The Stoma Closure Before or After Adjuvant Therapy Trial

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Ileostomy, Rectal Cancer

Intervention / Treatment
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* Other: Timing of stoma closure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early stoma closure<br>Ileostomy closure between 30 and 40 day after rectal resection | Other: Timing of stoma closure<br>* Defining the best timing of stoma closure in relation to adjuvant therapy compliance<br>|
| Active Comparator: Delayed stoma closure<br>Ileostomy closure 15 days from the end of adjuvant therapy (up to 60 days) | Other: Timing of stoma closure<br>* Defining the best timing of stoma closure in relation to adjuvant therapy compliance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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) | 
| 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 | 
| 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 | 
| 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 | 
| Bowel function | Measured by LARS (Low Anterior Resection Syndrome) score | At 12 months from rectal resection | 
| 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 | 
| Progression free survival | From randomization date to progression diagnosis or date of last contact | Ut to 3 years from inclusion of the last patient | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early closure, Chemotherapy, Adjuvant, Late closure