Transanal Versus Laparoscopic Total Mesorectal Excision For Rectal Cancer

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT02966483

Collaborator

Peking Union Medical College Hospital (Other), The First Hospital of Jilin University (Other), RenJi Hospital (Other), Shengjing Hospital (Other), The Second People's Hospital of Yibin (Other), Daping Hospital and the Research Institute of Surgery of the Third Military Medical University (Other), Nanchong Central Hospital (Other), Zunyi Medical College (Other), The First Affiliated Hospital of University of South China (Other), Xinqiao Hospital (Other), Nanfang Hospital of Southern Medical University (Other), First Affiliated Hospital Xi'an Jiaotong University (Other), Ruijin Hospital (Other), The Affiliated Hospital of Guangdong Medical College (Other), The Third Xiangya Hospital of Central South University (Other)

1,114

Enrollment

Locations

Arms

111

Anticipated Duration (Months)

69.6

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Laparoscopic surgery for rectal cancer has been successfully proven to be a non-inferior alternative regarding resection quality, and oncological outcomes of patients as compared to open surgery in mangy clinical trails. Moreover, laparoscopic surgery is advantageous over open surgery with regard to operative invasiveness, patient's recovery, and wound related complications. Thus, laparoscopic surgery has gained great popularity over the past decades. However, specifically for mid and low rectal cancer, laparoscopic surgery is technically demanding, which sometimes leads to high morbidity and unsatisfactory resection quality, especially in challenging cases such as bulky mesorectum, enlarged prostate, irradiated pelvis, etc. Under this circumstance, transanal total mesorectal excision (TaTME) , the so called "down-to-up" alternative, has emerged as a promising solution to these problems in recent years and more and more small studies have proven the feasibility and advantages of this technique, making it become a hot topic among both literature and conferences. However, TaTME is still at early birth, higher-level evidences, either multicentric, or comparative study with conventional surgery is strikingly lacking. Thus the investigators conduct this multicentre randomised clinical trial, comparing transanal TME versus laparoscopic TME for mid and low rectal cancer, aiming to prove the hypothesis that TaTME may achieve better resection quality and result in non-inferior oncological outcome, as well as short term operative morbidity and mortality.

Condition or Disease	Intervention/Treatment	Phase
Rectal Neoplasms Malignant Surgery	Procedure: TaTME Procedure: LpTME	N/A

Detailed Description

Background:In recent years, transanal mesorectal excision (TaTME) has emerged as a promising surgical alternative for rectal cancer, especially for mid and low rectal cancer. Theoretically, TaTME holds the potential advantage of providing better access to mobilize the distal rectum, and thus could achieve better pathologic outcomes, such as lower involved circumferential margin (CRM) and incomplete resected mesorectum, which could translate into better oncological outcome for the patients in the long term. However, until now, the feasibility and the non-inferiority (compared with laparoscopic total mesorectal excision, LpTME) of this technique has only been validated in studies with limitations of small sample size, retrospective nature.

Study Objective:This study aims to evaluate the TaTME technique compared with conventional laparoscopic rectal surgery, focusing on resection quality, as well as long-term survival results.

Study design This study is a prospective, multi-center, randomized, open-label, parallel group trial. The randomisation ratio of TaTME over LpTME will be 1:1. A central electronic data capture (EDC) system will be utilized for randomization, electronic CRF and data collection. All comparative analyses will be conducted on an "intention to treat" basis.

Sample size: Sample-size calculation of this trial based on 3-year DFS and 5-year OS; but the sample size according to 5-year OS was larger than that based on 3-year DFS. The expected 5-year OS among clinical stage I-III rectal cancer patients treated with laTME was 77·4%. Allowing a difference of 10% as the non-inferiority margin, 910 patients would be required to sufficiently declare taTME noninferior to laTME in 5-year OS based on a log-rank test with an α error of 2·5% (in a two-sided test) and power of 80%. Assuming a dropout rate of 20%, a total of 1114 patients were planned to enroll for this trial.

Study Endpoints:The primary end point of this study is 3-year disease-free survival (DFS) rate and a 5-year overall survival (OS) rate. Secondary endpoints include: 1) resection quality, mainly including circumferential involvement rate, and completeness of mesorectum. Resected specimen was pathologically processed and assessed at each center by trained and qualified pathologists independently.2)short term operative results such as morbidity and mortality, etc.; 3) long term oncological outcome such as local recurrence, and overall survival. Besides, functional outcome and quality of life are also evaluated.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Transanal or Laparoscopic Total Mesorectal Excision treat rectal cancerTransanal or Laparoscopic Total Mesorectal Excision treat rectal cancer

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Transanal Versus Laparoscopic Total Mesorectal Excision For Mid And Low Rectal Cancer (TaLaR): A Multicentre Randomised Clinical Trial

Actual Study Start Date :

Apr 1, 2016

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transanal Total Mesorectal Excision The rectum is mobilized and resected transanally (from bottom to up) according to TME principles, via transanal platform (either rigid or flexible platform).An ideal TaTME is defined as the extraperitoneal portion of the rectum being mobilized from below.	Procedure: TaTME Transanal Total Mesorectal Excision Other Names: Transanal TME
Active Comparator: Laparoscopic Total Mesorectal Excision The traditional laparoscopic TME (LpTME) was performed via standard laparoscopic techniques, including multiple trocars and conventional laparoscopic instruments.	Procedure: LpTME Conventional Laparoscopic Total Mesorectal Excision Other Names: Laparoscopic TME

Arm

Intervention/Treatment

Experimental: Transanal Total Mesorectal Excision

The rectum is mobilized and resected transanally (from bottom to up) according to TME principles, via transanal platform (either rigid or flexible platform).An ideal TaTME is defined as the extraperitoneal portion of the rectum being mobilized from below.

Procedure: TaTME

Transanal Total Mesorectal Excision

Other Names:

Transanal TME

Active Comparator: Laparoscopic Total Mesorectal Excision

The traditional laparoscopic TME (LpTME) was performed via standard laparoscopic techniques, including multiple trocars and conventional laparoscopic instruments.

Procedure: LpTME

Conventional Laparoscopic Total Mesorectal Excision

Other Names:

Laparoscopic TME

Outcome Measures

Primary Outcome Measures

Disease-free survival [3 years]
Disease-free survival
Overall survival [5 years]
Overall survival

Secondary Outcome Measures

Positive circumferential resection margin (CRM) [3 years]
Involved CRM (tumor cells <1mm)
Overall survival [10 years]
Overall survival
Mesorectal completeness [3 years]
The quality of the mesorectum or TME specimen (complete;nearly complete; incomplete)
Number of retrieved lymph nodes [3 years]
Number of retrieved lymph nodes
Morbidity rate [1 years]
Morbidity rate
Mortality rate [1 years]
Mortality rate
Anorectal function outcomes [3 years]
To evaluate defecating function with Wexner score
Sexual functional outcomes [3 years]
To evaluate sexual function with IIEF(International Index of Erectile Function) questionnaire
The patient's Quality of life: EORTC QLQ-30 questionnaire [3 years]
To evaluate quality of life with EORTC QLQ-30 questionnaire

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

histologically proven rectal adenocarcinoma;

tumor located below the level of peritoneal reflection ;

diagnosis of rectal cancer amenable to curative surgery;

no evidence of distant metastases;

preoperative tumor stage within III;

no threaten mesorectal fascia (MRF)after neoadjuvant therapy;

no contraindication to laparoscopic surgery;

without history of other malignancies;

Written informed consent

Exclusion Criteria:

could not perform sphincter preservation surgery (requiring a Mile's procedure);

T4b tumor invading adjacent organs;

T1 tumors that can be locally resected

should take neoadjuvant therapy but refuse it;

recurrent cancer;

concurrent or previous diagnosis of invasive cancer within 5 years;

emergent surgery with intestinal obstruction or perforation;

history of colorectal surgery;

fecal incontinence;

history of inflammatory bowel disease;

with contraindications to general anaesthesia(ASA class 4 or 5);

pregnant or breast-feeding;

history of mental disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences	Beijing	Beijing	China	100730
2	Department of General Surgery, Daping Hospital, Army Medical university	Chongqing	Chongqing	China	400042
3	Department of colorectal surgery, the Sixth Affiliated Hospital, Sun Yat-Sen University	Guangzhou	Guangdong	China	510000
4	Nanfang Hospital	Guangzhou	Guangdong	China	510559
5	The Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong	China	524001
6	Affiliated Hospital of Zunyi Medical University	Zunyi	Guizhou	China	563003
7	The Third Xiangya Hospital of Central South University	Changsha	Hunan	China	410013
8	The First Affiliated Hospital of University of South China	Hengyang	Hunan	China	421001
9	Department of Gastrointestinal Surgery, The First Hospital of Jilin University	Changchun	Jilin	China	130021
10	Department of Colorectal Surgery, Shengjing Hospital of China Medical University	Shenyang	Liaoning	China	110004
11	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710061
12	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200025
13	Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University,	Shanghai	Shanghai	China	200127
14	Department of Gastrointestinal Surgery，The Affiliated Nanchong Central Hospital of North Sichuan Medical College	Nanchong	Sichuan	China	637000
15	Department of gastrointestinal surgery, the Second People's Hospital of Yibin	Yibin	Sichuan	China	644000
16	XinQiao Hospital of Army Medical University	Chongqing		China	400037

Sponsors and Collaborators

Sun Yat-sen University
Peking Union Medical College Hospital
The First Hospital of Jilin University
RenJi Hospital
Shengjing Hospital
The Second People's Hospital of Yibin
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Nanchong Central Hospital
Zunyi Medical College
The First Affiliated Hospital of University of South China
Xinqiao Hospital
Nanfang Hospital of Southern Medical University
First Affiliated Hospital Xi'an Jiaotong University
Ruijin Hospital
The Affiliated Hospital of Guangdong Medical College
The Third Xiangya Hospital of Central South University