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

Not Applicable
Recruiting
Conditions
GastroEsophageal Cancer
Incurable Disease
Interventions
Other: Exercise intervention
Other: Nutrition intervention
Registration Number
NCT06138223
Lead Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Brief Summary

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.

Detailed Description

Randomization will be stratified based on: duration of first line therapy (shorter or longer than 6 months), WHO performance status (0, 1 versus 2), (intended) start of second-line (or further) systemic therapy for progressive disease (yes versus no) and time since failure of first line therapy (shorter or longer than 3 months ago). 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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
196
Inclusion Criteria
  • Incurable adenocarcinoma of the esophagus or stomach.
  • 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. 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 second/third/etc. line 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Combined exercise and nutritional intervention.Exercise interventionIntervention: exercise and nutrition program group
Combined exercise and nutritional intervention.Nutrition interventionIntervention: exercise and nutrition program group
Primary Outcome Measures
NameTimeMethod
Quality of life (EORTC-QLQ-30) summary scoreBaseline, 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 Outcome Measures
NameTimeMethod
Skeletal muscle indexBaseline, 12 weeks.

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

Body composition: Fat massBaseline, 12 weeks

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

Aerobic capacity: MSECBaseline, 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

Body composition: Muscle massBaseline, 12 weeks

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

Physical activityBaseline, 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.

Medical effects: dose reductionsBaseline up to one year after intervention

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

Medical effects: duration of systemic therapyBaseline up to one year after intervention

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

Quality of life (EORTC-QLQ-30) total scoreBaseline, 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.

Muscle strength: leg press maximal muscle strengthBaseline, 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

Medical effects: Treatment toxicityBaseline 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

Muscle strength: Hand grip strengthBaseline, 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.

Body composition: WeightBaseline, 12 weeks

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

Self-reported screening of sarcopeniaBaseline,12 weeks

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

Medical effects: dose delaysBaseline up to one year after intervention

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

Progression-free survivalBaseline up to one year after intervention

Time to progression

Self-reported screening of malnutritionBaseline 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

WHO performance statusBaseline and during the intervention, until the end of the intervention (12 weeks).

Changes in WHO performance status.

Medical effects: percentage of patients starting second-line treatmentBaseline up to one year after intervention

Percentage of patients who have started second-line treatment

Patient reported physical activityBaseline 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.

Health-related quality of life: physical functioningBaseline 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.

Health-related quality of life: role functioningBaseline 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.

Overall survivalBaseline up to 1 year after intervention.

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

Health-related quality of life: fatigueBaseline 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.

Trial Locations

Locations (12)

Amsterdam UMC

🇳🇱

Amsterdam, Noord-Holland, Netherlands

Reinier de Graaf

🇳🇱

Delft, Netherlands

Catharina Ziekenhuis

🇳🇱

Eindhoven, Netherlands

HagaZiekenhuis

🇳🇱

Den Haag, Netherlands

Medisch Centrum Leeuwarden

🇳🇱

Leeuwarden, Netherlands

Canisius Wilhelmina Ziekenhuis

🇳🇱

Nijmegen, Netherlands

Spaarne Gasthuis

🇳🇱

Hoofddorp, Netherlands

Leiden Universitair Medisch Centrum

🇳🇱

Leiden, Netherlands

Bravis Ziekenhuis

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Roosendaal, Netherlands

Laurentius Ziekenhuis

🇳🇱

Roermond, Netherlands

Ikazia Ziekenhuis

🇳🇱

Rotterdam, Netherlands

UMC Utrecht

🇳🇱

Utrecht, Netherlands

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