AzTrials
AzTrials

Colorectal CancerAMICONCT04754672

Aerobic Fitness or Muscle Mass Training to Improve Colorectal Cancer Outcome

A study testing Continuous aerobic and resistance exercise intervention and Continuous aerobic and aerobic interval exercise intervention in people with Colorectal Cancer and Chemotherapeutic Toxicity, run by Radboud University Medical Center at 13 sites in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Evidence from randomized controlled trials shows that exercise during cancer treatment benefits physical fitness, fatigue and quality of life. Since the effect of exercise on clinical outcome is currently unknown, exercise is not included as integral part of standard cancer care. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Continuous aerobic and resistance exercise intervention and Continuous aerobic and aerobic interval exercise intervention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
228 participants
Where
13 sitesNetherlands
Study dates
2 Mar 2021to Dec 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • mCRC with indication for palliative chemotherapy
  • scheduled for treatment with first-line doublet or triplet chemotherapy, according to the national guideline
  • able and willing to give written informed consent.

Who cannot join

  • life expectancy <6 months
  • unable to perform basic activities of daily living such as walking or biking
  • presence of cognitive disorders or severe emotional instability (e.g., Schizophrenia, Alzheimer, alcohol addiction);
  • presence of other disabling co-morbidities that might hamper physical exercise (e.g. heart failure (NYHA classes 3 and 4), chronic obstructive pulmonary disease (COPD, gold 3 and 4), orthopaedic conditions and neurological disorders (e.g., hernia, paresis, amputation, active rheumatoid arthritis);
  • insufficient mastery of the Dutch language;
  • presence of serious cardiovascular or cardiopulmonary conditions (e.g. unstable angina, arrhythmia or valve disease) such that exercise safety is at risk, as judged by the treating physician.
  • Already participating in structured vigorous aerobic and/or resistance exercise ≥ 2 times per week comparable to our intervention

Trial locations and contacts

13 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Laurien M Buffart, PhD contact

+31243613674

laurien.buffart@radboudumc.nl

13 sites in 1 country

Netherlands13 sites, 13 recruiting

  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5223 GZ

    M. Wumkes, MD

    M. Wumkes, MD

    Recruiting

  • Flevoziekenhuis

    Almere Stad, 1315 RA

    D. Sommeijer, MD

    D. Sommeijer, MD

    Recruiting

  • Meander Medisch Centrum

    Amersfoort, 3813TZ

    H.M. Otten, MD

    H.M. Otten, MD

    Recruiting

  • Ziekenhuis Amstelland

    Amstelveen, 1186AM

    A.A. v Zweeden, MD

    A.A. v Zweeden, MD

    Recruiting

  • Amsterdam UMC

    Amsterdam, 1007MB

    T.E. Buffart, MD

    T.E. Buffart, MD

    Recruiting

  • Netherlands Cancer Institute

    Amsterdam

    K. Bolhuis, MD

    K. Bolhuis, MD

    Recruiting

  • Rijnstate Ziekenhuis

    Arnhem, 6815 AD

    R. Koornstra, MD

    R. Koornstra, MD

    Recruiting

  • Ziekenhuis Amphia

    Breda, 4818CK

    M. Streppel, MD

    M. Streppel, MD

    Recruiting

  • Catharina Ziekenhuis

    Eindhoven, 5623 EJ

    G.J. Creemers, MD

    G.J. Creemers, MD

    Recruiting

  • Spaarne Gasthuis

    Hoofddorp, 2134TM

    A. Beeker, MD

    A. Beeker, MD

    Recruiting

  • Radboudumc

    Nijmegen, 6525GA

    L. Buffart, Dr.

    E. Gootjes, MD

    Recruiting

  • Canisius Wilhelmina Ziekenhuis

    Nijmegen, 6532SZ

    J.J.B. Janssen, MD

    J.J.B. Janssen, MD

    Recruiting

  • UMCU

    Utrecht, 3508GA

    A. May, Prof.

    J. Roodhart, Dr.

    Recruiting

Other trials in Netherlands

About this study

Official title: Aerobic Fitness or Muscle Mass Training to Improve Colorectal Cancer Outcome (AMICO). The Effects of Exercise on Chemotherapy Dose Modification and Progression Free Survival in Patients With Metastatic Colorectal Cancer

Evidence from randomized controlled trials shows that exercise during cancer treatment benefits physical fitness, fatigue and quality of life. Since the effect of exercise on clinical outcome is currently unknown, exercise is not included as integral part of standard cancer care. Moreover, evidence regarding the optimal exercise prescription in terms of type and dose is lacking.

To maintain quality of life in patients receiving palliative treatment with chemotherapy, toxicity-induced modifications in the prescribed chemotherapy dose are common. Such modifications - occurring in 40% of patients with metastatic colorectal cancer - may reduce benefit of treatment. The investigators hypothesize that exercise prevents chemotherapy dose modifications by reducing toxicity and enhancing psychological strength. Additionally, based on studies in rodents and preliminary data in patients with cancer, the researchers hypothesize that exercise has beneficial effects on the functionality of the natural killer cells, which play an important role in the innate immune defense against cancer. Both, fewer dose modifications and improved immune function may improve progression-free survival.

Read more

This study is a three-armed trial comparing resistance exercise, aerobic interval exercise and usual care in patients with metastatic colorectal cancer to select the optimal exercise prescription for preventing chemotherapy dose modifications. The trial will use a Bayesian adaptive multi-arm multi-stage design with several interim analyses after which an ineffective study arm can be dropped early. This novel design makes the trial more efficient and reduces patients' exposure to suboptimal study arms.

Evidence regarding the exercise effects on i) clinical outcome, ii) the optimal exercise prescription, and iii) the underlying mechanisms, elucidates the potential of exercise to boost benefit from chemotherapy treatment. This evidence provides leads to improve progression-free survival and quality of life of patients suffering from one of the leading causes of cancer death worldwide.

Read the detailed description

First-line treatment of metastatic colorectal cancer (mCRC) generally includes the chemotherapies fluoropyrimidines in combination with oxaliplatin and/or irinotecan, known as doublet or triplet chemotherapy. A previous study showed that over 40% of patients with metastatic colorectal cancer required dose modifications (including dose reductions, treatment delays or discontinuation) within the first three months of palliative treatment, and around 30% was admitted to hospital due to chemotherapy-related toxicity. Toxicity-induced dose modifications and hospitalization may reduce benefit of treatment. In patients with metastatic colorectal cancer, reductions in muscle mass and lower physical activity levels (<9 metabolic equivalent of task hours/week) were found to be associated with more dose-limiting toxicity and shorter (progression-free) survival. However, the causality and underlying mechanisms linking physical activity and exercise to cancer outcome have not been elucidated. The immune system (by increased infiltration of activated natural killer cells into the tumour) might play a role as was shown in studies with rodents. In addition, studies among patients showed that exercise may counteract a variety of treatment toxicities (e.g. neutropenia, neuropathy, gastrointestinal side effects, fatigue), but optimal exercise type and dose are unknown.

In addition to the above-mentioned biophysiological effects by which exercise may prevent dose modifications, several studies demonstrated the positive effects of exercise during cancer treatment on quality of life. A recent study on patients' perceptions indicated that exercise helped patients to better cope with cancer treatments, as it gave them psychological strength (i.e. empowerment and resilience) next to physical strength. The investigators hypothesize that exercise reduces treatment-related toxicity and thereby reduces chemotherapy dose modifications and improves progression free survival.

randomised controlled trials are the gold standard for ascertaining treatment efficacy. Studying differences in effects on chemotherapy dose modifications between different exercise programs requires a multi-arm randomised controlled trial. Due to complex logistics and high costs, the conduct of a traditional adequately powered multi-arm exercise trial is difficult with available patients and resources. Therefore, a Bayesian adaptive flexible multi-arm multi-stage design will be used which allows for a number of interim analyses after which a treatment arm can be dropped early if it falls outside the pre-defined futility/efficacy boundaries. This reduces patients' exposure to suboptimal interventions and increases trial efficiency.

This study aims to examine whether:

  1. Exercise prevents chemotherapy dose modifications via reduced toxicity and enhanced psychological strength, and which exercise program yields largest benefits.
  2. Exercise improves immune function (e.g. functionality of natural killer cells).
  3. Benefits of exercise on dose modifications and immune function improves progression-free survival.
Being tested
Continuous aerobic and resistance exercise intervention, Continuous aerobic and aerobic interval exercise intervention
Keywords
Exercise, Muscle strength, Cardiorespiratory fitness, Colorectal cancer, Chemotherapy dose modification, Progression free survival, Bayesian adaptive trial
Medical subject headings
Colorectal Neoplasms, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Continuous aerobic and resistance exercise interventionBehavioural

    Also called AE+RE

    Continuous aerobic and resistance exercises intervention

  • Continuous aerobic and aerobic interval exercise interventionBehavioural

    Also called AE+AI

    Continuous aerobic and aerobic interval exercise intervention

Study groups in NCT04754672
Study groupRoleWhat they receive
Continuous aerobic and resistance exercise (AE+RE)ExperimentalTwo 60 min moderate-to-high intensity exercise sessions per week supervised by a physiotherapist. Continuous aerobic exercise: 15-20 min continuous aerobic exercise (e.g. walking) of moderate intensity (Borg 13-14 'somewhat hard'). Resistance exercise (25 min): 6 exercises targeting large muscle groups vertical row, squat, bench press, pull over, abdominal crunch, and lunge. 2 sets of 10 repetitions at 70-80% of 1 RM. To ensure adequate training load over time, tests are repeated every 3/4 weeks aligned with the chemotherapy cycle. One additional (third) session from home at moderate intensity for at least 30 min. A brochure with exercise guidelines is provided.
Receives: Behavioral: Continuous aerobic and resistance exercise intervention
Continuous aerobic and aerobic interval exercise (AE+AI)ExperimentalContinuous aerobic exercise: 15-20 min continuous aerobic exercise (e.g. walking) of moderate intensity (Borg 13-14 'somewhat hard'). Aerobic interval (25 min): cycling with high intensity intervals alternated with recovery intervals. Intensity of the interval: between 85% and 95% of estimated maximum heart rate, adjusted to Borg 16-18 'hard - very hard'. In between the intervals, light intensity cycling will be performed for active recovery at 30% of Wmax estimated from Steep ramp test and adjusted to Borg < 12. One additional (third) session from home at moderate intensity for at least 30 min. A brochure with exercise guidelines is provided.
Receives: Behavioral: Continuous aerobic and aerobic interval exercise intervention
Usual care control groupNo interventionPatients in the usual care group receive care as usual. In addition, a brochure with exercise guidelines for cancer survivors is provided

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Chemotherapy dose modifications

    Number of patients requiring dose modifications (i.e. dose reductions, treatment delay, discontinuation or switch)

    Measured: between baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch. Cycle duration is 2 or 3 weeks.

  2. Progression free survival

    From date of randomization until the date of first documented progression

    Measured: between baseline and time to progression (up to 2 years)

Secondary outcomes (12)

  1. NK-cell functionality

    degranulation and cytotoxicity of NK-cells on peripheral blood mononuclear cells

    Measured: change from baseline to 6th treatment cycle or treatment switch (Cycle duration is 3 weeks)

  2. Hospitalization

    Number of patients requiring hospitalisation assessed from medical records

    Measured: during treatment (6 treatment cycles of 3 weeks per cycle or 8 treatment cycles of 2 weeks per cycle)

  3. Treatment-related toxicity

    severity of treatment-related toxicity assessed with the Common Terminology Criteria for Adverse Events

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  4. Aerobic fitness

    Astrand-Rhyming test

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  5. Maximum short exercise capacity

    Steep ramp test

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  6. Muscle strength

    indirect 1 repetition maximum for leg press

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  7. Muscle mass

    Computed Tomogrophy scans

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  8. Health-related quality of life

    European Organization for Research and Treatment of Cancer Quality of Life Questionaire Core 30. Score from 0-100, higher scores indicate better functioning

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  9. Fatigue

    European Organization for Research and Treatment of Cancer Quality of Life Questionaire- Fatigue 12. Score 0-100, higher scores indicate higher levels of fatigue

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  10. Resilience

    Resilience Evaluation Scale, score 0-40, higher scores indicate better resilience

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  11. Empowerment

    Self-efficacy-28, score 4-28, higher scores indicate better empowerment

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

  12. Physical activity

    Short QUestionnaire to ASsess Health enhancing physical activity, higher scores indicate higher physical activity levels

    Measured: change from baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch (cycle duration is 2 or 3 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2021
  2. Study start2 Mar 2021
  3. Primary completionMar 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomised controlled trial
Masking
None (open label)
Enrolment
228 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04754672
Sponsor's protocol ID
2020-6867
Other IDs
NL72482.091.20, 09150171910017
Acronym
AMICO
Status last verified
Nov 2023
First submitted
4 Dec 2020
Last updated
18 Nov 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD will be shared via the POLARIS consortium see PROSPERO registry CRD42013003805 or paper: Buffart et al. Systematic Reviews 2013; 2: 75.

Publications

  • Brouwer CG, Tusscher MRT, de Roos BM, Gootjes EC, Buffart TE, Versteeg KS, Mast IH, Streppel MM, Werter IM, May AM, Verheul HMW, Buffart LM; AMICO Consortium. Experiences of patients with metastatic colorectal cancer participating in a supervised exercise intervention during chemotherapy. Support Care Cancer. 2025 Jan 8;33(2):82. doi: 10.1007/s00520-024-09101-1.

    PubMed 39779537

Questions about this trial

What is this clinical trial studying?

A study testing Continuous aerobic and resistance exercise intervention and Continuous aerobic and aerobic interval exercise intervention in people with Colorectal Cancer and Chemotherapeutic Toxicity, run by Radboud University Medical Center at 13 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Laurien M Buffart, PhD (+31243613674, laurien.buffart@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Chemotherapy dose modifications (time frame: between baseline to 3rd/4th and 6th/8th treatment cycle or treatment switch. Cycle duration is 2 or 3 weeks.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04754672, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in