The Stoma Closure Before or After Adjuvant Therapy Trial

Rectal Cancer Clinical Trial

— STOMAD  

Official title:

Multicenter Randomized Controlled Phase III Trial Comparing Ileostomy Closure Before or After Adjuvant Therapy in Patients Operated for Rectal Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04372992
• Other study ID #: ROPCR01
• Status: Terminated
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: September 1, 2022

Study information

• Verified date: September 2022
• Source: Ospedale Umberto I di Torino
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label multicenter controlled trial, including 28 centers from the Rete Oncologica (Oncological Network) of Piemonte and Valle d'Aosta in Italy (http://www.reteoncologica.it). After a curative resection for rectal cancer and temporary ileostomy, 270 patients with indication to adjuvant chemotherapy will be randomized to early (before starting adjuvant treatment) or late (after adjuvant treatment completion) stoma closure. Primary end point will the compliance to adjuvant therapy. Secondary endpoint will include quality of life and bowel function evaluation, postoperative morbidity, chemotherapy toxicity, oncological outcomes and costs comparison.

Description:

Diverting ileostomy is effective in reducing severity of anastomotic complications in rectal low anterior resections and it is therefore widely used especially after neoadjuvant chemoradiation treatment. In current clinical practice, in patients with indication to adjuvant chemotherapy, closure of ileostomy is usually performed after the end of the treatment. However, a prolonged presence of the ostomy can induce the onset of ostomy-related complications such as stoma prolapse, parastomal hernia, mechanical ileus, high flow dehydration and damage to renal function. The ostomy-related complications may require unplanned or prolonged hospitalization, thus increasing costs. Furthermore, the presence of the stoma may affect quality of life, causing alteration of the body image and imposing changes in the daily routine and lifestyle. Early closure of the ileostomy in patients without signs of postoperative fistula has therefore been proposed. Outcomes of early closure (within one month from surgery) of diverting ileostomy were demonstrated to be equal to those of late closure (more than 12 weeks from surgery) in 2 randomized trials. Early closure may favor a better quality of life for patients, shortening the life-period with ileostomy, reduces health system economic expenditure and may represent the most desirable and convenient choice. It was also associated with better long term functional results in a randomized trial. In patients with indication to adjuvant therapy, however, timing to closure of the ostomy (before the start, during or at the end of treatment) is still a matter of debate in terms of compliance to systemic treatment, quality of life and overall costs. A recent multicenter retrospective study reported an increase in gastrointestinal toxicity in ostomy patients with a significant reduction in treatment compliance. On the other hand, early closure of the ostomy could unmask anterior resection syndrome (LARS) before chemotherapy, with potential negative impact on the tolerability of the treatment, or reveal postoperative complications thus delaying chemotherapy treatment. The trial will investigate which is the best strategy of dealing with temporary ileostomy in relation to adjuvant therapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: September 1, 2022
• Est. primary completion date: September 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient treated with a curative resection for rectal cancer
• Presence of a temporary ileostomy
• Age >= 18 years
• Indication to adjuvant treatment
• Absence of anastomotic dehiscence (as proved by enema and/or endoscopy)
• Able to give written informed consent

Exclusion Criteria:

• ASA >3
• ECOG Performance Status >=2
• UICC stage IV
• Severe and non-controlled systemic, oncologic, or infectious disease

Related Conditions & MeSH terms

• Ileostomy
• Rectal Cancer
• Rectal Neoplasms

Intervention

Other:
• Timing of stoma closure
Defining the best timing of stoma closure in relation to adjuvant therapy compliance

Locations

Country	Name	City	State
Italy	Ospedale Mons. Galliano - Chirurgia Generale (Dott. Serventi)	Acqui Terme	AL
Italy	Ospedale S. Lazzaro - Chirurgia Generale (Dott. Calgaro)	Alba
Italy	Ospedale SS. Antonio e Biagio - Chirurgia Generale (Dott. Priora)	Alessandria	AL
Italy	Ospedale Parini - Chirurgia Generale (Dott. Millo)	Aosta
Italy	Ospedale Cardinal Massaia - Chirurgia Generale (Dott. Sorisio)	Asti	AT
Italy	Ospedale degli Infermi - Chirurgia Generale (Dott. Polastri)	Biella	BI
Italy	IRCCS - Chirurgia Colorettale (Dott. Ribero)	Candiolo	TO
Italy	Ospedale S. Spirito - Chirurgia Generale (Dott. Amisano)	Casale Monferrato	AL
Italy	Ospedale di Ciriè - Chirurgia Generale (Dott. Personettaz)	Ciriè	TO
Italy	Ospedale S. Croce e Carle - Chirurgia Generale (Dott. Borghi)	Cuneo	CN
Italy	Ospedale S. Biagio - Chirurgia Generale (Dott. Zonta)	Domodossola	VB
Italy	Ospedale Civile - Chirurgia Generale (Dott. Rosato)	Ivrea	TO
Italy	Ospedale S. Croce - Chirurgia Generale (Dott. Cumbo)	Moncalieri	TO
Italy	Ospedale Regina Montis Regalis - Chirurgia Generale (Dott. Gattolin)	Mondovì	CN
Italy	Ospedale Maggiore della Carità - Chirurgia Generale (Dott. Romito)	Novara
Italy	Ospedale Maggiore della Carità - Chirurgia Universitaria (Prof. Gentilli)	Novara
Italy	Ospedale S. Giacomo - Chirurgia Generale (Dott. Di Somma)	Novi Ligure	AL
Italy	Ospedale S. Luigi - Chirurgia Universitaria (Prof. Degiuli)	Orbassano	TO
Italy	Ospedale Agnelli - Chirurgia Generale (Dott. Muratore)	Pinerolo	TO
Italy	Ospedale degli Infermi - Chirurgia Generale (Dott. Garino)	Rivoli	TO
Italy	Ospedale SS. Annunziata - Chirurgia Generale (Dott. Bertolino)	Savigliano	CN
Italy	Ospedale Cottolengo - Chirurgia Generale (Dott. Bima)	Torino	TO
Italy	Ospedale Humanitas Gradenigo - Chirurgia Generale (Dott. Leli)	Torino	TO
Italy	Ospedale Martini - Chirurgia Generale (Dott. Saracco)	Torino
Italy	Ospedale Mauriziano - Chirurgia Generale (Dott. Ferrero)	Torino
Italy	Ospedale Molinette - Chirurgia Generale (Dott. De Paolis)	Torino
Italy	Ospedale Molinette - Chirurgia Universitaria (Prof. Morino)	Torino
Italy	Ospedale S. Andrea - Chirurgia Generale (Dott. Testa)	Vercelli	VC

Sponsors (2)

Lead Sponsor	Collaborator
Ospedale Umberto I di Torino	Rete Oncologica Piemonte, Valle d'Aosta

Country where clinical trial is conducted

Italy, 

References & Publications (14)

Alves A, Panis Y, Lelong B, Dousset B, Benoist S, Vicaut E. Randomized clinical trial of early versus delayed temporary stoma closure after proctectomy. Br J Surg. 2008 Jun;95(6):693-8. doi: 10.1002/bjs.6212. — View Citation

Brown H, Randle J. Living with a stoma: a review of the literature. J Clin Nurs. 2005 Jan;14(1):74-81. Review. — View Citation

Chow A, Tilney HS, Paraskeva P, Jeyarajah S, Zacharakis E, Purkayastha S. The morbidity surrounding reversal of defunctioning ileostomies: a systematic review of 48 studies including 6,107 cases. Int J Colorectal Dis. 2009 Jun;24(6):711-23. doi: 10.1007/s00384-009-0660-z. Epub 2009 Feb 17. Review. — View Citation

Danielsen AK, Park J, Jansen JE, Bock D, Skullman S, Wedin A, Marinez AC, Haglind E, Angenete E, Rosenberg J. Early Closure of a Temporary Ileostomy in Patients With Rectal Cancer: A Multicenter Randomized Controlled Trial. Ann Surg. 2017 Feb;265(2):284-290. doi: 10.1097/SLA.0000000000001829. — View Citation

Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, Ledermann J, Sebag-Montefiore D. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014 Jul;25(7):1356-1362. doi: 10.1093/annonc/mdu147. Epub 2014 Apr 8. — View Citation

Herrle F, Sandra-Petrescu F, Weiss C, Post S, Runkel N, Kienle P. Quality of Life and Timing of Stoma Closure in Patients With Rectal Cancer Undergoing Low Anterior Resection With Diverting Stoma: A Multicenter Longitudinal Observational Study. Dis Colon Rectum. 2016 Apr;59(4):281-90. doi: 10.1097/DCR.0000000000000545. — View Citation

Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. doi: 10.1016/S1470-2045(12)70116-X. Epub 2012 Apr 13. — View Citation

Keane C, Park J, Öberg S, Wedin A, Bock D, O'Grady G, Bissett I, Rosenberg J, Angenete E. Functional outcomes from a randomized trial of early closure of temporary ileostomy after rectal excision for cancer. Br J Surg. 2019 Apr;106(5):645-652. doi: 10.1002/bjs.11092. Epub 2019 Feb 1. — View Citation

Malik T, Lee MJ, Harikrishnan AB. The incidence of stoma related morbidity - a systematic review of randomised controlled trials. Ann R Coll Surg Engl. 2018 Sep;100(7):501-508. doi: 10.1308/rcsann.2018.0126. Epub 2018 Aug 16. Review. — View Citation

Montedori A, Cirocchi R, Farinella E, Sciannameo F, Abraha I. Covering ileo- or colostomy in anterior resection for rectal carcinoma. Cochrane Database Syst Rev. 2010 May 12;(5):CD006878. doi: 10.1002/14651858.CD006878.pub2. Review. — View Citation

Park J, Angenete E, Bock D, Correa-Marinez A, Danielsen AK, Gehrman J, Haglind E, Jansen JE, Skullman S, Wedin A, Rosenberg J. Cost analysis in a randomized trial of early closure of a temporary ileostomy after rectal resection for cancer (EASY trial). Surg Endosc. 2020 Jan;34(1):69-76. doi: 10.1007/s00464-019-06732-y. Epub 2019 Mar 25. — View Citation

Robertson JP, Wells CI, Vather R, Bissett IP. Effect of Diversion Ileostomy on the Occurrence and Consequences of Chemotherapy-Induced Diarrhea. Dis Colon Rectum. 2016 Mar;59(3):194-200. doi: 10.1097/DCR.0000000000000531. — View Citation

Siassi M, Hohenberger W, Lösel F, Weiss M. Quality of life and patient's expectations after closure of a temporary stoma. Int J Colorectal Dis. 2008 Dec;23(12):1207-12. doi: 10.1007/s00384-008-0549-2. Epub 2008 Aug 7. — View Citation

Tulchinsky H, Shacham-Shmueli E, Klausner JM, Inbar M, Geva R. Should a loop ileostomy closure in rectal cancer patients be done during or after adjuvant chemotherapy? J Surg Oncol. 2014 Mar;109(3):266-9. doi: 10.1002/jso.23493. Epub 2013 Nov 19. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants with good compliance to adjuvant therapy	Composite outcome measure including timeliness and percentage of planned dose received.; In each subject, treatment compliance is defined as good if both the following conditions are met: adjuvant therapy starting date within 10 weeks of rectal resection; total cumulative received dose (mg/m2) >=70% of planned. The percentage of participants with good compliance in both arms will be compared.	Measured within 48 hours after the end of the last cycle of adjuvant therapy
Secondary	Rate of stoma-related complications	Adverse events related to the presence of stoma and postoperative complication after stoma closure	All over the study duration (up to 12 months from randomization)
Secondary	Rate of chemotherapy side effects	According to CTCAE classification	Immediately after the end of every single cycle (each cycle duration varies from 5 to 14 days according to the chosen scheme)
Secondary	Quality of life 1	Measured by EORTC C30	At baseline, at the end of cycle 3 (regardless of the cycle duration, that varies from 5 to 14 day according to local investigators choice) and at 12 months from randomization
Secondary	Quality of life 2	Measured by EORTC CR29	At baseline, at the end of cycle 3 (regardless of the cycle duration, that varies from 5 to 14 day according to local investigators choice) and at 12 months from randomization
Secondary	Quality of life 3	Measured by EQ-5D-3L	At baseline, at the end of cycle 3 (regardless of the cycle duration, that varies from 5 to 14 day according to local investigators choice) and at 12 months from randomization
Secondary	Bowel function	Measured by LARS (Low Anterior Resection Syndrome) score	At 12 months from rectal resection
Secondary	Overall survival	From randomization date to death from any cause or date of last contact	Ut to 3 years from inclusion of the last patient
Secondary	Progression free survival	From randomization date to progression diagnosis or date of last contact	Ut to 3 years from inclusion of the last patient
Secondary	Costs analysis	Mean cumulative costs in euro of the postoperative phase including outpatient visits, hospital stay for stoma closure, hospital re-entry and expenditures for stoma care appliances based on life-days with the stoma. Excluded are costs related to adjuvant treatment.	At 12 months from randomization