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

Rectal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05233787
• Other study ID #: CHUBX 2021/10
• Status: Recruiting
• Phase: N/A
• Start date: March 24, 2022
• Est. completion date: September 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Bordeaux
• Contact: Christophe LAURENT
• Phone: (0)5 57 65 67 69
• Email: christophe.laurent[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 212
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ileostomy; Functional Disturbance
• Rectal Cancer
• Rectal Neoplasms

Intervention

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)
• Systematic use of defunctioning stoma
Systematic use of defunctioning stoma for 2-3 months after TME, according to French national and international guidelines

Locations

Country	Name	City	State
France	CHU Amiens-Picardie - Service de Chirurgie Digestive	Amiens
France	CHRU de Besançon - Service de Chirurgie Générale, Digestive et Cancérologique - Unité de Transplantation Hépatique	Besançon
France	CHU de Bordeaux - Service de Chirurgie Digestive et Endocrinienne - Unité Colorectale	Bordeaux
France	Clinique Tivoli Ducos - Service de Chirurgie Digestive	Bordeaux
France	CHU de Clermont-Ferrand - Service de Chirurgie Digestive et Hépato-biliaire	Clermont-Ferrand
France	APHP - Hôpital Beaujon - Service de Chirurgie Digestive	Clichy
France	CHU Grenoble Alpes - Service de Chirurgie Digestive	La Tronche
France	APHP - Hôpital Bicêtre - Service de Chirurgie Générale et Digestive	Le Kremlin-Bicêtre
France	CHU de Lille - Service de Chirurgie Générale et Digestive	Lille
France	Centre Lyonnais de Chirurgie Digestive	Lyon
France	APHM - Hôpital La Timone - Service de Chirurgie Digestive et Générale	Marseille
France	APHM - Hôpital Nord - Service de Chirurgie Digestive	Marseille
France	Hôpital Européen de Marseille - Service de Chirurgie Digestive	Marseille
France	Institut Paoli Calmette - Service de Chirurgie Digestive	Marseille
France	Institut du Cancer de Montpellier - Service de Chirurgie Digestive	Montpellier
France	APHP - HEGP- Service de Chirurgie Digestive	Paris
France	APHP - Hôpital Saint Antoine - Service de Chirurgie Digestive	Paris
France	APHP - Hôpital Saint-Louis - Service de Chirurgie Viscérale, Cancérologique et Endocrinienne	Paris
France	GH Diaconesses Croix Saint-Simon - Service de Chirurgie Digestive	Paris
France	Groupe Hospitalier Paris St. Joseph - Service de Chirurgie Digestive et Obésité	Paris
France	Hospices Civils de Lyon - Sevice de Chirurgie Digestive	Pierre-Bénite
France	CHU de Rennes - Service de Chirurgie Hépatobiliaire et Digestive	Rennes
France	CHU de Rouen - Service de Chirugie Digestive	Rouen
France	CHRU de Strasbourg - Service de Chirurgie Générale et	Strasbourg
France	CHU de Toulouse - Service de Chirurgie Digestive	Toulouse
France	CHRU de Tours - Service de Chirurgie Digestive Oncologique et Colorectale	Tours
France	CHRU de Nancy - Service de Chirugie Digestive, Hépatobiliaire, endocrinienne et Cancérologique	Vandœuvre-lès-Nancy
France	Institut Gustave Roussy - Service de Chirurgie Viscérale Oncologique	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of life over the 12 months after surgery	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	Proportion of anastomotic leakage	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
Secondary	The PF, RF, CF, EF, SF, FA, PA, NV, QL Dimensions of the QLQ-C30 questionnaire	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
Secondary	The urinary frequency	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
Secondary	Blood or mucus in stools	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
Secondary	Stool frequency		At 1, 4, 8, and 12 months post-surgery
Secondary	Body image dimensions of the QLQ-CR29 questionnaire	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
Secondary	Rate of defunctioning stoma	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
Secondary	Low Anterior Resection Syndrome score (LARS score)	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
Secondary	Anal Incontinence (Wexner score)	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
Secondary	International Index of Erectile Function (IIEF)-5	Measured in male patients	At 1, 4, 8 and 12 months after the rectal surgery
Secondary	Female Sexual Function Index (FSFI) scale scores	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
Secondary	Urinary symptom profil (USP)	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
Secondary	Postoperative morbidity (Clavien-Dindo score I-IV)	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
Secondary	Postoperative mortality (Clavien-Dindo score V)	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
Secondary	Proportion to work return after TME in active workers	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
Secondary	Time to work return after TME in active workers	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
Secondary	Quality of life over the 12 months after 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
Secondary	Incremental cost-utility ratio defined as an incremental cost / Quality-Adjsuted Life Year (QALY) gained	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
Secondary	Total budgetary impact for French healthcare insurance system of spreading selective ostomy practice in France	5-year financial model	From surgery to 12 months after surgery
Secondary	Indirect Costs (€) for French Healthcare insurance scheme of sickness leaves	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
Secondary	Changes in microbiome composition and diversity from baseline to 1 month	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