Efficacy of Delayed Coloanal Anastomosis for Medium and Lower Rectum Cancer Treatment. Phase 2 Clinical Trial.
Phase: PHASE2
Conditions: Medium and Lower Rectal Cancer
Sponsor: Institut Bergonié

 
 
 
EFFICACY OF DELAYED COLOANAL ANASTOMOSIS FOR 
MEDIUM AND LOWER RECTUM CANCER TREATMENT. 
PHASE 2 CLINICAL TRIAL 
 
 
CASCADOR Protocol  
 
SYNOPSIS 
National multicentre trial 
 
Version No. 7 of 11/08/2016 – IB No.: IB 2010-08 
 
 
 
ClinicalTrials.gov Identifier: NCT01876901 
 
RCB ID No. 2010-A00299-30 
 
 
 
Coordinating Investigator 
Prof. Serge EVRARD 
Gastrointestinal Tumours Unit 
Gastrointestinal Surgical Oncologist 
Institut Bergonié 
 
229, cours de l’Argonne – 33076 BORDEAUX Cedex, France 
 
Tel.: +33 (0)556 333 261  – Fax: +33 (0)556 333 387 Email: s.evrard@bordeaux.unicancer.fr 
Clinical and Epidemiological Research Unit 
Prof. Simone MATHOULIN‐ PELISSIER  
Institut Bergonié, Bordeaux, France 
Head of the Clinical and Epidemiological Research Unit 
 
Carine BELLERA 
Institut Bergonié, Bordeaux, France 
Biostatistician 
 
Caroline LALET 
Institut Bergonié, Bordeaux, France 
Clinical Research Associate 
 
Barbara LORTAL, Emilie TOULZA                                                            Institut Bergonié, 
Bordeaux, France 
Pharmacists 
 
 
Economic analysis 
Dr Anne JAFFRE 
Institut Bergonié, Bordeaux, France 
Doctor, Department of Medical Information 
 
 
SPONSOR  
INSTITUT BERGONIÉ 

Institut Bergonié 
Synopsis/CASCADOR Protocol 
Version No. 7 of  11/08/2016 including material amendments 1-2-3-4-5-6            Page 2 of 4 
 
 
SYNOPSIS 
 
Title of study 
Efficacy of delayed coloanal anastomosis for medium and lower rectum 
cancer treatment. Phase II clinical trial.  
CASCADOR Protocol 
Acronym 
CASCADOR: ColoAnale Simple vs ColoAnale Différée en Oncologie Rectale 
(Simple Coloanal vs. Delayed Coloanal in Rectal Oncology) 
Sponsor 
Institut Bergonié  
Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest 
(Regional Cancer Centre of Bordeaux and the South-West) 
229, cours de l'Argonne 33076 Bordeaux Cedex FRANCE 
Coordinator 
Prof. Serge EVRARD, Gastrointestinal Tumours Unit 
Number of centres 
7 centres 
ACAD (delayed coloanal anastomosis) group: 3 centres 
- FCCC (French Comprehensive Cancer Centre) Institut Bergonié, Bordeaux, 
France 
- Hôpital de la Croix-Rousse, CHU (University Hospital Centre) Lyon, 
- CHU Grenoble, 
ACAI (immediate coloanal anastomosis) group: 4 centres 
- FCCC Léon-Bérard, Lyon, France, 
- Hôpital d’Adultes de Brabois, CHU Vandoeuvre-lès-Nancy, 
- Centre Alexis Vautrin, Vandœuvre-lès-Nancy, France 
- CHU Bordeaux 
 
Indications  
Medium and lower rectal cancer.  
Study design 
National multicentre phase II clinical trial 
Number of patients 
116 patients to be recruited (58 per group, see statistical analysis section).  
Study duration 
Enrollment begins: 2nd quarter 2010 
Enrollment ends: 30 April 2017 
Patient follow-up period: 2 years 
Study duration 9 years: 7 years of recruitment + 2 years of follow-up. 
Primary objective 
The aim of this study is to evaluate the efficacy of delayed coloanal anastomosis 
(ACAD) in the treatment of medium and lower rectal cancers at 30 days, in terms 
of symptomatic anastomotic fistula requiring a bypass stoma. 
Secondary 
objectives 
 Evaluation of the efficacy of immedite coloanal anastomosis (ACAI) in the 
treatment of medium and lower rectal cancers at 30 days, in terms of 
symptomatic anastomotic fistula requiring a bypass stoma. 
 According to the surgical technique used (ACAD or ACAI): 
o Evaluation of the number of patients with a stoma (at 30 days, 1 year, and 
2 years), 
o Evaluation of postoperative morbidity associated with coloanal anastomosis 
(at 30 days), 
o Evaluation of pre- and post-operative mortality (at 30 days), 
o Evaluation of progression-free survival (at 1 and 2 years), 
o Functional evaluation (quality of life, continence) (at 6 months, 1 year, and 
2 years), 
o Evaluation of the duration of hospitalisation and economic impact 
(immediate or deferred costs, at 30 days, 1 year, and 2 years). 
 Evaluation of the potential predictive role of the type of surgery on the 
occurrence of fistulas.  
Inclusion criteria 
1. Histologically proven rectal adenocarcinoma. 
2. Medium or lower rectum tumour requiring removal of the entire rectum and 
its mesorectum. 
3. T1 N+ or T2 N+ or T3 N+ or T3 N0 and M0 tumour. 
4. Aged between 18 and 75 years inclusive. 
5. ASA ≤ 2. 
6. Sphincter continence compatible with coloanal anastomosis. 

Institut Bergonié 
Synopsis/CASCADOR Protocol 
Version No. 7 of  11/08/2016 including material amendments 1-2-3-4-5-6            Page 3 of 4 
 
7. Patients who received preoperative radiotherapy alone or chemotherapy and 
radiotherapy. 
8. Patient registered with a social security system. 
9. For patients of childbearing age: use of contraception. 
10. 
Patient information and signed and dated informed consent. 
Exclusion criteria 
1. Other histology of rectal cancer. 
2. T1 N0 or T2 N0 or T4 tumour. 
3. Metastatic disease M1. 
4. History of cancer except cervical carcinoma in situ or basal cell carcinoma of 
the skin. 
5. Patients who for psychological, social, family or geographical reasons could 
not be treated or followed up regularly according to the study criteria; 
patients deprived of liberty or under guardianship. 
6. Pregnant or nursing women. 
Evaluation criteria 
Primary evaluation criteria  
The efficacy of each surgical procedure (ACAD and ACAI) will be evaluated in 
terms of patients with no symptomatic anastomotic fistula requiring a bypass 
stoma (ileostomy or colostomy, whether preventive or curative) for treatment in 
the first 30 days after surgery. 
An anastomotic fistula is defined by: 
 the escape of faeces through a drainage system, if one is present, or 
 a set of clinical signs (fever, subocclusion, etc.) requiring confirmation by 
pelvic scan (collection of fluid plus gas in the perianastomal area). 
 
Secondary evaluation criteria 
 The number of bypass stomas (preventive or therapeutic) will be evaluated. 
 Morbidity will be assessed in terms of grade 3 and 4 surgical complications 
according to the Dindo classification of surgical complications and the NCI-
CTCAE V3 toxicity scale. 
 Post-operative mortality will be assessed during the first 30 days after the 
date of surgery. 
 Progression-free survival will be assessed at 1 and 2 years. This is defined as 
the time between the date of the surgery and the date of the earliest of the 
following events: 
o The patient's death, whatever the cause, 
o Local or distant progression. 
 A functional assessment will be conducted in the month prior to surgery and 
at 6 months, 1 year, and 2 years after surgery: 
o Quality of life will be assessed using self-administered EORTC QLQ-C30 
questionnaire and its colorectal module QLQ-CR38. 
o Digestive functions, in particular anal incontinence, will be evaluated using 
the 5-item Jorge and Wexner scale.  
o An economic impact study will be conducted. Economic impact 
(hospitalisation, re-hospitalisation) will be evaluated using data from the 
French hospital discharge database (PMSI). The use of consumables during 
the operation and the fitting of temporary or permanent colostomy bags or 
ileostomy bags (loss of sphincter on fistula) until the eventual restoration of 
intestinal continuity will be evaluated. 
Description 
of 
treatments 
Whatever the mode of continuity restoration used, resection is the same in the 
two groups. It consists of total excision of the rectum and its mesorectum, 
whether the procedure is performed by laparotomy or laparoscopy. 
 ACAD group (Delayed Coloanal Anastomosis)  
After surgical resection, the colon is exteriorised through the anus and attached 
to the buttock with two stitches. 
On or around day 6, the exteriorised colon is resected and the coloanal 
anastomosis is performed without a preventive bypass stoma. 
 
 ACAI group (Immediate ColoAnal Anastomosis) 
After surgical resection, coloanal anastomosis is usually performed after creation 
of a J-pouch, when possible. In most cases, a preventive stoma is created. 

Institut Bergonié 
Synopsis/CASCADOR Protocol 
Version No. 7 of  11/08/2016 including material amendments 1-2-3-4-5-6            Page 4 of 4 
 
If there is no fistula, the patient will undergo another surgery for closure of the 
bypass stoma. 
Monitoring methods 
and duration 
A 30-day complications assessment will be done at the postoperative 
consultation (i.e. approximately 40-45 days after surgery, in practice). 
6 months after surgery, functional results will be assessed using quality of life 
questionnaires. 
Patients will be seen again at the 1- and 2-year postoperative marks to assess 
the functional outcome of their digestive system, using quality of life 
questionnaires. Their final recovery status will also be recorded.  
Patients will be monitored according to the usual follow-up of each surgeon.  
Study timeline 
 
 
Inclusion 
 
 
S 
U 
R 
G
E 
R 
Y 
40-45 days 
post-op 
6 months 
after 
surgery 
1 year 
after 
surgery 
2 years  
after 
surgery 
Inclusion/exclusio
n criteria 
 
X 
 
 
 
 
Informed consent 
signed 
X 
 
 
 
 
Pre-anaesthetic 
assessment 
X 
 
 
 
 
Quality 
of 
life 
questionnaires 
X 
 
X 
X 
X 
Assessment 
of 
complications 
 
X 
 
 
 
Functional 
digestive 
outcomes (stoma) 
 
 
X 
 
X 
 
X 
 
X 
Statistical analysis 
 
Determining the number of patients 
 ACAD group  
The primary judgement criterion was the efficacy of ACAD surgery as measured 
by the absence of fistula requiring a bypass stoma. We wish to demonstrate that 
the rate of patients with a fistula requiring a bypass stoma is less than 15%, i.e. 
the efficacy rate of ACAD is greater than 85%. Based on a one-sided binomial 
test with null and alternative hypotheses of 85% and 95% respectively, 53 
eligible and evaluable ACAD patients will be required (one-sided type I error of 
5% and power of 80%). If 49 or more patients (out of 53) have no fistula 
requiring a bypass stoma, then we will conclude that ACAD is effective. In order 
to anticipate possible non-evaluable patients, we plan to recruit 58 ACAD 
patients. 
 
 ACAI group  
 
In parallel, we plan to recruit 58 ACAI patients. 
Statistical analysis  
 Quantitative variables: number of values, number of missing data, mean, 
standard deviation, 95% confidence interval, median, 1st and 3rd quartiles, 
minimum and maximum.  
 Qualitative variables: number of values, number of missing data, frequency, 
percentage for each variable modality and exact confidence interval of each 
modality.  
 Survival data: Kaplan-Meier method, median survival times with 95% 
confidence interval, median follow-up (follow-up) using the reverse Kaplan-
Meier method, 
Benefits 
Putting forward a surgical technique associated with low morbidity for 
patients treated for medium and lower rectal cancer.