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NCT Number: NCT06138223

The Effect of exeRcise And Diet on Quality of Life in Patients With Incurable Cancer of Esophagus and Stomach (RADICES)

The survival of patients with incurable gastroesophageal cancer can extend over a year with anticancer therapy. However, the number of patients with deteriorating quality of life in this patient group steadily decreases over time during the treatment. Potentially reversible causes related to deterioration of quality of life are diminished muscle mass, physical capacity and nutritional status. Therefore, interventions that can target these in order to maintain or improve quality of life are urgently needed.

However, it is yet unknown whether improvement of physical capacity and nutritional status improves quality of life in patients with incurable gastroesophageal adenocarcinoma after failure of first-line treatment. Since these patients are in a precarious situation, the benefits and harms of a combined exercise and nutritional intervention should be carefully evaluated.Therefore this study investigates the effect of a combined exercise and nutrition intervention compared to usual care on quality of life in incurable GAC patients after progression upon first-line treatment.

A total of 196 patients with metastasized gastroesophageal cancer will be recruited and randomly allocated 1:1 to standard care or standard care plus a combined exercise and nutritional intervention.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Amsterdam UMC, Amsterdam, North Holland, Netherlands

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About this study

After one year of recruitment we broadened our inclusion criteria from GAC patients receiving beyond first-line palliative treatment or best supportive care to any patient with recurrence/progression of GAC after curative treatment or irresectable/metastatic disease at diagnosis, regardless of timing or type of palliative treatment and number of lines received. Accordingly, we had to alter stratification. The first 23 patients were stratified by: duration of first-line therapy (shorter or longer than 6 months), WHO performance status (0, 1, 2), and intended start of second-line systemic therapy (yes or no). After broadening the criteria, stratification factors were changed to: WHO performance status (0 versus ≥1) and treatment line (first versus second/higher/best supportive care).

Due to the nature of the intervention, it is not possible to blind the patients, the local study nurses, or the investigators to the treatment assignment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Incurable adenocarcinoma of the esophagus or stomach
  • Recurrence after treatment with curative intent or irresectable/metastatic disease at primary diagnosis. Inclusion can take place regardless of the plan or the actual initiation of multi-line systemic treatment. (i.e. patients that have already started with anticancer therapy are eligible for inclusion too)*
  • Able and willing to perform the exercise and nutritional program and wear the activity tracker.
  • Able and willing to fill out the POCOP/RADICES questionnaires.
  • Life expectancy > 12 weeks.
  • Age ≥ 18 years.

Exclusion criteria

  • Unstable bone metastases inducing skeletal fragility as determined by the treating clinician.
  • Untreated symptomatic known brain metastasis.
  • Serious active infection.
  • Too physically active (i.e. >210 minutes/week of moderate-to-vigorous intentional exercise) or engaging in intense exercise training comparable to the RADICES exercise program.
  • Severe neurologic or cardiac impairment according to the American College of Sports Medicine criteria.
  • Uncontrolled severe respiratory insufficiency as determined by the treating clinician or if the patient is dependent on oxygen suppletion in rest or during exercise.
  • Uncontrolled severe pain.
  • Any other contraindications for exercise as determined by the treating physician.
  • Any circumstances that would impede adherence to study requirements or ability to give informed consent, as determined by the treating clinician.
  • Pregnancy.
  • Note:

After one year of recruitment we broadened our inclusion criteria from GAC patients receiving beyond first-line palliative treatment or best supportive care to any patient with recurrence/progression of GAC after curative treatment or irresectable/metastatic disease at diagnosis, regardless of timing or type of palliative treatment and number of lines received. This was done to increase generalizability and offer the intervention earlier in the palliative phase to enhance its benefits. We acknowledge this results in a more heterogeneous group, but we believe also a more representative group.

The inclusion criterium before broadening was:

Progressive disease after first-line palliative systemic treatment OR within 6 months after completion of curative treatment (i.e. within six months after neoadjuvant chemoradiation, adjuvant nivolumab, or definitive chemoradiation for esophageal adenocarcinoma or within six months after adjuvant 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) for gastric/esophageal cancer or neoadjuvant FLOT if no adjuvant FLOT was given, or after progression during participation in the LyRICX study). Patients on capecitabine monotherapy who are eligible for oxaliplatin reintroduction can be included, too.

Treatment and study plan

Exercise intervention

Other

During 12 weeks, patients will visit twice a week a trained oncology physiotherapist for one hour per session. This training includes supervised aerobic and resistance exercises to increase aerobic condition and muscle resistance, based on their own fitness level as assessed at baseline. Additionally, physiotherapists will educate participants on how to increase their daily activity. To this end, all participants will receive an activity tracker to monitor their daily activities.

Nutrition Intervention

Other

Once every two weeks patients in the intervention group will receive a nutritional assessment and intervention by a trained dietician for optimization of their nutritional intake to improve their nutritional status, following the ESPEN guideline on nutrition in cancer patients and the national guidelines of the National Nutritionists Oncology Working Group (NNOWG; in Dutch: Landelijke Werkgroep Diëtisten Oncologie, LWDO). Moreover, an amount of 15-25 grams of protein within 1-2 hours after exercise will be advised, to prevent muscle protein breakdown and enhance muscle protein synthesis.

Primary outcomes

  1. Quality of life (EORTC-QLQ-30) summary score

    Time frame: Baseline, 6 weeks and every 12 weeks up to one year after intervention

    European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item. The summary score encompasses the last question of this questionnaire.

    Scale: 1-7 Higher score means better quality of life.

    Analyzed will be the difference in quality of life between the intervention group and the control group at 12 weeks, taking into account the baseline values, and measured with the Summary Score of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

Secondary outcomes

  1. Aerobic capacity: MSEC

    Time frame: Baseline, 12 weeks

    Changes in MSEC (= maximum short exercise capacity or in other words maximum wattage in the steep ramp test).

    In the steep ramp test participants cycle with a pedal frequency between 70 and 80 rpm 30 seconds at 25 W. Then every 10 seconds, the load is increased with 25 W until exhaustion. The test ends when pedal frequency falls below 60 rpm. From the MSEC peak Wattage (Wpeak) can be estimated using a regression equation.

    Scale: 0-500 W

  2. Muscle strength: Hand grip strength

    Time frame: Baseline, 12 weeks

    Changes in hand grip strength. Hand grip strength: using a handgrip dynamometer the participant will be asked to squeeze the dynamometer as hard as possible for three times, for both hands. The best of three attempts for bot hands is recorded.

    Scale: 0-100 kg.

  3. Body composition: Muscle mass

    Time frame: Baseline, 12 weeks

    Muscle mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-100 kg

  4. Body composition: Fat mass

    Time frame: Baseline, 12 weeks

    Fat mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 1-100 kg

  5. Body composition: Weight

    Time frame: Baseline, 12 weeks

    Weight will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-200 kg

  6. Self-reported screening of malnutrition

    Time frame: Baseline and every 12 weeks up to one year after intervention

    Malnutrition will be screened using the short-form Abridged Scored Patient-Generated Subjective Global Assessment (abPG-SGA).

    Scale: 0-50 Higher score is more malnourished

  7. Physical activity

    Time frame: Baseline, 12 weeks

    Physical activity is measured by an activity tracker (Fitbit). Participants are instructed to wear the tracker for 12 weeks. Mean daily steps and minutes spent in different intensity levels of physical activity are calculated, excluding no-wear days.

  8. WHO performance status

    Time frame: Baseline and during the intervention, until the end of the intervention (12 weeks).

    Changes in WHO performance status.

  9. Quality of life (EORTC-QLQ-30) total score

    Time frame: Baseline, 6 weeks and every 12 weeks up to one year after intervention

    European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item.

    Changes in total quality of life. Scale: 0-100 Higher score means better quality of life.

  10. Self-reported screening of sarcopenia

    Time frame: Baseline,12 weeks

    Changes in sarcopenia will be assessed using the Sarc-F questionnaire. (Scale 0-10, higher the score the better the condition).

  11. Skeletal muscle index

    Time frame: Baseline, 12 weeks.

    Changes in skeletal muscle index, assessed by diagnostic CT-scans.

  12. Muscle strength: leg press maximal muscle strength

    Time frame: Baseline, 12 weeks

    Changes in leg press one repetition maximum (1RM). Leg strength: the 12 repetition maximum is the maximum weight with which exactly 12 repetitions of a defined exercise/movement sequence can be performed with clean technique. Afterwards, the so called hypothetical 1RM (h1RM) can be calculated.

    Scale: 0-200 kg

  13. Medical effects: Treatment toxicity

    Time frame: Baseline up to one year after intervention

    Changes in treatment toxicity in case of start of second line systemic treatment will be assessed using the Common Terminology Criteria for Adverse Events version 5.0

  14. Medical effects: percentage of patients starting second-line treatment

    Time frame: Baseline up to one year after intervention

    Percentage of patients who have started second-line treatment

  15. Medical effects: dose reductions

    Time frame: Baseline up to one year after intervention

    Treatment tolerance assessed by the amount of delivered second-line systemic treatment doses.

  16. Medical effects: dose delays

    Time frame: Baseline up to one year after intervention

    Treatment tolerance assessed by the number of dose delays of second-line systemic treatment.

  17. Medical effects: duration of systemic therapy

    Time frame: Baseline up to one year after intervention

    Treatment tolerance assessed by the total duration of second-line systemic treatment.

  18. Progression-free survival

    Time frame: Baseline up to one year after intervention

    Time to progression

  19. Overall survival

    Time frame: Baseline up to 1 year after intervention.

    Proportion of patients who have not died 1 year after baseline.

  20. Patient reported physical activity

    Time frame: Baseline and every 12 weeks up to one year after intervention

    Physical activity will be assessed by the validated and reliable Short Questionnaire to assess health enhancing physical activity (SQUASH) including commuting activities, leisure time activities, household activities, and activities at work and school.

  21. Health-related quality of life: physical functioning

    Time frame: Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks).

    Changes in physical functioning, element of the EORTC-QLQ-30. To improve measurement precision compared to the standard, static EORTC-QLQ-C30 questionnaire, and to avoid floor- and ceiling effects, physical functioning will be assessed using computer adaptive testing in collaboration with experts of the EORTC.

  22. Health-related quality of life: role functioning

    Time frame: Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks).

    Changes in role functioning, element of the EORTC-QLQ-30. To improve measurement precision compared to the standard, static EORTC-QLQ-C30 questionnaire, and to avoid floor- and ceiling effects, role functioning will be assessed using computer adaptive testing in collaboration with experts of the EORTC.

  23. Health-related quality of life: fatigue

    Time frame: Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks).

    Changes in fatigue, element of the EORTC-QLQ-30. To improve measurement precision compared to the standard, static EORTC-QLQ-C30 questionnaire, and to avoid floor- and ceiling effects, fatigue will be assessed using computer adaptive testing in collaboration with experts of the EORTC.

Other outcomes

  1. (Serious) Adverse Events potentially related to the exercise intervention

    Time frame: Baseline until the end of intervention (12 weeks)

    Adverse events will be monitored and reported according to the Exercise Harms Reporting Method (ExHaRM). Patients in both groups will be asked by the study team about adverse events systematically and in a standardized manner at the follow-up measurement. Patients will be asked by their trainer before and after each supervised session whether any (Serious) Adverse Events occurred during or since the last session (i.e. active surveillance). In addition, trainers will be asked to actively observe for adverse events that may occur during training sessions as well (i.e. passive surveillance). An adverse event panel, consisting of independent exercise and nutritional professionals and clinicians, will review all adverse event forms and determine whether adverse events are indeed potentially causally related to the exercise or nutritional intervention or not.

  2. Adherence and compliance to the exercise and diet intervention

    Time frame: During the intervention period of 12 weeks

    Session attendance and adherence to the planned exercise dose/session. Deviations from the scheduled exercise dose are recorded by the physiotherapist. Attendance rates are computed as the number of supervised exercise sessions attended divided by the number of sessions prescribed and as the number of sessions with the dietician attended divided by the number of sessions prescribed. Compliance will be calculated for the exercise part as the ratio of total completed to total planned cumulative dose for three parts of the RADICES exercise program: duration of aerobic exercises, intensity of aerobic exercises and muscle strength exercises. Compliance will be calculated for the nutritional part as the ratio of total completed to total planned intake of calories, proteins and fat.

  3. Satisfaction with the exercise and nutritional intervention

    Time frame: Post-intervention (12 weeks)

    Intervention group only. After the 12-week intervention period, we will assess satisfaction with the exercise and nutritional intervention by means of a self-designed questionnaire. The questionnaire contains satisfaction items with regard to the supervised exercise program, the trainer, the activity tracker and the nutritional intervention.

Study contacts

Contact information is provided by the study sponsor or research team.

Aniek Bonhof, Msc

CONTACT

[email protected]

+31627437310

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Collaborators

  • UMC Utrecht

Registry information

Acronym: RADICES

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Nov 18, 2023
Registry last updated
May 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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