Aerobic Fitness or Muscle Mass Training to Improve Colorectal Cancer Outcome

NCT04754672 | Recruiting DMC

• 3 other identifiers: 2020-6867NL72482.091.2009150171910017
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 13

Brief 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. 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. 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.

Conditions

Colorectal Cancer; Chemotherapeutic Toxicity; Survivorship; Lifestyle

Keywords

Exercise; Muscle strength; Cardiorespiratory fitness; Colorectal cancer; Chemotherapy dose modification; Progression free survival; Bayesian adaptive trial

Outcome Measures

Primary Outcomes (2)

• Chemotherapy dose modifications

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

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

• Progression free survival

  From date of randomization until the date of first documented progression

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

Secondary Outcomes (12)

• NK-cell functionality

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

• Hospitalization

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

• Treatment-related toxicity

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

• Aerobic fitness

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

• Maximum short exercise capacity

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

Study Arms (3)

Continuous aerobic and resistance exercise (AE+RE)

EXPERIMENTAL

Two 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.

Behavioral: Continuous aerobic and resistance exercise intervention

Continuous aerobic and aerobic interval exercise (AE+AI)

EXPERIMENTAL

Continuous 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.

Behavioral: Continuous aerobic and aerobic interval exercise intervention

Usual care control group

NO INTERVENTION

Patients in the usual care group receive care as usual. In addition, a brochure with exercise guidelines for cancer survivors is provided

Interventions

Continuous aerobic and resistance exercise intervention BEHAVIORAL

Continuous aerobic and resistance exercises intervention

Also known as: AE+RE

Continuous aerobic and resistance exercise (AE+RE)

Continuous aerobic and aerobic interval exercise intervention BEHAVIORAL

Continuous aerobic and aerobic interval exercise intervention

Also known as: AE+AI

Continuous aerobic and aerobic interval exercise (AE+AI)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• UMC Utrecht: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Rijnstate Hospital: collaborator
• Jeroen Bosch Ziekenhuis: collaborator
• Flevoziekenhuis: collaborator
• Catharina Ziekenhuis Eindhoven: collaborator
• Meander Medical Center: collaborator
• Ziekenhuis Amstelland: collaborator
• Amphia Hospital: collaborator
• Spaarne Gasthuis: collaborator
• Canisius-Wilhelmina Hospital: collaborator
• Amsterdam UMC, location VUmc: collaborator
• The Netherlands Cancer Institute: collaborator

Study Sites (13)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

RECRUITING

Flevoziekenhuis

Almere Stad, 1315 RA, Netherlands

RECRUITING

Meander Medisch Centrum

Amersfoort, 3813TZ, Netherlands

RECRUITING

Ziekenhuis Amstelland

Amstelveen, 1186AM, Netherlands

RECRUITING

Amsterdam UMC

Amsterdam, 1007MB, Netherlands

RECRUITING

Netherlands Cancer Institute

Amsterdam, Netherlands

RECRUITING

Rijnstate Ziekenhuis

Arnhem, 6815 AD, Netherlands

RECRUITING

Ziekenhuis Amphia

Breda, 4818CK, Netherlands

RECRUITING

Catharina Ziekenhuis

Eindhoven, 5623 EJ, Netherlands

RECRUITING

Spaarne Gasthuis

Hoofddorp, 2134TM, Netherlands

RECRUITING

Radboudumc

Nijmegen, 6525GA, Netherlands

RECRUITING

Canisius Wilhelmina Ziekenhuis

Nijmegen, 6532SZ, Netherlands

RECRUITING

UMCU

Utrecht, 3508GA, Netherlands

RECRUITING

Related Publications (1)

• 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.

  PMID: 39779537 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Motor Activity

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Behavior

Central Study Contacts

Laurien M Buffart, PhD

CONTACT

+31243613674; laurien.buffart@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Treatment allocation is concealed. Baseline assessments prior to group allocation.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised controlled trial

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: February 15, 2021
• Study Start: March 2, 2021
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share

Locations

NL (13)