COLOR III Trial: Transanal vs Laparoscopic TME (COLORIII)

COLOR III: A Multicentre Randomised Clinical Trial Comparing Transanal TME Versus Laparoscopic TME for Mid and Low Rectal Cancer

Background Surgery for mid and low rectal cancer is associated with relative high rates of incomplete mesorectal excisions and high rates of circumferential resection margin (CRM) involvement resulting in significant number of local recurrences. Moreover, patients with mid and low rectal cancer suffer from high rates of morbidity, permanent colostomies and impairment of quality of life. The transanal TME (TaTME) has been developed to improve the quality of TME surgery in mid and low rectal cancer.

Study design The COLOR III trial is an international multicentre randomised study comparing short- and long-term outcomes of TaTME and laparoscopic TME for rectal cancer. The study will include a quality assessment phase before randomisation to ensure required competency level and uniformity of the new TaTME technique and the laparoscopic TME. During the trial clinical data will be reviewed centrally to ensure uniform quality.

Endpoints The primary endpoint of the study is the local recurrence rate at 3-years follow-up. Secondary endpoints include sphincter saving procedures, short-term morbidity and mortality, involved circumferential resection margin (CRM), disease-free and overall survival at 3 and 5 years, completeness of mesorectum and quality of life.

Statistics In laparoscopic TME the percentage of local recurrence at 3-years follow-up is estimated 5%. With the non-inferiority margin set at 4%, with a one-sided level of significance of 2.5% and a power of 80%, a total of 1104 patients is needed, 669 patients in the TaTME arm and 335 patients in the laparoscopic TME arm. All analyses will be performed on intention-to-treat basis.

Main selection criteria Patients with histologically proven single mid or distal rectum carcinoma (0 to 10 cm from anal verge) at MRI, eligible for restorative surgery with a curative intent, are included. Patients with a T1 tumor suitable for local excision, T3 tumors with a suspected involved circumferential resection margin and T4 tumors are excluded.

Hypothesis The hypothesis is that TaTME will result in a comparable local recurrence rate at 3-years follow-up with benefit of lower morbidity and conversions. Furthermore, because of direct endoscopic visualization, even in very low tumors a coloanal anastomosis can be created, resulting in a lower colostomy rate compared with laparoscopic and open resection. Because long-term outcomes are unknown, within a trial setting the technique can be standardized and quality control can be performed.

Study Overview

• Status: Enrolling by invitation
• Conditions: Surgery; Rectal Carcinoma
• Intervention / Treatment: Procedure: Laparoscopic TME; Procedure: TaTME

Detailed Description

To improve oncological and functional outcomes of patients with rectal cancer new surgical techniques are being developed. The adoption of the TME technique has resulted in better oncological outcome in the last decades. The addition of neoadjuvant therapy has further improved oncological outcome. The minimal invasive laparoscopic resection of rectal cancer has shown to be safe and to result in improved short-term outcomes and reduced morbidity.

Nevertheless, the laparoscopic resection of mid and low rectal cancer remains challenging due to the anatomy of the narrow pelvis and is associated with a relative high risk of resections with an involved CRM resulting in increased risk of a local recurrence.

In attempt to improve the quality of the TME procedure in low rectal cancer and further improve oncological results the TaTME has been developed, in which the rectum is dissected transanally according to TME principles. First series have been described since 2010 and although randomised evidence is still lacking this new technique has shown to be feasible and safe. The rectum including the total mesorectum is mobilised transanally in a reversed way with minimally invasive surgery including high quality imaging techniques.

The TaTME technique for mid and low rectal cancer has shown to have potential benefits: better specimen quality with less R1 resections, less morbidity, less conversion to laparotomy and more sphincter saving rectal resections without compromising oncological outcomes.

The investigators propose to evaluate the TaTME technique compared with conventional laparoscopic rectal resection for patients with mid and low rectal cancer in an international randomised trial: the COLOR III trial.

• Study Type: Interventional
• Enrollment (Anticipated): 1104
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Solitary mid (5.1-10cm from anal verge on MRI) or low (0-5cm from anal verge on MRI) rectal cancer observed at colonoscopy and histologically proven through biopsy
• Distal border of the tumour within 10cm from the anal verge on MRI-scan
• Tumour with threatened margins downstaged after neoadjuvant therapy to free margins
• No evidence for distal metastases on imaging of thorax and abdomen
• Suitable for elective surgical resection
• Informed consent according to local requirements

Exclusion Criteria:

• T3 tumours with margins less than 1mm to the MRF, determined by MRI-scan (as staged after preoperative chemo- and/or radiotherapy)
• T4 tumours, as staged after preoperative chemo- and/or radiotherapy
• Tumours with in growth more than 1/3 of anal sphincter complex or levator ani
• Malignancy other than adenocarcinoma at histological examination
• Patients under 18 years of age
• Pregnancy
• Previous rectal surgery (excluding local excision, EMR (endoscopic mucosal resection) or polypectomy)
• Signs of acute intestinal obstruction
• Multiple colorectal tumours
• Familial Adenomatosis Polyposis Coli (FAP), Hereditary Non-Polyposis Colorectal Cancer (HNPCC), active Crohn's disease or active ulcerative colitis
• Planned synchronous abdominal organ resections
• Preoperative suspicion of invasion of adjacent organs through MRI-scan
• Preoperative evidence for distant metastases through imaging of the thorax and abdomen
• Other malignancies in medical history, except adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri
• Absolute contraindications to general anaesthesia or prolonged pneumoperitoneum, as severe cardiovascular or respiratory disease (ASA class > III)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Laparoscopic; Laparoscopic TME	Procedure: Laparoscopic TME; Laparoscopic Total Mesorectal Excision
Experimental: Transanal; TaTME	Procedure: TaTME; Transanal Total Mesorectal Excision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence rate	Local recurrence rate, determined by MRI at 3 year follow-up	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate		5 years
Percentage of participants with involvement of circumferential resection margin (tumour cells < 1mm from circumferential resection margin)	Pathological microscopic examination of specimen	Post operative 1 month
Morbidity rate		5 years
Mortality rate		5 years
Percentage of participants with recurrence	Local and distant.	5 years
Disease-free survival rate		5 years
Percentage of sphincter saving procedures		4 years
Change in functional outcomes (LARS questionnaire)	Measured by questionnaires	Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-29 questionnaire)	Measured by questionnaires	Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-30 questionnaire)	Measured by questionnaires	Baseline and 1 year
Change in Health Related Quality of Life (EQ 5-D questionnaire)	Measured by questionnaires	Baseline and 1 year

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Hendrik J. Bonjer, MD, PhD, Amsterdam Umc, Location Vumc; Principal Investigator: Antonio M. Lacy, MD, PhD, Hospital Clinic of Barcelona; Principal Investigator: George B. Hanna, MD, PhD, Imperial College London; Study Director: Jurriaan B. Tuynman, MD, PhD, Amsterdam Umc, Location Vumc; Study Director: Colin Sietses, MD, PhD, Gelderse Vallei Hospital Ede

Publications and helpful links

Helpful Links

• Official trial website

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2016
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2025

Study Registration Dates

• First Submitted: February 18, 2016
• First Submitted That Met QC Criteria: April 7, 2016
• First Posted (Estimate): April 13, 2016

Study Record Updates

• Last Update Posted (Actual): June 6, 2019
• Last Update Submitted That Met QC Criteria: June 4, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2015.449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We are not sharing confidential individual patient data.