Colon CancerPhase 2/3NCT02526836
Complete Mesocolic Excision With Central Vessel Ligation Compared With Conventional Surgery for Colon Cancer
A Phase 2/3 study testing Conventional Surgery and Complete mesocolic excision with central vascular ligation in people with Colon Cancer, run by Mansoura University at 2 sites in 2 countries.
Trial summary
The aim of this study is to compare between complete mesocolic excision with central vascular ligation and conventional surgery of colon cancer regarding number of harvested lymph nodes, surgical outcome and complications. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer
- What is being tested?
- Conventional Surgery and Complete mesocolic excision with central vascular ligation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Sep 2014to Oct 2018
- Phase
- Phase 2/3
- 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
- Pathologically proven adenocarcinoma (including mucinous and signet-ring cell) or adenosquamous carcinoma on endoscopic biopsy.
- Tumor localization at the caecum, ascending colon, transverse colon, descending colon, sigmoid colon or rectosigmoid on preoperative endoscopy and radiographic imaging [barium enema or computed tomography (CT)] without location of the lower border of the tumor at the rectum.
- No history of familial adenomatous polyposis, ulcerative colitis or Crohn's disease.
- Body mass index ≤ 35.
- Sufficient organ function including cardiovascular system and liver.
- Written informed consent.
Who cannot join
- Contraindications to major surgery and American Society of Anesthesiologists (ASA) Physical Status scoring 4 which means extreme systemic disorders which have already become an eminent threat to life regardless of the type of treatment.
- Infectious disease requiring treatment.
- Body temperature ≥ 38 °C.
- Pregnant women.
- History of psychiatric disease.
- Use of systemic steroids.
- History of myocardial infarction or unstable angina pectoris within 6 months.
- Severe pulmonary emphysema or pulmonary fibrosis
Trial locations and contacts
2 sites in 2 countries.
Ahmed Setit, MD contact
2 sites in 2 countries
Egypt1 site, 1 recruiting
- Recruiting
Oncology Center Mansoura University (OCMU), Egypt
Al Mansurah, Dakahlia Governorate, 35516
Mohamed Abdelkhalek, M.Sc, +201001850214, mabdelkhalek@mans.edu.eg
Ahmed Setit, MD, asetit@mans.edu.eg
Italy1 site, 1 recruiting
- Recruiting
National Cancer Institute "Fond. G. Pascale"
Naples, 80131
Giovanni Romano, MD, +39 081 5903 311, gromano53@katamail.com
About this study
Official title: Complete Mesocolic Excision (CME) With Central Supplying Vessel Ligation (CVL) Compared With Conventional Surgery for Colon Cancer: a Double-blinded Randomized Study
The aim of this study is to compare between complete mesocolic excision with central vascular ligation and conventional surgery of colon cancer regarding number of harvested lymph nodes, surgical outcome and complications.
Read the detailed description
Colorectal cancer is the third most common human malignant epithelial tumor and still represents the second cause of cancer death in the United States and Europe.
Over the past few decades, there have been significant improvements in the treatment of patients with colonic and rectal cancers. In rectal cancer, the role of earlier diagnosis, improved preoperative staging, neoadjuvant therapy and total mesorectal excision have improved outcomes from oncological and patient recovery perspectives. Of these, arguably the most important for the surgeon was the advent of Total Mesorectal Excision (TME).
Current thinking is that colonic tumors spread via hematogenous, lymphatic, and possibly perineural routes, with the lymphatics anatomically following the arterial supply. Current practice is to excise a proportion of the draining lymphatic bed to accurately stage the cancer and also clear possible lymphatic metastases.
Recently, significant debate has centered on the degree of lymphatic clearance required; several reports have demonstrated improved oncologic outcomes with wider lymphovascular resections compared with current standard practice. Whether these improved outcomes are secondary to improved lymph node yield or an alternative technical effect has not yet been ascertained.
In analogy to total mesorectal excision (TME) for rectal cancer complete mesocolic excision was recently introduced for curative treatment of colon cancer. Like TME, CME aims at complete en bloc clearance of the lymphatic drainage of the tumor enveloped in intact fascias of embryologic origin.
Based on total mesorectal excision experience, further investigations of the importance of complete mesocolic excision and central vascular ligation surgery for colonic cancer were done by comparing a series of complete mesocolic excision and central vascular ligation specimens from Erlangen, Germany to standard excisions from Leeds, United Kingdom. Lymph node yields, tissue morphometry, and grading the plane of surgery were used to investigate differences between the techniques that could potentially explain the relative differences in survival.
The group from Erlangen in Germany have advocated for CME in conjunction with central vascular ligation for colon cancer. Complete mesocolic excision is reported to differ from traditional colon cancer surgery by achieving a far more radical excision of the lymphovascular pedicle and mesocolon. In addition, the complete mesocolic excision technique promotes resection of the specimen with an intact visceral peritoneum together with proximal and distal resection margins of at least 10 cm. Arterial supply to the affected segment of bowel is taken at its origin from the superior mesenteric artery (right and transverse colon) and the aorta (left colon), described as central vascular ligation. Complete mesocolic excision has been shown to lead to increased lymph node harvest and more mesocolic tissue.
In a comparison between the Leeds and Erlangen units, it was shown that complete mesocolic excision led to an almost doubling in both the number of lymph nodes retrieved and area of mesentery resected. However, a Danish study showed only a 9% increase in lymph node yield.
Surgical concept of complete mesocolic excision represents sharp separation of the undamaged visceral fascia of mesocolon from parietal fascia of peritoneum and the end goal is mobilization of mesocolon and the approach to the appropriate vascular bundle. The scope of surgical intervention depends on localization of the tumor itself. In case that the tumor is located in the right colon next to caecum and ascending colon, it also implies the elevation of duodenum and the head of pancreas (Kocher maneuver) and access to the upper mesenteric vein and artery and its branches. For tumors of the left colon, mobilization of sigma and descending colon is necessary, total separation from the parietal peritoneum, urethra, testicular or ovarian blood vessels, as well as separation from the kidney fat tissue.
The apparent improved outcomes with complete mesocolic excision are yet to be confirmed with a formal Randomized Controlled Trial (RCT). Proposed explanations for the apparent improvements are that increasing lymph node yield permits stage migration, that increased lymph node yield removes a source of metastases, and that it has nothing to do with lymphatics but is due to the preservation of an intact peritoneum.
- Conditions
- Colon Cancer
- Being tested
- Conventional Surgery, Complete mesocolic excision with central vascular ligation
- Keywords
- colon cancer mesocolic excision central ligation
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conventional SurgeryProcedure or surgery
removal of the tumor with no ligation of the vessel centrally or removal of the whole mesocolon
Complete mesocolic excision with central vascular ligationProcedure or surgery
excision of the whole mesocolon plus ligation of the supplying blood vessel centrally
| Study group | Role | What they receive |
|---|---|---|
| Comparison group | Other | including the number of cases with complete data who underwent surgery using the conventional method.
Conventional surgery Receives: Procedure: Conventional Surgery |
| Intervention group | Active comparator | including a convenient sample of about 20 patients which is expected to be recruited, for whom Complete Mesocolic Excision (CME) and Central Vascular Ligation (CVL) will be done.
Complete mesocolic excision with central vascular ligation Receives: Procedure: Complete mesocolic excision with central vascular ligation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lymph nodes harvest
Number of retrieved lymph nodes
Measured: Day of surgery
Secondary outcomes (4)
Oncologic outcome
Number of patients with local or distant recurrence after the surgery.
Measured: 2 years
Operative outcome
A composite outcome of the Operative time, blood loss, blood transfusion, intraoperative morbidities and mortality
Measured: Day of suregry
Postoperative outcome
A composite outcome of the number of morbidities and mortalities in the postoperative setting
Measured: 1 month
Survival outcome
Number of patients with 2 year free survival
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2015 (estimated)
- Study startSep 2014
- Primary completionSep 2018 (estimated)
- Study completionOct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colon CancerStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mansoura University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohamed Abdelkhalek, Mansoura University
- Investigators
- Mohamed Abdelkhalek, M.Sc, Principal investigator, Oncology Center Mansoura University (OCMU), EgyptGiovanni Romano, MD, Principal investigator, National Cancer Institute "Fond. G. Pascale", ItalyAdel Denewer, MD, Study chair, Oncology Center Mansoura University (OCMU), EgyptTamer F Youssef, MD, Study director, Oncology Center Mansoura University (OCMU), Egypt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02526836
- Sponsor's protocol ID
- Complete Mesocolic Excision
- Status last verified
- Nov 2017
- First submitted
- 11 Aug 2015
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Yes
Publications
Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome. Colorectal Dis. 2009 May;11(4):354-64; discussion 364-5. doi: 10.1111/j.1463-1318.2008.01735.x. Epub 2009 Nov 5.
PubMed 19016817Bertelsen CA, Neuenschwander AU, Jansen JE, Wilhelmsen M, Kirkegaard-Klitbo A, Tenma JR, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Iversen ER, Kristensen B, Gogenur I; Danish Colorectal Cancer Group. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study. Lancet Oncol. 2015 Feb;16(2):161-8. doi: 10.1016/S1470-2045(14)71168-4. Epub 2014 Dec 31.
PubMed 25555421
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Complete Mesocolic Excision (CME) With Central Supplying Vessel Ligation (CVL) Compared With Conventional Surgery for Colon Cancer: a Double-blinded Randomized Study
- ClinicalTrials.gov ID
- NCT02526836
- Acronym / sponsor ID
- Complete Mesocolic Excision
- Conditions
- Colon Cancer
- Keywords
- colon cancer mesocolic excision central ligation
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Mansoura UniversityUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Oct 2018 (estimated)
- First posted
- 18 Aug 2015 (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.
The aim of this study is to compare between complete mesocolic excision with central vascular ligation and conventional surgery of colon cancer regarding number of harvested lymph nodes, surgical outcome and complications.
Detailed description
Colorectal cancer is the third most common human malignant epithelial tumor and still represents the second cause of cancer death in the United States and Europe.
Over the past few decades, there have been significant improvements in the treatment of patients with colonic and rectal cancers. In rectal cancer, the role of earlier diagnosis, improved preoperative staging, neoadjuvant therapy and total mesorectal excision have improved outcomes from oncological and patient recovery perspectives. Of these, arguably the most important for the surgeon was the advent of Total Mesorectal Excision (TME).
Current thinking is that colonic tumors spread via hematogenous, lymphatic, and possibly perineural routes, with the lymphatics anatomically following the arterial supply. Current practice is to excise a proportion of the draining lymphatic bed to accurately stage the cancer and also clear possible lymphatic metastases.
Recently, significant debate has centered on the degree of lymphatic clearance required; several reports have demonstrated improved oncologic outcomes with wider lymphovascular resections compared with current standard practice. Whether these improved outcomes are secondary to improved lymph node yield or an alternative technical effect has not yet been ascertained.
In analogy to total mesorectal excision (TME) for rectal cancer complete mesocolic excision was recently introduced for curative treatment of colon cancer. Like TME, CME aims at complete en bloc clearance of the lymphatic drainage of the tumor enveloped in intact fascias of embryologic origin.
Based on total mesorectal excision experience, further investigations of the importance of complete mesocolic excision and central vascular ligation surgery for colonic cancer were done by comparing a series of complete mesocolic excision and central vascular ligation specimens from Erlangen, Germany to standard excisions from Leeds, United Kingdom. Lymph node yields, tissue morphometry, and grading the plane of surgery were used to investigate differences between the techniques that could potentially explain the relative differences in survival.
The group from Erlangen in Germany have advocated for CME in conjunction with central vascular ligation for colon cancer. Complete mesocolic excision is reported to differ from traditional colon cancer surgery by achieving a far more radical excision of the lymphovascular pedicle and mesocolon. In addition, the complete mesocolic excision technique promotes resection of the specimen with an intact visceral peritoneum together with proximal and distal resection margins of at least 10 cm. Arterial supply to the affected segment of bowel is taken at its origin from the superior mesenteric artery (right and transverse colon) and the aorta (left colon), described as central vascular ligation. Complete mesocolic excision has been shown to lead to increased lymph node harvest and more mesocolic tissue.
In a comparison between the Leeds and Erlangen units, it was shown that complete mesocolic excision led to an almost doubling in both the number of lymph nodes retrieved and area of mesentery resected. However, a Danish study showed only a 9% increase in lymph node yield.
Surgical concept of complete mesocolic excision represents sharp separation of the undamaged visceral fascia of mesocolon from parietal fascia of peritoneum and the end goal is mobilization of mesocolon and the approach to the appropriate vascular bundle. The scope of surgical intervention depends on localization of the tumor itself. In case that the tumor is located in the right colon next to caecum and ascending colon, it also implies the elevation of duodenum and the head of pancreas (Kocher maneuver) and access to the upper mesenteric vein and artery and its branches. For tumors of the left colon, mobilization of sigma and descending colon is necessary, total separation from the parietal peritoneum, urethra, testicular or ovarian blood vessels, as well as separation from the kidney fat tissue.
The apparent improved outcomes with complete mesocolic excision are yet to be confirmed with a formal Randomized Controlled Trial (RCT). Proposed explanations for the apparent improvements are that increasing lymph node yield permits stage migration, that increased lymph node yield removes a source of metastases, and that it has nothing to do with lymphatics but is due to the preservation of an intact peritoneum.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Comparison group | Other | Procedure: Conventional Surgeryincluding the number of cases with complete data who underwent surgery using the conventional method. Conventional surgery |
| Intervention group | Active comparator | Procedure: Complete mesocolic excision with central vascular ligationincluding a convenient sample of about 20 patients which is expected to be recruited, for whom Complete Mesocolic Excision (CME) and Central Vascular Ligation (CVL) will be done. Complete mesocolic excision with central vascular ligation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pathologically proven adenocarcinoma (including mucinous and signet-ring cell) or adenosquamous carcinoma on endoscopic biopsy.
- Tumor localization at the caecum, ascending colon, transverse colon, descending colon, sigmoid colon or rectosigmoid on preoperative endoscopy and radiographic imaging [barium enema or computed tomography (CT)] without location of the lower border of the tumor at the rectum.
- No history of familial adenomatous polyposis, ulcerative colitis or Crohn's disease.
- Body mass index ≤ 35.
- Sufficient organ function including cardiovascular system and liver.
Key exclusion criteria (8 listed)
- Contraindications to major surgery and American Society of Anesthesiologists (ASA) Physical Status scoring 4 which means extreme systemic disorders which have already become an eminent threat to life regardless of the type of treatment.
- Infectious disease requiring treatment.
- Body temperature ≥ 38 °C.
- Pregnant women.
- History of psychiatric disease.
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 |
|---|---|---|
| Conventional Surgeryremoval of the tumor with no ligation of the vessel centrally or removal of the whole mesocolon | Procedure or surgery | Comparison group |
| Complete mesocolic excision with central vascular ligationexcision of the whole mesocolon plus ligation of the supplying blood vessel centrally | Procedure or surgery | Intervention group |
Primary outcome
Lymph nodes harvest
Time frame: Day of surgery
Number of retrieved lymph nodes
4 secondary outcomes
Oncologic outcome
Time frame: 2 years
Operative outcome
Time frame: Day of suregry
Postoperative outcome
Time frame: 1 month
Survival outcome
Time frame: 3 Years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
- Background: PubMed 19016817Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome. Colorectal Dis. 2009 May;11(4):354-64; discussion 364-5. doi: 10.1111/j.1463-1318.2008.01735.x. Epub 2009 Nov 5.
- Background: PubMed 25555421Bertelsen CA, Neuenschwander AU, Jansen JE, Wilhelmsen M, Kirkegaard-Klitbo A, Tenma JR, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Iversen ER, Kristensen B, Gogenur I; Danish Colorectal Cancer Group. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study. Lancet Oncol. 2015 Feb;16(2):161-8. doi: 10.1016/S1470-2045(14)71168-4. Epub 2014 Dec 31.
- Individual participant dataSharing planned: Yes. Yes
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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.
Ahmed Setit, MD contact
Mohamed Abdelkhalek, M.Sc principal investigator
Oncology Center Mansoura University (OCMU), Egypt
Giovanni Romano, MD principal investigator
National Cancer Institute "Fond. G. Pascale", Italy
Adel Denewer, MD study chair
Oncology Center Mansoura University (OCMU), Egypt
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Conventional Surgery and Complete mesocolic excision with central vascular ligation in people with Colon Cancer, run by Mansoura University at 2 sites in 2 countries.
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 8 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 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Egypt, Italy. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Mohamed Abdelkhalek, M.Sc (+201001850214, mabdelkhalek@mans.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lymph nodes harvest (time frame: Day of surgery). 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 NCT02526836, which also lists 2 linked publications.
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 16 Aug 2018.