Rectal CarcinomaPhase 3COLORIIINCT02736942
COLOR III Trial: Transanal vs Laparoscopic TME
A Phase 3 study testing Laparoscopic TME and TaTME in people with Rectal Carcinoma and Surgery, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Carcinoma, Surgery
- What is being tested?
- Laparoscopic TME and TaTME
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,104 participants
- Where
- 1 siteNetherlands
- Study dates
- 2 Dec 2016to May 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Rectal Carcinoma, Surgery
- Being tested
- Laparoscopic TME, TaTME
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laparoscopic TMEProcedure or surgery
Laparoscopic Total Mesorectal Excision
TaTMEProcedure or surgery
Transanal Total Mesorectal Excision
| Study group | Role | What they receive |
|---|---|---|
| Laparoscopic | Active comparator | Laparoscopic TME Receives: Procedure: Laparoscopic TME |
| Transanal | Experimental | TaTME Receives: Procedure: TaTME |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local recurrence rate
Local recurrence rate, determined by MRI at 3 year follow-up
Measured: 3 years
Secondary outcomes (11)
Percentage of participants with involvement of circumferential resection margin (tumour cells < 1mm from circumferential resection margin)
Pathological microscopic examination of specimen
Measured: Post operative 1 month
Morbidity rate
Measured: 5 years
Mortality rate
Measured: 5 years
Percentage of participants with recurrence
Local and distant.
Measured: 5 years
Disease-free survival rate
Measured: 5 years
Overall survival rate
Measured: 5 years
Percentage of sphincter saving procedures
Measured: 4 years
Change in functional outcomes (LARS questionnaire)
Measured by questionnaires
Measured: Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-29 questionnaire)
Measured by questionnaires
Measured: Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-30 questionnaire)
Measured by questionnaires
Measured: Baseline and 1 year
Change in Health Related Quality of Life (EQ 5-D questionnaire)
Measured by questionnaires
Measured: Baseline and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study start2 Dec 2016
- Primary completionMay 2021 (estimated)
- Study completionMay 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CarcinomaStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.J. Bonjer, Amsterdam UMC, location VUmc
- Investigators
- Hendrik J. Bonjer, MD, PhD, Principal investigator, Amsterdam UMC, location VUmcAntonio M. Lacy, MD, PhD, Principal investigator, Hospital Clinic of BarcelonaGeorge B. Hanna, MD, PhD, Principal investigator, Imperial College LondonJurriaan B. Tuynman, MD, PhD, Study director, Amsterdam UMC, location VUmcColin Sietses, MD, PhD, Study director, Gelderse Vallei Hospital Ede
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02736942
- Sponsor's protocol ID
- 2015.449
- Acronym
- COLORIII
- Status last verified
- Jun 2019
- First submitted
- 18 Feb 2016
- Last updated
- 6 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: We are not sharing confidential individual patient data.
Publications
Tuynman JB, Yao H, Moolenaar LR, Sietses C, Hompes R, Aigner F, Caycedo-Marulanda A, Chen CC, Deeb M, Doornebosch PG, Feng B, Foo CC, Furst A, Ito M, de Lacy FB, Leao P, Maykel JA, Muratore A, van Oostendorp SE, Park SC, Pedziwiatr M, Ren M, Seitinger G, Stockmann HBAC, Talsma AK, Turler A, Tong W, Wang Q, Xu Q, Zhang H, van Waesberghe JTM, Ali M, Twisk JWR, Zhang Z, de Lacy AM, Hanna GB, Bonjer HJ; COLOR III Study Group. Transanal total mesorectal excision versus laparoscopic total mesorectal excision for mid and low rectal cancer (COLOR III): short-term outcomes of an international, multicentre, phase 3, randomised, controlled, non-inferiority trial. Lancet Gastroenterol Hepatol. 2026 May;11(5):355-366. doi: 10.1016/S2468-1253(26)00022-1. Epub 2026 Mar 23.
PubMed 41887239
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COLOR III: A Multicentre Randomised Clinical Trial Comparing Transanal TME Versus Laparoscopic TME for Mid and Low Rectal Cancer
- ClinicalTrials.gov ID
- NCT02736942
- Acronym / sponsor ID
- COLORIII / 2015.449
- Conditions
- Rectal Carcinoma, Surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,104 participants (estimated)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- 2 Dec 2016 (actual)
- Primary completion
- May 2021 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 13 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Laparoscopic | Active comparator | Procedure: Laparoscopic TMELaparoscopic TME |
| Transanal | Experimental | Procedure: TaTMETaTME |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laparoscopic TMELaparoscopic Total Mesorectal Excision | Procedure or surgery | Laparoscopic |
| TaTMETransanal Total Mesorectal Excision | Procedure or surgery | Transanal |
Primary outcome
Local recurrence rate
Time frame: 3 years
Local recurrence rate, determined by MRI at 3 year follow-up
11 secondary outcomes
Percentage of participants with involvement of circumferential resection margin (tumour cells < 1mm from circumferential resection margin)
Time frame: Post operative 1 month
Morbidity rate
Time frame: 5 years
Mortality rate
Time frame: 5 years
Percentage of participants with recurrence
Time frame: 5 years
Disease-free survival rate
Time frame: 5 years
Overall survival rate
Time frame: 5 years
Percentage of sphincter saving procedures
Time frame: 4 years
Change in functional outcomes (LARS questionnaire)
Time frame: Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-29 questionnaire)
Time frame: Baseline and 1 year
Change in Health Related Quality of Life (EORTC QLQ-30 questionnaire)
Time frame: Baseline and 1 year
Change in Health Related Quality of Life (EQ 5-D questionnaire)
Time frame: Baseline and 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2019.
- Derived from this study: PubMed 41887239Tuynman JB, Yao H, Moolenaar LR, Sietses C, Hompes R, Aigner F, Caycedo-Marulanda A, Chen CC, Deeb M, Doornebosch PG, Feng B, Foo CC, Furst A, Ito M, de Lacy FB, Leao P, Maykel JA, Muratore A, van Oostendorp SE, Park SC, Pedziwiatr M, Ren M, Seitinger G, Stockmann HBAC, Talsma AK, Turler A, Tong W, Wang Q, Xu Q, Zhang H, van Waesberghe JTM, Ali M, Twisk JWR, Zhang Z, de Lacy AM, Hanna GB, Bonjer HJ; COLOR III Study Group. Transanal total mesorectal excision versus laparoscopic total mesorectal excision for mid and low rectal cancer (COLOR III): short-term outcomes of an international, multicentre, phase 3, randomised, controlled, non-inferiority trial. Lancet Gastroenterol Hepatol. 2026 May;11(5):355-366. doi: 10.1016/S2468-1253(26)00022-1. Epub 2026 Mar 23.
- Official trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No. We are not sharing confidential individual patient data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hendrik J. Bonjer, MD, PhD principal investigator
Amsterdam UMC, location VUmc
Antonio M. Lacy, MD, PhD principal investigator
Hospital Clinic of Barcelona
George B. Hanna, MD, PhD principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Laparoscopic TME and TaTME in people with Rectal Carcinoma and Surgery, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local recurrence rate (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02736942, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2019.