Clinical trial NCT05233787: Trial Evaluating the Tailored Versus the Systematic Use of Defunctioning Stoma After Total Mesorectal Excision for Rectal Cancer (GRECCAR17)
Official title: A Phase III Randomized Trial Evaluating the Tailored Versus the Systematic Use of Defunctioning Stoma After Total Mesorectal Excision for Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Cancer
Ileostomy; Functional Disturbance
Keywords: Rectal Cancer
Defunctioning stoma
Quality of life
Pelvic sepsis
Functional outcomes
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2022-02-10
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quality of life over the 12 months after surgery
timeFrame: At 1, 4, 8, and 12 months of follow-up
Secondary outcomes:
measure: Proportion of anastomotic leakage
timeFrame: At 1 and 4 months after the rectal surgery
measure: The PF, RF, CF, EF, SF, FA, PA, NV, QL Dimensions of the QLQ-C30 questionnaire
timeFrame: At 1, 4, 8 and 12 months after the rectal surgery
measure: The urinary frequency
timeFrame: At 1, 4, 8, and 12 months post-surgery
measure: Blood or mucus in stools
timeFrame: At 1, 4, 8, and 12 months post-surgery
measure: Stool frequency
timeFrame: At 1, 4, 8, and 12 months post-surgery
measure: Body image dimensions of the QLQ-CR29 questionnaire
timeFrame: At 1, 4, 8, and 12 months post-surgery
measure: Rate of defunctioning stoma
timeFrame: At 1 month after the rectal surgery
measure: Low Anterior Resection Syndrome score (LARS score)
timeFrame: At 1, 4, 8 and 12 months after the rectal surgery
measure: Anal Incontinence (Wexner score)
timeFrame: At 1, 4, 8 and 12 months after the rectal surgery
measure: International Index of Erectile Function (IIEF)-5
timeFrame: At 1, 4, 8 and 12 months after the rectal surgery
measure: Female Sexual Function Index (FSFI) scale scores
timeFrame: At 1, 4, 8 and 12 months after the rectal surgery
measure: Urinary symptom profil (USP)
timeFrame: At 1, 4, 8, 12 months after the rectal surgery
measure: Postoperative morbidity (Clavien-Dindo score I-IV)
timeFrame: At 1 and 4 months after the rectal surgery
measure: Postoperative mortality (Clavien-Dindo score V)
timeFrame: At 1 and 4 months after the rectal surgery
measure: Proportion to work return after TME in active workers
timeFrame: Through study completion, an average of 1 year
measure: Time to work return after TME in active workers
timeFrame: Through study completion, an average of 1 year
measure: Quality of life over the 12 months after surgery
timeFrame: QLQ-C30 is assessed at 1, 4, 8 and 12 months after the rectal surgery
measure: Incremental cost-utility ratio defined as an incremental cost / Quality-Adjsuted Life Year (QALY) gained
timeFrame: From surgery to 12 months after surgery
measure: Total budgetary impact for French healthcare insurance system of spreading selective ostomy practice in France
timeFrame: From surgery to 12 months after surgery
measure: Indirect Costs (€) for French Healthcare insurance scheme of sickness leaves
timeFrame: From surgery to 12 months after surgery
measure: Changes in microbiome composition and diversity from baseline to 1 month
timeFrame: From baseline to Month 1
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens-Picardie - Service de Chirurgie Digestive
city: Besançon
country: France
facility: CHRU de Besançon - Service de Chirurgie Générale, Digestive et Cancérologique - Unité de Transplantation Hépatique
city: Bordeaux
country: France
facility: CHU de Bordeaux - Service de Chirurgie Digestive et Endocrinienne - Unité Colorectale
city: Bordeaux
country: France
facility: Clinique Tivoli Ducos - Service de Chirurgie Digestive
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand - Service de Chirurgie Digestive et Hépato-biliaire
city: Clichy
country: France
facility: APHP - Hôpital Beaujon - Service de Chirurgie Digestive
city: La Tronche
country: France
facility: CHU Grenoble Alpes - Service de Chirurgie Digestive
city: Le Kremlin-Bicêtre
country: France
facility: APHP - Hôpital Bicêtre - Service de Chirurgie Générale et Digestive
city: Lille
country: France
facility: CHU de Lille - Service de Chirurgie Générale et Digestive
city: Lyon
country: France
facility: Centre Lyonnais de Chirurgie Digestive
city: Marseille
country: France
facility: APHM - Hôpital La Timone - Service de Chirurgie Digestive et Générale
city: Marseille
country: France
facility: APHM - Hôpital Nord - Service de Chirurgie Digestive
city: Marseille
country: France
facility: Hôpital Européen de Marseille - Service de Chirurgie Digestive
city: Marseille
country: France
facility: Institut Paoli Calmette - Service de Chirurgie Digestive
city: Montpellier
country: France
facility: Institut du Cancer de Montpellier - Service de Chirurgie Digestive
city: Paris
country: France
facility: APHP - HEGP- Service de Chirurgie Digestive
city: Paris
country: France
facility: APHP - Hôpital Saint Antoine - Service de Chirurgie Digestive
city: Paris
country: France
facility: APHP - Hôpital Saint-Louis - Service de Chirurgie Viscérale, Cancérologique et Endocrinienne
city: Paris
country: France
facility: GH Diaconesses Croix Saint-Simon - Service de Chirurgie Digestive
city: Paris
country: France
facility: Groupe Hospitalier Paris St. Joseph - Service de Chirurgie Digestive et Obésité
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon - Sevice de Chirurgie Digestive
city: Rennes
country: France
facility: CHU de Rennes - Service de Chirurgie Hépatobiliaire et Digestive
city: Rouen
country: France
facility: CHU de Rouen - Service de Chirugie Digestive
city: Strasbourg
country: France
facility: CHRU de Strasbourg - Service de Chirurgie Générale et
city: Toulouse
country: France
facility: CHU de Toulouse - Service de Chirurgie Digestive
city: Tours
country: France
facility: CHRU de Tours - Service de Chirurgie Digestive Oncologique et Colorectale
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU de Nancy - Service de Chirugie Digestive, Hépatobiliaire, endocrinienne et Cancérologique
city: Villejuif
country: France
facility: Institut Gustave Roussy - Service de Chirurgie Viscérale Oncologique
Study officials:
affiliation: University Hospital, Bordeaux
name: Christophe LAURENT
role: PRINCIPAL_INVESTIGATOR
References: