Clinical trial NCT02736942: COLOR III Trial: Transanal vs Laparoscopic TME
Official title: COLOR III: A Multicentre Randomised Clinical Trial Comparing Transanal TME Versus Laparoscopic TME for Mid and Low Rectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Carcinoma
Surgery
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2016-04-13
Enrollment: 1104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Local recurrence rate
timeFrame: 3 years
Secondary outcomes:
measure: Percentage of participants with involvement of circumferential resection margin (tumour cells < 1mm from circumferential resection margin)
timeFrame: Post operative 1 month
measure: Morbidity rate
timeFrame: 5 years
measure: Mortality rate
timeFrame: 5 years
measure: Percentage of participants with recurrence
timeFrame: 5 years
measure: Disease-free survival rate
timeFrame: 5 years
measure: Overall survival rate
timeFrame: 5 years
measure: Percentage of sphincter saving procedures
timeFrame: 4 years
measure: Change in functional outcomes (LARS questionnaire)
timeFrame: Baseline and 1 year
measure: Change in Health Related Quality of Life (EORTC QLQ-29 questionnaire)
timeFrame: Baseline and 1 year
measure: Change in Health Related Quality of Life (EORTC QLQ-30 questionnaire)
timeFrame: Baseline and 1 year
measure: Change in Health Related Quality of Life (EQ 5-D questionnaire)
timeFrame: Baseline and 1 year
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Hendrik J. Bonjer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Clinic of Barcelona
name: Antonio M. Lacy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: George B. Hanna, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, location VUmc
name: Jurriaan B. Tuynman, MD, PhD
role: STUDY_DIRECTOR
affiliation: Gelderse Vallei Hospital Ede
name: Colin Sietses, MD, PhD
role: STUDY_DIRECTOR
References: