Complete Mesocolic Excision in Comparison With Conventional Surgery for the Right Colon Cancer

Colon Cancer Clinical Trial

— CoME-In  

Official title:

Complete Mesocolic Excision With Central Vascular Ligation in Comparison With Conventional Surgery for the Right Colon Cancer: An Italian Randomized Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04871399
• Other study ID #: N.110/2019/U
• Status: Recruiting
• Phase: N/A
• Start date: July 13, 2020
• Est. completion date: January 1, 2027

Study information

• Verified date: September 2022
• Source: University of Turin, Italy
• Contact: Mario Solej, MD
• Phone: 00393388624939
• Email: mariosolej[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An Italian randomized controlled trial parallel-group in patients with a malignant tumor of the right or proximal transverse colon requiring right hemicolectomy.

Description:

This study aims to compare the Complete Mesocolic Excision With Central Vascular Ligation (CME+CVL) with the standard (non-CME) right hemicolectomy in patients with right or proximal transverse colon cancer stage II-IV(AJCC 8th edition) to determine the short and long term outcomes in terms of disease-free survival (DFS) as a primary endpoint, and safety, oncologic outcomes, quality of surgery and quality of life (QoL) as secondary endpoints.

Eligible patients will be randomized with a 1:1 ratio between CME + CVL vs standard non-CME right colectomy. The randomization sequence will be generated centrally by a computed algorithm and kept concealed to investigators.

The Right colectomy with CME + CVL includes the removal of the accessory lymphovascular supply at their origins by resecting the colon and mesocolon in an intact envelope of visceral peritoneum and mesenteric fascia. Despite the surgical approach and the type of procedure adopted, the operation should be strictly conducted following the general rules for colorectal oncologic resection, particularly as concerns proximal and distal margins length and lymph node retrieval.

All surgical approaches (open, laparoscopic, or robotic) will be allowed while the type of anastomosis performed and drain placement will be up to the surgeon's discretion.

Demographic, baseline, perioperative and postoperative characteristics will be analyzed as well.

The study expected to last six and a half years, of which one and a half years for recruiting 416 patients, 208 each arm, with five years of follow-up. Patients will be followed up at 1, 4, 12, 24, 36, and 60 months postoperatively.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 416
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists(ASA) grade I-III.

• Right colon cancer (*The right-sided location of the cancer is defined as the location from the caecum up to the proximal third of the transverse colon), preoperative assessment of tumor stage T2-T4a, any N or T any N+ according to the National Comprehensive Cancer Network(NCCN) clinical practice guidelines in oncology: colon cancer version 2.2015); no distant metastasis.

• Informed consent

Exclusion Criteria:

• Age > 85 years old.

• T1, N0

• T4b, any N

• BMI > 30.

• Metastatic disease (Abdominal and chest CT scan will be mandatory to exclude distant metastasis.)

• American Society of Anesthesiologists(ASA) grade IV.

• History of cancer in recent 5 years.

• Need for Emergency surgery.

• Infectious disease requiring treatment.

• Pregnancy.

• Use of systemic steroids.

• No history of familial adenomatous polyposis, ulcerative colitis or Crohn's disease.

Related Conditions & MeSH terms

• Colon Cancer
• Colonic Neoplasms

Intervention

Procedure:
• Conventional Right hemicolectomy (Non-CME)
Transecting the Ileocolic Vein and Artery close to the Superior Mesenteric Vessels without clearing the superior mesenteric vein (SMV) from the adipose tissue. Transecting the Right Colic Vein and Artery and superior right colic vein (when present) peripherally. Transecting the Right branches of the Middle Colic Vein (MCV) and the Middle Colic Artery (MCA) peripherally, without clearing the main trunk of the MCV and the MCA. The Right Gastroepiploic Vein and artery are never transacted.
• Right hemicolectomy with CME+CVL
Separation of the visceral fascia from the parietal fascia by sharp dissection leaving intact mesocolon coverage. Transecting the supplying vessels at their origin from the main vessels, particularly: The Ileocolic Vessels, The Right Colic Vessels,The superior right colic vein (when present), The Right branches of the Middle Colic Vein and of the Middle Colic Artery The MCV and MCA at their origin in case of cancer of the hepatic flexure or of the proximal third of the transverse colon, as well as The Right Gastroepiploic Vessels at their origin from the gastrocolic trunk of Henle (GCTH) and the gastroduodenal artery. The SMV should be cleared from all adipose tissue all along its anterior surface until its intrapancreatic entrance.

Locations

Country	Name	City	State
Italy	Maggiore Bellaria Hospital, Bologna	Bologna
Italy	Candiolo Cancer Institute - IRCCS	Candiolo	Torino
Italy	Università degli Studi di Ferrara	Ferrara
Italy	Ospedale Policlinico San Martino	Genova
Italy	Ospedale della Misericordia	Grosseto	Arezzo
Italy	S. Andrea Hospital	La Spezia	Spezia
Italy	Azienda Ospedaliera Universitaria Policlinico "G. Martino"	Messina
Italy	European Institute of Oncology	Milano
Italy	Federico II University	Napoli
Italy	Ospedale E. Agnelli Pinerolo	Pinerolo	Torino
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome
Italy	University of Rome Tor Vergata	Rome
Italy	Ospedale Città di Sesto San Giovanni	Sesto San Giovanni	Milano
Italy	University of Turin (AOU.San Luigi Gonzaga)	Torino

Sponsors (13)

Lead Sponsor

Collaborator

University of Turin, Italy

Agnelli Hospital, Italy, Azienda Ospedaliera Universitaria Policlinico "G. Martino", Candiolo Cancer Institute - IRCCS, European Institute of Oncology, Federico II University, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Maggiore Bellaria Hospital, Bologna, Ospedale della Misericordia, Ospedale Policlinico San Martino, S. Andrea Hospital, Università degli Studi di Ferrara, University of Rome Tor Vergata

Country where clinical trial is conducted

Italy, 

References & Publications (8)

Benz S, Tannapfel A, Tam Y, Grünenwald A, Vollmer S, Stricker I. Proposal of a new classification system for complete mesocolic excison in right-sided colon cancer. Tech Coloproctol. 2019 Mar;23(3):251-257. doi: 10.1007/s10151-019-01949-4. Epub 2019 Mar 5. — View Citation

Bertelsen CA, Bols B, Ingeholm P, Jansen JE, Neuenschwander AU, Vilandt J. Can the quality of colonic surgery be improved by standardization of surgical technique with complete mesocolic excision? Colorectal Dis. 2011 Oct;13(10):1123-9. doi: 10.1111/j.1463-1318.2010.02474.x. — View Citation

Bertelsen CA. Complete mesocolic excision an assessment of feasibility and outcome. Dan Med J. 2017 Feb;64(2). pii: B5334. Review. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Galizia G, Lieto E, De Vita F, Ferraraccio F, Zamboli A, Mabilia A, Auricchio A, Castellano P, Napolitano V, Orditura M. Is complete mesocolic excision with central vascular ligation safe and effective in the surgical treatment of right-sided colon cancers? A prospective study. Int J Colorectal Dis. 2014 Jan;29(1):89-97. doi: 10.1007/s00384-013-1766-x. Epub 2013 Aug 28. — View Citation

Johnson PM, Porter GA, Ricciardi R, Baxter NN. Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. J Clin Oncol. 2006 Aug 1;24(22):3570-5. — View Citation

Kim NK, Kim YW, Han YD, Cho MS, Hur H, Min BS, Lee KY. Complete mesocolic excision and central vascular ligation for colon cancer: Principle, anatomy, surgical technique, and outcomes. Surg Oncol. 2016 Sep;25(3):252-62. doi: 10.1016/j.suronc.2016.05.009. Epub 2016 May 20. Review. — View Citation

West NP, Kobayashi H, Takahashi K, Perrakis A, Weber K, Hohenberger W, Sugihara K, Quirke P. Understanding optimal colonic cancer surgery: comparison of Japanese D3 resection and European complete mesocolic excision with central vascular ligation. J Clin Oncol. 2012 May 20;30(15):1763-9. doi: 10.1200/JCO.2011.38.3992. Epub 2012 Apr 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival at 3 years	The length of time after surgery without any signs or symptoms of local or distant recurrence.	3 Years.
Secondary	Safety-Operative time.	Total time from incision to skin closure expressed in minutes.	Intraoperative
Secondary	Safety-Intraoperative blood loss.	Defined by the volume drained in cm2 into aspiration systems and weight of gauzes, calculated, subtracting the weight of the dry gauzes and volume of saline solution used for irrigation.	Intraoperative
Secondary	Safety-Intraoperative blood transfusion.	Defined as the number of red blood cells, platelets, or plasma units transfused during the intraoperative time.	Intraoperative
Secondary	Safety- Intraoperative Complications.	Defined as any deviation from the ideal intraoperative course occurring during the operative time, Using the Classi?cation of Intraoperative Complications(CLASSIC).	Intraoperative
Secondary	Early postoperative complications.	Number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification.	30 postoperative days.
Secondary	Late postoperative complications.	The number of patients with any deviation from the normal postoperative course grading by The Clavien-Dindo classification.	From the 31st postoperative days to the end of the study.
Secondary	Safety- Length of stay.	Defined as the length of an inpatient episode of care, calculated from the day of operation to the first discharge and based on the number of nights spent in the hospital.	30 Days.
Secondary	Safety- Postoperative mortality rate.	The all-cause death rate, within 30 days after surgery in or out of the hospital.	30 Days.
Secondary	Overall Survival at 3 years	Defined as the time from random assignment to the date of death due to any cause.	3 Years.
Secondary	Overall Survival at 5 years.	Defined as the time from random assignment to the date of death due to any cause.	5 Years.
Secondary	Disease-free survival.	Defined as the length of time after Surgical treatment (CME+CVL or Conventional non-CME procedure) that the patient survives without any signs or symptoms of colon cancer.	5 Years.
Secondary	Other Oncologic outcomes.	The number of positive, negative, and total lymph nodes harvested, Quality of surgery specimen, quality of life by EORTC specific Questionnaires	30 Days.