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

GastroEsophageal Cancer Clinical Trial

— RADICES  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06138223
• Other study ID #: NL83835.018.23
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 1, 2023
• Est. completion date: September 30, 2028

Study information

• Verified date: November 2023
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 196
• Est. completion date: September 30, 2028
• Est. primary completion date: September 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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). Patients on capecitabine monotherapy who are eligible for oxaliplatin reintroduction can be included, 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.
• 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.

Related Conditions & MeSH terms

• Esophageal Neoplasms
• GastroEsophageal Cancer
• Incurable Disease

Intervention

Other:
• Exercise 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.
• Nutrition 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).

Locations

Country	Name	City	State
Netherlands	Amsterdam UMC	Amsterdam	Noord-Holland
Netherlands	UMC Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	(Serious) Adverse Events potentially related to the exercise intervention	Intervention group only. SAE will be recorded during trial visits and through medical records. This procedure will concern SAE's potentially related to the exercise intervention during the trial period.	Baseline until the end of intervention (12 weeks)
Primary	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
Secondary	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	Baseline, 12 weeks
Secondary	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
Secondary	Body composition: Muscle mass	Muscle mass will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-100 kg	Baseline, 12 weeks
Secondary	Body composition: Weight	Weight will be measured with the validated InBody Dial H20B Smart Scale. Scale: 0-500 kg	Baseline, 12 weeks
Secondary	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
Secondary	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
Secondary	WHO performance status	Changes in WHO performance status.	Baseline and during the intervention, until the end of the intervention (12 weeks).
Secondary	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
Secondary	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
Secondary	Skeletal muscle index	Changes in skeletal muscle index, assessed by diagnostic CT-scans.	Baseline, 12 weeks.
Secondary	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
Secondary	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
Secondary	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
Secondary	Medical effects: dose reductions	Treatment tolerance assessed by the amount of delivered second-line systemic treatment doses.	Baseline up to one year after intervention
Secondary	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
Secondary	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
Secondary	Progression-free survival	Time to progression	Baseline up to one year after intervention
Secondary	Overall survival	Proportion of patients who have not died 1 year after baseline.	Baseline up to 1 year after intervention.
Secondary	Patient reported physical activity	Changes in patient-reported physical activity as assessed by the Short Questionnaire to assess health enhancing physical activity (SQUASH).	Baseline and every 12 weeks up to one year after intervention
Secondary	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).
Secondary	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).
Secondary	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).

External Links

•   national guidelines of the National Nutritionists Oncology Working Group (NNOWG; in Dutch: Landelijke Werkgroep Diëtisten Oncologie, LWDO)