Clinical trial NCT04372992: The Stoma Closure Before or After Adjuvant Therapy Trial
Official title: Multicenter Randomized Controlled Phase III Trial Comparing Ileostomy Closure Before or After Adjuvant Therapy in Patients Operated for Rectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Ileostomy
Rectal Cancer
Keywords: Chemotherapy, Adjuvant
Early closure
Late closure
Lead sponsor: Ospedale Umberto I di Torino
Sponsor class: OTHER
Collaborators: name: Rete Oncologica Piemonte, Valle d'Aosta
First posted: 2020-05-04
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter controlled trial
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants with good compliance to adjuvant therapy
timeFrame: Measured within 48 hours after the end of the last cycle of adjuvant therapy
Secondary outcomes:
measure: Rate of stoma-related complications
timeFrame: All over the study duration (up to 12 months from randomization)
measure: Rate of chemotherapy side effects
timeFrame: Immediately after the end of every single cycle (each cycle duration varies from 5 to 14 days according to the chosen scheme)
measure: Quality of life 1
timeFrame: 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
measure: Quality of life 2
timeFrame: 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
measure: Quality of life 3
timeFrame: 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
measure: Bowel function
timeFrame: At 12 months from rectal resection
measure: Overall survival
timeFrame: Ut to 3 years from inclusion of the last patient
measure: Progression free survival
timeFrame: Ut to 3 years from inclusion of the last patient
measure: Costs analysis
timeFrame: At 12 months from randomization
Other outcomes:
Locations:
city: Acqui Terme
country: Italy
facility: Ospedale Mons. Galliano - Chirurgia Generale (Dott. Serventi)
state: AL
city: Alessandria
country: Italy
facility: Ospedale SS. Antonio e Biagio - Chirurgia Generale (Dott. Priora)
state: AL
city: Casale Monferrato
country: Italy
facility: Ospedale S. Spirito - Chirurgia Generale (Dott. Amisano)
state: AL
city: Novi Ligure
country: Italy
facility: Ospedale S. Giacomo - Chirurgia Generale (Dott. Di Somma)
state: AL
city: Asti
country: Italy
facility: Ospedale Cardinal Massaia - Chirurgia Generale (Dott. Sorisio)
state: AT
city: Biella
country: Italy
facility: Ospedale degli Infermi - Chirurgia Generale (Dott. Polastri)
state: BI
city: Cuneo
country: Italy
facility: Ospedale S. Croce e Carle - Chirurgia Generale (Dott. Borghi)
state: CN
city: Mondovì
country: Italy
facility: Ospedale Regina Montis Regalis - Chirurgia Generale (Dott. Gattolin)
state: CN
city: Savigliano
country: Italy
facility: Ospedale SS. Annunziata - Chirurgia Generale (Dott. Bertolino)
state: CN
city: Candiolo
country: Italy
facility: IRCCS - Chirurgia Colorettale (Dott. Ribero)
state: TO
city: Ciriè
country: Italy
facility: Ospedale di Ciriè - Chirurgia Generale (Dott. Personettaz)
state: TO
city: Ivrea
country: Italy
facility: Ospedale Civile - Chirurgia Generale (Dott. Rosato)
state: TO
city: Moncalieri
country: Italy
facility: Ospedale S. Croce - Chirurgia Generale (Dott. Cumbo)
state: TO
city: Orbassano
country: Italy
facility: Ospedale S. Luigi - Chirurgia Universitaria (Prof. Degiuli)
state: TO
city: Pinerolo
country: Italy
facility: Ospedale Agnelli - Chirurgia Generale (Dott. Muratore)
state: TO
city: Rivoli
country: Italy
facility: Ospedale degli Infermi - Chirurgia Generale (Dott. Garino)
state: TO
city: Torino
country: Italy
facility: Ospedale Cottolengo - Chirurgia Generale (Dott. Bima)
state: TO
city: Torino
country: Italy
facility: Ospedale Humanitas Gradenigo - Chirurgia Generale (Dott. Leli)
state: TO
city: Domodossola
country: Italy
facility: Ospedale S. Biagio - Chirurgia Generale (Dott. Zonta)
state: VB
city: Vercelli
country: Italy
facility: Ospedale S. Andrea - Chirurgia Generale (Dott. Testa)
state: VC
city: Alba
country: Italy
facility: Ospedale S. Lazzaro - Chirurgia Generale (Dott. Calgaro)
city: Aosta
country: Italy
facility: Ospedale Parini - Chirurgia Generale (Dott. Millo)
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità - Chirurgia Generale (Dott. Romito)
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità - Chirurgia Universitaria (Prof. Gentilli)
city: Torino
country: Italy
facility: Ospedale Martini - Chirurgia Generale (Dott. Saracco)
city: Torino
country: Italy
facility: Ospedale Mauriziano - Chirurgia Generale (Dott. Ferrero)
city: Torino
country: Italy
facility: Ospedale Molinette - Chirurgia Generale (Dott. De Paolis)
city: Torino
country: Italy
facility: Ospedale Molinette - Chirurgia Universitaria (Prof. Morino)
Study officials:
affiliation: OA Ordine Mauriziano - Torino, Italy
name: Paolo Massucco, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Massucco P, Fontana A, Mineccia M, Perotti S, Ciccone G, Galassi C, Giuffrida MC, Marino D, Monsellato I, Paris MK, Perinotti R, Racca P, Monagheddu C, Saccona F, Ponte E, Mistrangelo M, Santarelli M, Tomaselli F, Reddavid R, Birolo S, Calabro M, Pipitone N, Panier Suffat L, Carrera M, Potente F, Brunetti M, Rimonda R, Adamo V, Piscioneri D, Cravero F, Serventi A, Giaminardi E, Mazza L, Bellora P, Colli F, De Rosa C, Battafarano F, Trapani R, Mellano A, Gibin E, Bellomo P. Prospective, randomised, multicentre, open-label trial, designed to evaluate the best timing of closure of the temporary ileostomy (early versus late) in patients who underwent rectal cancer resection and with indication for adjuvant chemotherapy: the STOMAD (STOMa closure before or after ADjuvant therapy) randomised controlled trial. BMJ Open. 2021 Feb 19;11(2):e044692. doi: 10.1136/bmjopen-2020-044692.