to progression, defined as the time from randomization to disease progression	Time to progression, defined as the time from randomization to disease progression	From randomization to 5 years after randomization
Time to treatment failure	Time to treatment failure, defined as the time from initiation of treatment to early discontinuation.	From randomization to 5 years after randomization

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Colorectal cancer; Physical activity; Chemotherapy; Oncology; Metastatic colorectal cancer; Endurance training
• Additional Relevant MeSH Terms: Neoplasms by Site; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Behavior; Neoplasms; Colorectal Neoplasms; Motor Activity; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise
• Other Study ID Numbers: Exercise mCRC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No