Phase 2 pilot-study: to examine feasible exercise dosages in patients with mCRC and collect data on preliminary effects on clinical outcomes.Phase 3 trial: to collect data on the efficacy of exercise on 1) chemotherapy dose modifications and 2)…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 2 (feasbility):
1. recruitment
2. adherence and compliance
3. participant*s and counsellors satisfaction, perceived facilitators and
barriers for implementation
4. contamination
5. adverse events
Phase 3 (effects):
1. Chemotherapy dose modifications (dose reductions, treatment delay,
discontinuation or switch)
2. Progression free survival (PFS)
Secondary outcome
Both phase 2 & 3:
1. clinical data
-treatment-related toxicity
-treatment modifications (dose reductions, treatment delay,
discontinuation, or switch) / primary outcome in phase 3 trial
-hospitalization
2. aerobic fitness
3. Immune function
4. muscle strength and mass
5. physical activity (objective and self-report)
6. physical performance (age > 70)
7. Patient reported outcomes: HRQoL, symptoms related to mCRC and its
treatment, resilience and self-efficacy.
8. Demographic and clinical covariables (tumor stage and location, ECOG,
nutritional status)
Background summary
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. In a previous study, we
found that over 40% of patients with mCRC required dose modifications
(including dose reductions, treatment delays or discontinuation) within the
first three months of chemotherapy 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 mCRC, reductions in muscle mass and lower physical activity levels (<9 MET
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
NK-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. We hypothesize that
exercise reduces treatment-related toxicity and thereby reduces chemotherapy
dose modifications and improves progression free survival (PFS). In order to
conduct a sufficiently powered phase 3 randomized controlled trial (RCT) to
examine the effects of exercise on chemotherapy dose modifications, it is
essential to determine feasible dosages of resistance and aerobic exercise in
patients with mCRC during a phase 2 trial. Studying differences in effects on
chemotherapy dose modifications between different exercise programs requires a
multi*arm RCT. 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, we will use a Bayesian adaptive
flexible multi*arm multi*stage (MAMS) design 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.
Study objective
Phase 2 pilot-study: to examine feasible exercise dosages in patients with mCRC
and collect data on preliminary effects on clinical outcomes.
Phase 3 trial: to collect data on the efficacy of exercise on 1) chemotherapy
dose modifications and 2) progression free survival (PFS).
Study design
Multicenter randomized controlled phase 2 and 3 trial
Intervention
Participants will be randomized into one of three study arms: 1) Continuous
aerobic exercise (moderate intensity) combined with resistance exercise aiming
to maintain muscle mass for 60 minutes twice a week; 2) Continuous aerobic
exercise (moderate intensity) combined with high-intensity aerobic interval
exercise aiming to maintain aerobic fitness for 60 minutes twice a week; and 3)
a usual care control group that receives usual care. Both intervention groups
will be asked to be physically active an additional third time a week (for at
least 30 min with moderate intensity) on their own according to the American
College of Sports Medicine (ACSM) guidelines [26].
The intervention starts with the first cycle of chemotherapy and will continue
until the end of the sixth cycle (3-week cycle) or the eight cycle (2-week
cycle). After completion, 3 sessions will be offered to guide self-management
to maintain exercise levels on their own. Patients from both intervention
groups will be asked to stay physically active for 3 times a week and to keep
doing the same sort of exercises as prescribed in the first period (T0-T2),
i.e., resistance versus aerobic interval exercises. The intervention ends
after 27 weeks or ends in case of disease progression or treatment switch to
second line.
All groups receive a brochure with exercise guidelines based on the American
College of Sports Medicine*s (ACSM) cancer-specific exercise recommendations
[26].
Study burden and risks
Patients randomized to the exercise group will be guided by an physical
therapist that is educated specifically on the exercise protocol for this study
and are used to working with oncology patients. Therefore we expect a
negligible risk for participants with regard to the exercises. Previously
conducted exercise studies in advanced cancer patients appeared to be safe,
with no serious adverse events reported. Patients will be screened before the
physical fitness tests in the hospital on medical history which could interfere
with the physical fitness tests. Therefore we expect negligible risk for
participants with regard to the physical fitness tests and blood drawing. We
hypothesize that the intervention is feasible. If effective, the intervention
may result in less treatment-related toxicity, less chemotherapy dose
modifications and increased PFS.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
-age >=18 years;
-mCRC with indication for chemotherapy, with initially unresectable metastatic
disease
-scheduled for treatment with first-line doublet or triplet chemotherapy,
according to the national guideline
-able and willing to give written informed consent.
Exclusion criteria
-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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04754672 |
| CCMO | NL72482.091.20 |