GastroEsophageal Cancer, Incurable Disease
Conditions
Keywords
gastroesophageal cancer, GAC, Palliative, exercise intervention, nutritional intervention, Quality of life, QOL
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
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.
Interventions
OTHERExercise intervention
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.
OTHERNutrition intervention
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.
Sponsors
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
UMC Utrecht
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life (EORTC-QLQ-30) summary score | 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
| Measure | Time frame | Description |
|---|---|---|
| Aerobic capacity: MSEC | 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 |
| Muscle strength: Hand grip strength | 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. |
| Body composition: Muscle mass | Baseline, 12 weeks | Muscle mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-100 kg |
| Body composition: Fat mass | Baseline, 12 weeks | Fat mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 1-100 kg |
| Body composition: Weight | Baseline, 12 weeks | Weight will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-200 kg |
| Self-reported screening of malnutrition | 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 |
| Physical activity | 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. |
| WHO performance status | Baseline and during the intervention, until the end of the intervention (12 weeks). | Changes in WHO performance status. |
| Quality of life (EORTC-QLQ-30) total score | 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. |
| Self-reported screening of sarcopenia | Baseline,12 weeks | Changes in sarcopenia will be assessed using the Sarc-F questionnaire. (Scale 0-10, higher the score the better the condition). |
| Skeletal muscle index | Baseline, 12 weeks. | Changes in skeletal muscle index, assessed by diagnostic CT-scans. |
| Muscle strength: leg press maximal muscle strength | 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 |
| Medical effects: Treatment toxicity | 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 |
| Medical effects: percentage of patients starting second-line treatment | Baseline up to one year after intervention | Percentage of patients who have started second-line treatment |
| Medical effects: dose reductions | Baseline up to one year after intervention | Treatment tolerance assessed by the amount of delivered second-line systemic treatment doses. |
| Medical effects: dose delays | Baseline up to one year after intervention | Treatment tolerance assessed by the number of dose delays of second-line systemic treatment. |
| Medical effects: duration of systemic therapy | Baseline up to one year after intervention | Treatment tolerance assessed by the total duration of second-line systemic treatment. |
| Progression-free survival | Baseline up to one year after intervention | Time to progression |
| Overall survival | Baseline up to 1 year after intervention. | Proportion of patients who have not died 1 year after baseline. |
| Patient reported physical activity | 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. |
| Health-related quality of life: physical functioning | 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. |
| Health-related quality of life: role functioning | 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. |
| Health-related quality of life: fatigue | 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. |
Countries
Netherlands
Contacts
CONTACTAniek Bonhof, Msc
PRINCIPAL_INVESTIGATORHanneke van Laarhoven
Amsterdam AMC
Outcome results
None listed