Trial Evaluating the Tailored Versus the Systematic Use of Defunctioning Stoma After Total Mesorectal Excision for Rectal Cancer (GRECCAR17) (GRECCAR17)

May 14, 2024 updated by: University Hospital, Bordeaux

A Phase III Randomized Trial Evaluating the Tailored Versus the Systematic Use of Defunctioning Stoma After Total Mesorectal Excision for Rectal Cancer

GRECCAR 17 will be the first prospective and randomized trial to assess a tailored policy in the use of defunctioning stoma after TME according to the personalized risk of anastomotic leakage. The tailored use of defunctioning stoma after TME for rectal cancer should improve both the quality of life of patients and the anorectal function, without any impact on anastomotic leakage. Moreover, for the healthcare system, this new approach could be a cost-effective strategy, leading to a decrease in healthcare expenses.

The main objective is to compare the impact of tailored defunctioning stoma after TME for rectal cancer versus the systematic use of defunctioning stoma on the evolution of the specific Quality Of Life (QLQC30) during the 12 months after surgery.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The introduction of Total Mesorectal Excision (TME) as the surgical procedure of choice for low and mid rectal cancer has led to decrease local recurrence and improved oncological results. Postoperative morbidity remains a major issue, and the most feared complication is anastomotic leakage. The systematic use of a defunctioning stoma during 3 months to protect low colorectal anastomosis (below than 7 cm from the anal verge) is the standard of practice after TME surgery in order to decrease risks of anastomotic leakage and urgent re-operations.

However, there have been a lot of controversies surrounding the role of defunctioning stoma mainly due to stoma-related complications, ranked from 20% to 60%, which may lead to prolonged inpatient care, urgent re-operation and devastating effects on quality of life (QOL) and healthcare expenses. Moreover, it has been reported that patients either without defunctioning stoma, or with early stoma closure (days 8-12 after TME) have a better functional outcomes than patients with systematic defunctioning stoma for 3 months.

The experimental arm (arm A) will benefit from a tailored use of defunctioning stoma after TME based on a 2-step process: i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leakage (defunctioning stoma only if Anastomotic Failure Observed Risk Score=[2-6]), ii) to perform an early stoma closure at day 8-12, according to clinical (fever), biological (CRP level days 2 and 4 postoperatively) and radiological postoperative assessment (CT-scan with colonic contrast retrograde enema day 7-8 postoperatively). The control arm (arm B) will benefit from systematic use of defunctioning stoma for 2-3 months after TME, according to French national and international guidelines.

Patients will be followed at 1, 4, 8 and 12 months after surgery, with chest, abdominal and pelvic scan and tumour markers.

Study Type

Interventional

Enrollment (Estimated)

212

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France
      • Besançon, France
        • Not yet recruiting
        • CHRU de Besançon - Service de Chirurgie Générale, Digestive et Cancérologique - Unité de Transplantation Hépatique
        • Contact:
      • Bordeaux, France
      • Bordeaux, France
      • Clermont-Ferrand, France
        • Not yet recruiting
        • CHU de Clermont-Ferrand - Service de Chirurgie Digestive et Hépato-biliaire
        • Contact:
      • Clichy, France
        • Not yet recruiting
        • APHP - Hôpital Beaujon - Service de Chirurgie Digestive
        • Contact:
      • La Tronche, France
      • Le Kremlin-Bicêtre, France
        • Recruiting
        • APHP - Hôpital Bicêtre - Service de Chirurgie Générale et Digestive
        • Contact:
      • Lille, France
      • Lyon, France
      • Marseille, France
      • Marseille, France
      • Marseille, France
        • Recruiting
        • APHM - Hôpital La Timone - Service de Chirurgie Digestive et Générale
        • Contact:
      • Marseille, France
        • Recruiting
        • APHM - Hôpital Nord - Service de Chirurgie Digestive
        • Contact:
      • Montpellier, France
      • Paris, France
        • Not yet recruiting
        • APHP - Hôpital Saint-Louis - Service de Chirurgie Viscérale, Cancérologique et Endocrinienne
        • Contact:
      • Paris, France
        • Not yet recruiting
        • Groupe Hospitalier Paris St. Joseph - Service de Chirurgie Digestive et Obésité
        • Contact:
      • Paris, France
        • Recruiting
        • APHP - HEGP- Service de Chirurgie Digestive
        • Contact:
      • Paris, France
        • Recruiting
        • APHP - Hôpital Saint Antoine - Service de Chirurgie Digestive
        • Contact:
      • Paris, France
        • Recruiting
        • GH Diaconesses Croix Saint-Simon - Service de Chirurgie Digestive
        • Contact:
      • Pierre-Bénite, France
        • Recruiting
        • Hospices Civils de Lyon - Sevice de Chirurgie Digestive
        • Contact:
      • Rennes, France
      • Rouen, France
      • Strasbourg, France
      • Toulouse, France
        • Not yet recruiting
        • CHU de Toulouse - Service de Chirurgie Digestive
        • Contact:
      • Tours, France
        • Recruiting
        • CHRU de Tours - Service de Chirurgie Digestive Oncologique et Colorectale
        • Contact:
      • Vandœuvre-lès-Nancy, France
        • Recruiting
        • CHRU de Nancy - Service de Chirugie Digestive, Hépatobiliaire, endocrinienne et Cancérologique
        • Contact:
      • Villejuif, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18-80 years;
  • Rectal adenocarcinoma (histologically proven)
  • No metastasis or medical history of colorectal metastasis (M0)
  • Patients with rectal cancer < 12 cm from the anal verge (determined by rectal examination or MRI)
  • Patients operated on by mini-invasive TME (laparoscopic, robotic or TaTME);
  • With or without neo adjuvant treatment
  • Realize a stapling anastomosis < 7 cm from the anal verge (determined by rectal examination or MRI)
  • Patients with expected defunctioning ileostomy
  • Appropriate hematologic function: hemoglobin ≥ 10.5 g/dL, leukocytes > 4000/mm3, blood platelets > 100,000/mm3);
  • Appropriate renal function (serum creatinine < 15 mg/dL);
  • Effective contraception of childbearing age : Male patients and premenopausal women should agree to use two medically validated contraceptive methods (one for the patient et one for the partner) during the study
  • Patient affiliated or beneficiary to a health security system;
  • Patient and doctor have signed informed consent

Exclusion Criteria:

  • Patients with rectal cancer requiring TME surgery with handsewn anastomosis;
  • Patients operated on by open approach;
  • Previous pelvic irradiation for reasons other than rectal cancer
  • Concomitant cancer or medical history of cancer within 5 years other than cancers treated in situ (cervical carcinoma or basocellular carcinoma or spinocellular carcinoma)
  • Patients with expected defunctioning colostomy;
  • Patients with perforated rectal cancer or preoperative pelvic sepsis;
  • Patients with inflammatory bowel disease and/or bowel obstruction,
  • Patients operated on in emergency;
  • Patients with poor nutrition (Albumin < 34 g/L, pre-Alb < 0.14 g/L)
  • Patients with extended-TME or pelvic exenteration (prostate);
  • Patients with history of heart or vascular ischemia;
  • Severe heart disease or congestive heart disease;
  • Patients with immunodeficiency and/or under corticotherapy;
  • Severe lung disease or respiratory failure;
  • Severe kidney disease;
  • Previous disease or disability expected to influence the assessment of postoperative QOL;
  • Pregnancy or breast feeding;
  • Persons deprived of liberty or under guardianship (curatorship or tutorship) or incapable of giving consent;
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol or follow-up scheduled.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Tailored use of defunctioning stoma after TME

The tailored use of defunctioning stoma includes two steps:

  • Firstly, the decision to use or not a defunctioning stoma will be based on the personalized risk of anastomotic leakage (according to AFOR score). This score is ranked from 0 to 6, and includes gender, Body Mass Index, smoking, diabetes, tumor size and preoperative radiotherapy.
  • Patients with AFORS equal to 0 or 1 (risk of anastomotic leakage less than 10%) will not have defunctioning stoma;
  • Patients with AFORS equal to or between 2 and 6 (risk of anastomotic leakage more than 20%) will have a defunctioning stoma.
  • Secondly, in patients with a defunctioning stoma, an early closure will be performed day 8-12 after TME if:
  • No fever postoperatively (≤ 38°C),
  • CRP at day 2 lower than 115mg/L (+/- 10 mg/L), decreasing at day 4,
  • CT-scan with colonic contrast retrograde enema showing no anastomotic leakage.
Procedure: Tailored use of defunctioning stoma after TME

Tailored use of defunctioning stoma after TME based on a 2-step process:

i) to perform or not a defunctioning stoma according to the personalized risk of anastomotic leakage (defunctioning stoma only if Anastomotic Failure Observed Risk Score=[2-6]), ii) to perform an early stoma closure at day 8-12, according to clinical (fever), biological (CRP level days 2 and 4 postoperatively) and radiological postoperative assessment (CT-scan with colonic contrast retrograde enema day 7-8 postoperatively)
Active Comparator: Arm B: Systematic use of defunctioning stoma
Systematic use of defunctioning stoma for 3 months after TME according to French national guidelines
Procedure: Systematic use of defunctioning stoma
Systematic use of defunctioning stoma for 2-3 months after TME, according to French national and international guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quality of life over the 12 months after surgery
Time Frame: At 1, 4, 8, and 12 months of follow-up

The QLQ-C30 is a patient self-rating questionnaire (30 questions) that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. Scores can be linearly transformed to provide a score from 0 to 100 REF. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.

The area under the quality of life curve will be measured over the 12 months after rectal surgery, with measurement time points at 1, 4, 8 and 12 months.
At 1, 4, 8, and 12 months of follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of anastomotic leakage
Time Frame: At 1 and 4 months after the rectal surgery
Proportion of patients with an anastomotic leakage will be assessed by a clinical exam (with a rectal examination) at 1 month and with a clinical exam (with a rectal examination) and a CT scan at 4 months after rectal surgery
At 1 and 4 months after the rectal surgery
The PF, RF, CF, EF, SF, FA, PA, NV, QL Dimensions of the QLQ-C30 questionnaire
Time Frame: At 1, 4, 8 and 12 months after the rectal surgery

  1. 9 dimensions will be assessed with:

    • PF : Physical Functioning
    • RF : Role Functioning
    • CF : Cognitive Functioning
    • EF : Emotional Functioning
    • SF: Social Functioning
    • FA : Fatigue
    • PA : Pain
    • NV : Nausea and Vomiting

    • QL : Global health status

      2- The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. This is a patients self-rating questionnaire that measures five functional scales (physical, role, social, emotional, and cognitive) three symptom scales (fatigue, pain, nausea and vomiting) A global health status / QoL scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease. Scores can be linearly transformed to provide a score from 0 to 100 REF. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
At 1, 4, 8 and 12 months after the rectal surgery
The urinary frequency
Time Frame: At 1, 4, 8, and 12 months post-surgery

The QLQ-CR29 (Quality of life of rectal cancer patients with 29 questions) has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items.

Urinary frequency is measured with items 1 and 2 of the questionnaire. The score can range from 0 to 100.

Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
At 1, 4, 8, and 12 months post-surgery
Blood or mucus in stools
Time Frame: At 1, 4, 8, and 12 months post-surgery

The QLQ-CR29 (Quality of life of rectal cancer patients with 29 questions) has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items.

The blood or mucus in stools is measured with items 8 and 9 of the questionnaire. The score can range from 0 to 50.

Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
At 1, 4, 8, and 12 months post-surgery
Stool frequency
Time Frame: At 1, 4, 8, and 12 months post-surgery
At 1, 4, 8, and 12 months post-surgery
Body image dimensions of the QLQ-CR29 questionnaire
Time Frame: At 1, 4, 8, and 12 months post-surgery
The QLQ-CR29 (Quality of life of rectal cancer patients with 29 questions) has five functional and 18 symptom scales. Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
At 1, 4, 8, and 12 months post-surgery
Rate of defunctioning stoma
Time Frame: At 1 month after the rectal surgery
Proportion of patients who have a defunctioning stoma. It will be assessed at the time of the consultation at 1 month with the collection of the adverse events (AE) and the serious adverse events (SAE)
At 1 month after the rectal surgery
Low Anterior Resection Syndrome score (LARS score)
Time Frame: At 1, 4, 8 and 12 months after the rectal surgery
The LARS questionnaire (low anterior resection score) evaluates bowel function. Five questions regarding incontinence for flatus and liquid stools, frequency, clustering and urgency for defecation are taken into account. The score ranges from 0 to 42 is divides into no LARS (0 to 20 points), minor LARS (21 to 29 points), and major LARS (30 to 42 points).
At 1, 4, 8 and 12 months after the rectal surgery
Anal Incontinence (Wexner score)
Time Frame: At 1, 4, 8 and 12 months after the rectal surgery
The WEXNER score assesses the importance of anal incontinence, it varies from 0 to 20, 20 corresponding to total anal incontinence
At 1, 4, 8 and 12 months after the rectal surgery
International Index of Erectile Function (IIEF)-5
Time Frame: At 1, 4, 8 and 12 months after the rectal surgery
Measured in male patients
At 1, 4, 8 and 12 months after the rectal surgery
Female Sexual Function Index (FSFI) scale scores
Time Frame: At 1, 4, 8 and 12 months after the rectal surgery
Measured in female patients. The Female Sexual Function Index (FSFI) is a 19-item self-report inventory designed to assess female sexual function. It comprises six domains: desire, arousal ,lubrication orgasm, satisfaction, pain. The maximum score for each domain is 6.0, obtained by summing item responses and multiplying by a correction factor. The total composite sexual function score is a sum of domain scores and ranges from 2.0 (not sexually active and no desire) to 36.0.
At 1, 4, 8 and 12 months after the rectal surgery
Urinary symptom profil (USP)
Time Frame: At 1, 4, 8, 12 months after the rectal surgery

The Urinary symptom profil (USP) assesses urinary symptoms among men and women with stress, urge (from 0 to 9), overactive bladder (from 0 to 9), or urinary obstructive symptoms (from 0 to 9).

The maximum corresponding to a bad result.
At 1, 4, 8, 12 months after the rectal surgery
Postoperative morbidity (Clavien-Dindo score I-IV)
Time Frame: At 1 and 4 months after the rectal surgery

This is a classification in order to rank a complication (surgical or medical morbidity) in an objective and reproducible manner.

It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The introduction of the subclasses a and b allows a contraction of the classification into 5 grades (I, II, III, IV and V) depending on the size of the population observed or the of the focus of a study.

It varies from 1 to 5, 5 corresponding to the death at the patient.
At 1 and 4 months after the rectal surgery
Postoperative mortality (Clavien-Dindo score V)
Time Frame: At 1 and 4 months after the rectal surgery

This is a classification in order to rank a complication (surgical or medical morbidity) in an objective and reproducible manner.

It consists of 7 grades (I, II, IIIa, IIIb, IVa, IVb and V). The introduction of the subclasses a and b allows a contraction of the classification into 5 grades (I, II, III, IV and V) depending on the size of the population observed or the of the focus of a study.

It varies from 1 to 5, 5 corresponding to the death at the patient.
At 1 and 4 months after the rectal surgery
Proportion to work return after TME in active workers
Time Frame: Through study completion, an average of 1 year
This endpoint is referring to the capability of active patients to resume their professional activity after surgery. In order to better describe this endpoint the investigators want to measure together the proportion of patients resuming their activity, and the time until resumption of professional activity.
Through study completion, an average of 1 year
Time to work return after TME in active workers
Time Frame: Through study completion, an average of 1 year
This endpoint is referring to the capability of active patients to resume their professional activity after surgery. In order to better describe this endpoint the investigators want to measure together the proportion of patients resuming their activity, and the time until resumption of professional activity.
Through study completion, an average of 1 year
Quality of life over the 12 months after surgery
Time Frame: QLQ-C30 is assessed at 1, 4, 8 and 12 months after the rectal surgery
The Quality of life of cancer contains 30 questions (QLQ-C30). This is a patients self-rating questionnaire that measures physical, role, social, emotional, and cognitive functions as well as overall QoL. Scores can be linearly transformed to provide a score from 0 to 100.Higher scores represent better functioning on the functional scales and a higher level of symptoms of the symptom scales.
QLQ-C30 is assessed at 1, 4, 8 and 12 months after the rectal surgery
Incremental cost-utility ratio defined as an incremental cost / Quality-Adjsuted Life Year (QALY) gained
Time Frame: From surgery to 12 months after surgery
Costs will be measured through the French Health Data Hub database. QALYs will be measured using the and EQ-5D-5L questionnaire.
From surgery to 12 months after surgery
Total budgetary impact for French healthcare insurance system of spreading selective ostomy practice in France
Time Frame: From surgery to 12 months after surgery
5-year financial model
From surgery to 12 months after surgery
Indirect Costs (€) for French Healthcare insurance scheme of sickness leaves
Time Frame: From surgery to 12 months after surgery
Measured through SNDS database (Système National des Données de Santé) and data from our study on sickness leaves and times to return to work
From surgery to 12 months after surgery
Changes in microbiome composition and diversity from baseline to 1 month
Time Frame: From baseline to Month 1
Data will be rarefied using the samples with the smallest number of reads and then subjected to alpha-diversity analysis employing Faith's phylogenetic diversity. Kruskal-Wallis will be calculated between all groups together and for pairwise comparisons. To find significant differences at the genera taxonomy level, ANCOM tests will be used to identify features that are differentially abundant across sample groups.
From baseline to Month 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Christophe LAURENT, University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2022

Primary Completion (Estimated)

September 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

November 8, 2021

First Submitted That Met QC Criteria

February 9, 2022

First Posted (Actual)

February 10, 2022

Study Record Updates

Last Update Posted (Actual)

May 16, 2024

Last Update Submitted That Met QC Criteria

May 14, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2021/10

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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