Clinical trial NCT04789694: Prehabilitation in Gynaecological Cancer Patients
Official title: Prehabilitation in Patients With Gynaecological Cancer Planned for Postponed Surgical Management: A Prospective Randomised Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ovarian Cancer
Ovarian Cancer Stage III
Ovarian Cancer Stage IV
Endometrial Cancer
Frailty
Keywords: Prehabilitation
Epitelial ovarian cancer
Functional capacity
Quality of life
Multimodal prehabilitation
Frailty
Endometrial cancer
Lead sponsor: Charles University, Czech Republic
Sponsor class: OTHER
Collaborators: name: University Hospital Ostrava
name: University Hospital Olomouc
name: University Hospital Pilsen
name: The Faculty Hospital Na Bulovce
First posted: 2021-03-09
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Prehabilitation refers to interventions aiming to improve patients' resilience and functional capacity before a known stressful event, e.g., scheduled surgery. These interventions usually consist of physical activity and psychological and nutritional support. There is substantial evidence of the positive effect of multimodal prehabilitation among patients treated surgically for non-gynaecological cancers; however, no prospective data are available in gynaecological cancer patients.

PHOCUS trial is a prospective randomised trial aiming to evaluate the role of multimodal prehabilitation in patients with gynaecological cancer. Sixty-four patients will be randomised in single institution within 36 months with a 1:1 ratio into ARM A: control arm which will be provided with a basic information and standard of care support; ARM B: active arm undergoing multimodal prehabilitation composed of physical activity and psychological and nutritional support. All patients will be assessed at standard intervals (three times during the trial) by a spectrum of non-invasive tests, evaluating physical functional capacity, postoperative morbidity, nutritional status, level of stress and anxiety, and quality of life.

Detailed description: The objective of the trial is to evaluate the impact of intensive multimodal prehabilitation protocol on pre-operative functional capacity, postoperative morbidity, and quality of life in patients undergoing surgical treatment for gynaecological cancer.

Two groups of patients scheduled for postponed surgical treatment will be eligible for the trial: i) advanced ovarian cancer patients referred for neoadjuvant chemotherapy and interval debulking surgery; ii) stage I-II endometrial cancer patients classifying as frail (according to the validated modified Frailty Index), who will be treated by hormonal therapy for three months, followed by surgical treatment.

Eligibility criteria: Inclusion criteria

Two groups of patients will be eligible for the trial:

i) Epithelial ovarian cancer patients referred for NACT: a) FIGO stage III or IV disease; b) Patient is not a candidate for primary debulking surgery; c) Patient is a suitable candidate for standard of care combined chemotherapy; d) Patient is a candidate for interval.debulking surgery

ii) Stage I or II endometrial cancer patients classifying as frail according to the validated modified Frailty Index: a) FIGO stage I or II; b) Patient is classified as frail; c) Patient is suitable candidate for hormonal therapy.

Exclusion criteria

1. Second malignant tumour (under the treatment)
2. Patient is not suitable for any surgery delay
3. Patient is not physically able to meet the prehabilitation intervention plan or is unable to walk

Primary outcomes:
measure: Functional capacity changes
timeFrame: 9-12weeks
Secondary outcomes:
measure: Postoperative morbidity
timeFrame: 9-12weeks
measure: Length of postoperative hospital stay (days)
timeFrame: 9-12weeks
measure: Adherence to training program
timeFrame: 9-12weeks
measure: Effects of nutritional support program on body composition (weight of fat and lean body mass in kg)
timeFrame: 9-12weeks
measure: Effects of nutritional support program on resting energy expenditure (measured in kcal/kg).
timeFrame: 9-12weeks
measure: Effects of nutritional support program on Fatty acids composition of plasmatic and erythrocytes phospholipids (measured in mol%).
timeFrame: 9-12weeks
measure: Health-related quality of life
timeFrame: 9-12weeks
measure: Psychological health: DEPRESSION
timeFrame: 9-12weeks
measure: Psychological health: ANXIETY
timeFrame: 9-12weeks
measure: Psychological health: NONSPECIFIC PERCEIVED STRESS
timeFrame: 9-12weeks
measure: Psychological health: SPECIFIC PERCEIVED STRESS
timeFrame: 9-12weeks
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: Gynecologic Oncology Center in Prague
Study officials:
affiliation: Charles University, Czech Republic
name: David Cibula, prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cook PC, Leit ME. Issues in the pediatric athlete. Orthop Clin North Am. 1995 Jul;26(3):453-64.
citation: Althoff FC, Neb H, Herrmann E, Trentino KM, Vernich L, Fullenbach C, Freedman J, Waters JH, Farmer S, Leahy MF, Zacharowski K, Meybohm P, Choorapoikayil S. Multimodal Patient Blood Management Program Based on a Three-pillar Strategy: A Systematic Review and Meta-analysis. Ann Surg. 2019 May;269(5):794-804. doi: 10.1097/SLA.0000000000003095.
citation: Peteroy ET, Pirrello PE, Adams N. The relationship between two Wiggins Content Scales and length of hospitalization. J Clin Psychol. 1982 Apr;38(2):344-6. doi: 10.1002/1097-4679(198204)38:23.0.co;2-z.
citation: Barberan-Garcia A, Ubre M, Roca J, Lacy AM, Burgos F, Risco R, Momblan D, Balust J, Blanco I, Martinez-Palli G. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial. Ann Surg. 2018 Jan;267(1):50-56. doi: 10.1097/SLA.0000000000002293.
citation: Beck A, Vind Thaysen H, Hasselholt Soegaard C, Blaakaer J, Seibaek L. Prehabilitation in cancer care: patients' ability to prepare for major abdominal surgery. Scand J Caring Sci. 2021 Mar;35(1):143-155. doi: 10.1111/scs.12828. Epub 2020 Feb 11.
citation: Benzo R, Wigle D, Novotny P, Wetzstein M, Nichols F, Shen RK, Cassivi S, Deschamps C. Preoperative pulmonary rehabilitation before lung cancer resection: results from two randomized studies. Lung Cancer. 2011 Dec;74(3):441-5. doi: 10.1016/j.lungcan.2011.05.011. Epub 2011 Jun 12.
citation: Biglia N, Zanfagnin V, Daniele A, Robba E, Bounous VE. Lower Body Lymphedema in Patients with Gynecologic Cancer. Anticancer Res. 2017 Aug;37(8):4005-4015. doi: 10.21873/anticanres.11785.
citation: Blackwell JEM, Doleman B, Boereboom CL, Morton A, Williams S, Atherton P, Smith K, Williams JP, Phillips BE, Lund JN. High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial. Prostate Cancer Prostatic Dis. 2020 Dec;23(4):696-704. doi: 10.1038/s41391-020-0219-1. Epub 2020 Mar 10.
citation: Burden S, Todd C, Hill J, Lal S. Pre-operative nutrition support in patients undergoing gastrointestinal surgery. Cochrane Database Syst Rev. 2012 Nov 14;11:CD008879. doi: 10.1002/14651858.CD008879.pub2.
citation: Burke SM, Brunet J, Sabiston CM, Jack S, Grocott MP, West MA. Patients' perceptions of quality of life during active treatment for locally advanced rectal cancer: the importance of preoperative exercise. Support Care Cancer. 2013 Dec;21(12):3345-53. doi: 10.1007/s00520-013-1908-2. Epub 2013 Aug 3.
citation: Carli F, Brown R, Kennepohl S. Prehabilitation to enhance postoperative recovery for an octogenarian following robotic-assisted hysterectomy with endometrial cancer. Can J Anaesth. 2012 Aug;59(8):779-84. doi: 10.1007/s12630-012-9734-4. Epub 2012 May 26.
citation: Cianci S, Tarascio M, Rosati A, Caruso S, Uccella S, Cosentino F, Scaletta G, Gueli Alletti S, Scambia G. Sexual function and quality of life of patients affected by ovarian cancer. Minerva Med. 2019 Aug;110(4):320-329. doi: 10.23736/S0026-4806.19.06080-4. Epub 2019 May 6.
citation: Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8.
citation: Cortes-Guiral D, Mohamed F, Glehen O, Passot G. Prehabilitation of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Eur J Surg Oncol. 2021 Jan;47(1):60-64. doi: 10.1016/j.ejso.2020.01.032. Epub 2020 Jan 30.
citation: Daroszewski C, Stasiewicz M, Jazwinska-Tarnawska E, Rachwalik A, Mura E, Luboch-Kowal J, Drys A, Bogucki ZA, Brzecka A. Quality of Life in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Palliative Chemotherapy. Adv Exp Med Biol. 2019;1160:11-18. doi: 10.1007/5584_2019_346.
citation: Driver JA, Viswanathan AN. Frailty measure is more predictive of outcomes after curative therapy for endometrial cancer than traditional risk factors in women 60 and older. Gynecol Oncol. 2017 Jun;145(3):526-530. doi: 10.1016/j.ygyno.2017.03.010. Epub 2017 Mar 28.
citation: Ekici U, Ferhatoglu MF. Perioperative and Postoperative Effects of Preoperative Low-Calorie Restrictive Diets on Patients Undergoing Laparoscopic Sleeve Gastrectomy. J Gastrointest Surg. 2020 Feb;24(2):313-319. doi: 10.1007/s11605-019-04157-5. Epub 2019 Feb 20.
citation: Gillis C, Buhler K, Bresee L, Carli F, Gramlich L, Culos-Reed N, Sajobi TT, Fenton TR. Effects of Nutritional Prehabilitation, With and Without Exercise, on Outcomes of Patients Who Undergo Colorectal Surgery: A Systematic Review and Meta-analysis. Gastroenterology. 2018 Aug;155(2):391-410.e4. doi: 10.1053/j.gastro.2018.05.012. Epub 2018 May 8.
citation: Gillis C, Li C, Lee L, Awasthi R, Augustin B, Gamsa A, Liberman AS, Stein B, Charlebois P, Feldman LS, Carli F. Prehabilitation versus rehabilitation: a randomized control trial in patients undergoing colorectal resection for cancer. Anesthesiology. 2014 Nov;121(5):937-47. doi: 10.1097/ALN.0000000000000393.
citation: Goode PS. Efficacy of an assisted low-intensity programme of perioperative pelvic floor muscle training in improving the recovery of continence after radical prostatectomy: a randomized controlled trial. BJU Int. 2012 Oct;110(7):1010-1. doi: 10.1111/j.1464-410X.2012.11451.x. Epub 2012 Aug 22. No abstract available.
citation: Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012 May;125(2):477-82. doi: 10.1016/j.ygyno.2012.01.003. Epub 2012 Jan 11.
citation: Handforth C, Clegg A, Young C, Simpkins S, Seymour MT, Selby PJ, Young J. The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 2015 Jun;26(6):1091-1101. doi: 10.1093/annonc/mdu540. Epub 2014 Nov 17.
citation: Cho BC, Serini J, Zorrilla-Vaca A, Scott MJ, Gehrie EA, Frank SM, Grant MC. Impact of Preoperative Erythropoietin on Allogeneic Blood Transfusions in Surgical Patients: Results From a Systematic Review and Meta-analysis. Anesth Analg. 2019 May;128(5):981-992. doi: 10.1213/ANE.0000000000004005.
citation: Kei T, Mistry N, Curley G, Pavenski K, Shehata N, Tanzini RM, Gauthier MF, Thorpe K, Schweizer TA, Ward S, Mazer CD, Hare GMT. Efficacy and safety of erythropoietin and iron therapy to reduce red blood cell transfusion in surgical patients: a systematic review and meta-analysis. Can J Anaesth. 2019 Jun;66(6):716-731. doi: 10.1007/s12630-019-01351-6. Epub 2019 Mar 28.
citation: Li C, Carli F, Lee L, Charlebois P, Stein B, Liberman AS, Kaneva P, Augustin B, Wongyingsinn M, Gamsa A, Kim DJ, Vassiliou MC, Feldman LS. Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study. Surg Endosc. 2013 Apr;27(4):1072-82. doi: 10.1007/s00464-012-2560-5. Epub 2012 Oct 9.
citation: Li MH, Bolshinsky V, Ismail H, Burbury K, Ho KM, Amin B, Heriot A, Riedel B. A cross-sectional survey of Australian anesthetists' and surgeons' perceptions of preoperative risk stratification and prehabilitation. Can J Anaesth. 2019 Apr;66(4):388-405. doi: 10.1007/s12630-019-01297-9. Epub 2019 Jan 28.
citation: Marshall KM, Loeliger J, Nolte L, Kelaart A, Kiss NK. Prevalence of malnutrition and impact on clinical outcomes in cancer services: A comparison of two time points. Clin Nutr. 2019 Apr;38(2):644-651. doi: 10.1016/j.clnu.2018.04.007. Epub 2018 May 2.
citation: Mayo NE, Feldman L, Scott S, Zavorsky G, Kim DJ, Charlebois P, Stein B, Carli F. Impact of preoperative change in physical function on postoperative recovery: argument supporting prehabilitation for colorectal surgery. Surgery. 2011 Sep;150(3):505-14. doi: 10.1016/j.surg.2011.07.045.
citation: Mazzola M, Bertoglio C, Boniardi M, Magistro C, De Martini P, Carnevali P, Morini L, Ferrari G. Frailty in major oncologic surgery of upper gastrointestinal tract: How to improve postoperative outcomes. Eur J Surg Oncol. 2017 Aug;43(8):1566-1571. doi: 10.1016/j.ejso.2017.06.006. Epub 2017 Jun 23.
citation: McKenna NP, Bews KA, Al-Refaie WB, Colibaseanu DT, Pemberton JH, Cima RR, Habermann EB. Assessing Malnutrition Before Major Oncologic Surgery: One Size Does Not Fit All. J Am Coll Surg. 2020 Apr;230(4):451-460. doi: 10.1016/j.jamcollsurg.2019.12.034. Epub 2020 Feb 26.
citation: Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV, Ferri LE, Carli F. Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial. JAMA Surg. 2018 Dec 1;153(12):1081-1089. doi: 10.1001/jamasurg.2018.1645.
citation: Minnella EM, Bousquet-Dion G, Awasthi R, Scheede-Bergdahl C, Carli F. Multimodal prehabilitation improves functional capacity before and after colorectal surgery for cancer: a five-year research experience. Acta Oncol. 2017 Feb;56(2):295-300. doi: 10.1080/0284186X.2016.1268268. Epub 2017 Jan 12.
citation: Ohkura Y, Ichikura K, Shindoh J, Ueno M, Udagawa H, Matsushima E. Relationship between psychological distress and health-related quality of life at each point of the treatment of esophageal cancer. Esophagus. 2020 Jul;17(3):312-322. doi: 10.1007/s10388-019-00710-y. Epub 2020 Jan 2.
citation: Onstad MA, Schmandt RE, Lu KH. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment. J Clin Oncol. 2016 Dec 10;34(35):4225-4230. doi: 10.1200/JCO.2016.69.4638. Epub 2016 Nov 7.
citation: Pal N, Broaddus RR, Urbauer DL, Balakrishnan N, Milbourne A, Schmeler KM, Meyer LA, Soliman PT, Lu KH, Ramirez PT, Ramondetta L, Bodurka DC, Westin SN. Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device. Obstet Gynecol. 2018 Jan;131(1):109-116. doi: 10.1097/AOG.0000000000002390.
citation: Papadia A, Ragni N, Salom EM. The impact of obesity on surgery in gynecological oncology: a review. Int J Gynecol Cancer. 2006 Mar-Apr;16(2):944-52. doi: 10.1111/j.1525-1438.2006.00577.x.
citation: Rabischong B, Larrain D, Canis M, Le Bouedec G, Pomel C, Jardon K, Kwiatkowski F, Bourdel N, Achard JL, Dauplat J, Mage G. Long-term follow-up after laparoscopic management of endometrial cancer in the obese: a fifteen-year cohort study. J Minim Invasive Gynecol. 2011 Sep-Oct;18(5):589-96. doi: 10.1016/j.jmig.2011.05.015. Epub 2011 Jun 29.
citation: Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol. 2004 Oct;95(1):133-8. doi: 10.1016/j.ygyno.2004.06.045.
citation: Schier R, Levett D, Riedel B. Prehabilitation: The next challenge for anaesthesia teams. Eur J Anaesthesiol. 2020 Apr;37(4):259-262. doi: 10.1097/EJA.0000000000001167. No abstract available.
citation: Silver JK. Cancer prehabilitation and its role in improving health outcomes and reducing health care costs. Semin Oncol Nurs. 2015 Feb;31(1):13-30. doi: 10.1016/j.soncn.2014.11.003. Epub 2014 Dec 3.
citation: Wei J, Zhang W, Feng L, Gao W. Comparison of fertility-sparing treatments in patients with early endometrial cancer and atypical complex hyperplasia: A meta-analysis and systematic review. Medicine (Baltimore). 2017 Sep;96(37):e8034. doi: 10.1097/MD.0000000000008034.
citation: West MA, Loughney L, Lythgoe D, Barben CP, Sripadam R, Kemp GJ, Grocott MP, Jack S. Effect of prehabilitation on objectively measured physical fitness after neoadjuvant treatment in preoperative rectal cancer patients: a blinded interventional pilot study. Br J Anaesth. 2015 Feb;114(2):244-51. doi: 10.1093/bja/aeu318. Epub 2014 Oct 1.