Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| UMC Utrecht | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Usual Care | No Intervention | Patients randomized to the control group will receive standard medical care, including nutritional care as provided by the center in usual care. Additionally, they receive an activity tracker (like the intervention group) but without specific instructions. We will provide the control patients with written advice on physical activity and diet according to the current guidelines (in short: to avoid inactivity and be as physically active as current abilities and conditions allow, with the aim to progress towards being physically active for 150 min/week). | |
| Combined exercise and nutritional intervention. | Experimental | Intervention: exercise and nutrition program group |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Quality of life (EORTC-QLQ-30) summary score | 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). | Baseline, 6 weeks and every 12 weeks up to one year after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Aerobic capacity: MSEC | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| (Serious) Adverse Events potentially related to the exercise intervention | 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. |
Inclusion Criteria:
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aniek Bonhof, Msc | Contact | +31627437310 | A.Bonhof-3@umcutrecht.nl |
| Name | Affiliation | Role |
|---|---|---|
| Hanneke van Laarhoven | Amsterdam AMC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam UMC | Recruiting | Amsterdam | North Holland | 1081HV | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33837380 | Background | van Vulpen JK, Hiensch AE, van Hillegersberg R, Ruurda JP, Backx FJG, Nieuwenhuijzen GAP, Kouwenhoven EA, Groenendijk RPR, van der Peet DL, Hazebroek EJ, Rosman C, Wijnhoven BPL, van Berge Henegouwen MI, van Laarhoven HWM, Siersema PD, May AM. Supervised exercise after oesophageal cancer surgery: the PERFECT multicentre randomized clinical trial. Br J Surg. 2021 Jul 23;108(7):786-796. doi: 10.1093/bjs/znab078. | |
| 28821284 |
| Label | URL |
|---|---|
| national guidelines of the National Nutritionists Oncology Working Group (NNOWG; in Dutch: Landelijke Werkgroep Diëtisten Oncologie, LWDO) | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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. |
|
| Baseline, 12 weeks |
| Muscle strength: Hand grip strength | 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. | Baseline, 12 weeks |
| Body composition: Muscle mass | Muscle mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-100 kg | Baseline, 12 weeks |
| Body composition: Fat mass | Fat mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 1-100 kg | Baseline, 12 weeks |
| Body composition: Weight | Weight will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-200 kg | Baseline, 12 weeks |
| Self-reported screening of malnutrition | 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 | Baseline and every 12 weeks up to one year after intervention |
| Physical activity | 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. | Baseline, 12 weeks |
| WHO performance status | Changes in WHO performance status. | Baseline and during the intervention, until the end of the intervention (12 weeks). |
| Quality of life (EORTC-QLQ-30) total score | 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. | Baseline, 6 weeks and every 12 weeks up to one year after intervention |
| Self-reported screening of sarcopenia | Changes in sarcopenia will be assessed using the Sarc-F questionnaire. (Scale 0-10, higher the score the better the condition). | Baseline,12 weeks |
| Skeletal muscle index | Changes in skeletal muscle index, assessed by diagnostic CT-scans. | Baseline, 12 weeks. |
| Muscle strength: leg press maximal muscle strength | 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 | Baseline, 12 weeks |
| Medical effects: Treatment toxicity | 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 | Baseline up to one year after intervention |
| Medical effects: percentage of patients starting second-line treatment | Percentage of patients who have started second-line treatment | Baseline up to one year after intervention |
| Medical effects: dose reductions | Treatment tolerance assessed by the amount of delivered second-line systemic treatment doses. | Baseline up to one year after intervention |
| Medical effects: dose delays | Treatment tolerance assessed by the number of dose delays of second-line systemic treatment. | Baseline up to one year after intervention |
| Medical effects: duration of systemic therapy | Treatment tolerance assessed by the total duration of second-line systemic treatment. | Baseline up to one year after intervention |
| Progression-free survival | Time to progression | Baseline up to one year after intervention |
| Overall survival | Proportion of patients who have not died 1 year after baseline. | Baseline up to 1 year after intervention. |
| Patient reported physical activity | 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. | Baseline and every 12 weeks up to one year after intervention |
| Health-related quality of life: physical functioning | 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. | Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks). |
| Health-related quality of life: role functioning | 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. | Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks). |
| Health-related quality of life: fatigue | 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. | Baseline and every 2 weeks during the intervention, until the end of the intervention (12 weeks). |
| Baseline until the end of intervention (12 weeks) |
| Adherence and compliance to the exercise and diet intervention | 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. | During the intervention period of 12 weeks |
| Satisfaction with the exercise and nutritional intervention | 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. | Post-intervention (12 weeks) |
| UMC Utrecht | Recruiting | Utrecht | Utrecht | 3508GA | Netherlands |
|
| Jeroen Bosch Hospital | Active, not recruiting | 's-Hertogenbosch | Netherlands |
| Flevoziekenhuis | Recruiting | Almere Stad | Netherlands |
|
| Meander Medical Center | Not yet recruiting | Amersfoort | Netherlands |
|
| Reinier de Graaf | Recruiting | Delft | Netherlands |
|
| Catharina Ziekenhuis | Recruiting | Eindhoven | Netherlands |
|
| Beatrix Hospital | Recruiting | Gorinchem | Netherlands |
|
| Spaarne Gasthuis | Recruiting | Hoofddorp | Netherlands |
|
| Frisius Medical Center | Recruiting | Leeuwarden | Netherlands |
|
| Leiden Universitair Medisch Centrum | Recruiting | Leiden | Netherlands |
|
| Sint Antonius Hospital | Not yet recruiting | Nieuwegein | Netherlands |
|
| Canisius Wilhelmina Ziekenhuis | Recruiting | Nijmegen | Netherlands |
|
| RadboudUMC | Recruiting | Nijmegen | Netherlands |
|
| Laurentius Ziekenhuis | Recruiting | Roermond | Netherlands |
|
| Bravis Ziekenhuis | Recruiting | Roosendaal | Netherlands |
|
| Erasmus Medical Center | Recruiting | Rotterdam | Netherlands |
|
| Ikazia Ziekenhuis | Recruiting | Rotterdam | Netherlands |
|
| HagaZiekenhuis | Recruiting | The Hague | Netherlands |
|
| Elisabeth Tweesteden Hospital | Recruiting | Tilburg | Netherlands |
|
| Diakonessenhuis | Not yet recruiting | Utrecht | Netherlands |
| Zaans Medical Center | Recruiting | Zaandam | Netherlands |
|
| Background |
| van Vulpen JK, Siersema PD, van Hillegersberg R, Nieuwenhuijzen GAP, Kouwenhoven EA, Groenendijk RPR, van der Peet DL, Hazebroek EJ, Rosman C, Schippers CCG, Steenhagen E, Peeters PHM, May AM. Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial. BMC Cancer. 2017 Aug 18;17(1):552. doi: 10.1186/s12885-017-3542-8. |
| 35906659 | Background | Hiensch AE, Monninkhof EM, Schmidt ME, Zopf EM, Bolam KA, Aaronson NK, Belloso J, Bloch W, Clauss D, Depenbusch J, Lachowicz M, Pelaez M, Rundqvist H, Senkus E, Stuiver MM, Trevaskis M, Urruticoechea A, Rosenberger F, van der Wall E, de Wit GA, Zimmer P, Wengstrom Y, Steindorf K, May AM. Design of a multinational randomized controlled trial to assess the effects of structured and individualized exercise in patients with metastatic breast cancer on fatigue and quality of life: the EFFECT study. Trials. 2022 Jul 29;23(1):610. doi: 10.1186/s13063-022-06556-7. |
| 27637832 | Background | Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Fearon K, Hutterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Muhlebach S, Muscaritoli M, Oldervoll L, Ravasco P, Solheim T, Strasser F, de van der Schueren M, Preiser JC. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017 Feb;36(1):11-48. doi: 10.1016/j.clnu.2016.07.015. Epub 2016 Aug 6. |
| 31626055 | Background | Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019 Nov;51(11):2375-2390. doi: 10.1249/MSS.0000000000002116. |
| 26327487 | Background | Giesinger JM, Kieffer JM, Fayers PM, Groenvold M, Petersen MA, Scott NW, Sprangers MA, Velikova G, Aaronson NK; EORTC Quality of Life Group. Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust. J Clin Epidemiol. 2016 Jan;69:79-88. doi: 10.1016/j.jclinepi.2015.08.007. Epub 2015 Sep 28. |
| 35576506 | Background | Ligibel JA, Bohlke K, May AM, Clinton SK, Demark-Wahnefried W, Gilchrist SC, Irwin ML, Late M, Mansfield S, Marshall TF, Meyerhardt JA, Thomson CA, Wood WA, Alfano CM. Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline. J Clin Oncol. 2022 Aug 1;40(22):2491-2507. doi: 10.1200/JCO.22.00687. Epub 2022 May 16. |
| 41592243 | Derived | Bonhof A, Hiensch AE, Wierdsma NJ, Huis In 't Veld LF, Bakker SD, Beeker A, Davidis-van Schoonhoven M, Droogendijk H, Drooger JC, Douma JAJ, Goedegebuure RSA, Haj Mohammad N, van Hellemond IEG, Herbschleb K, Janssen JJB, Mostert B, Slingerland M, Sommeijer D, Timmermans L, Verschoor AJ, de Weger VA, Westdorp H, Wumkes ML, May AM, van Laarhoven HWM. Effects of exercise and diet in patients with incurable gastroesophageal cancer: the RADICES study. JNCI Cancer Spectr. 2026 Mar 3;10(2):pkag006. doi: 10.1093/jncics/pkag006. |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| ID | Term |
|---|---|
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
Not provided
Not provided