Study of Oncological Outcomes of D3 Lymph Node Dissection in Colon Cancer (COLD)

The purpose of this study is to determine wether D3 lymph node dissection gives superior oncological outcomes compared to standard D2 lymph node dissection in colon cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Colonic Neoplasms Malignant
• Intervention / Treatment: Procedure: Colonic resection with D2 lymph node dissection; Procedure: Colonic resection with D3 lymph node dissection

Detailed Description

The design involves random allocation of eligible patients to D3 or D2 lymph node dissection group in 1:1 ratio. The extent of colonic resection itself is not influenced by the randomization and is predefined by the investigator prior to randomization.

Requirements applied to centers participating in the trial and surgeons performing procedures are described in the protocol and refer to center volume and surgeon's experience with evaluation of non-edited video-recordings of procedures.

Routine quality control includes requirement to photograph vessels with the clip to determine the extent of lymph node dissection performed and a thorough morphological assessment of the specimen.

After surgery patients are treated according to local standards with no difference wether D2 or D3 lymph node dissection was performed. Short-term and long-term outcomes are registered as per protocol.

This is a superiority trial evaluating statistical superiority. With the 50% five year survival according to national registry for colon cancer, expecting 10% improvement in survival with D3 lymph node dissection, enrollment of 768 patients during 3 year accrual period followed by 5 year follow up is required for a power of 80%.

The intent-to-treat principle is used for the data analysis.

• Study Type: Interventional
• Enrollment (Actual): 780
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Russian Federation
  • Krasnodar, Russian Federation, 350000
    • Krasnodar City clinical hospital #1
  • Moscow, Russian Federation, 123423
    • State Scientific Centre of Coloproctology
  • Moscow, Russian Federation, 125130
    • Moscow city oncological hospital #62
  • Moscow, Russian Federation, 125284
    • P. Herzen Moscow Oncology Research Institute
  • Obninsk, Russian Federation, 450054
    • Medical radiological scientific center named after A.F. Tsyba
  • Rostov, Russian Federation, 344037
    • Rostov Research Institute of Oncology
  • Saint Petersburg, Russian Federation, 197022
    • St Petersburg City Clinical Oncology Dispensary
  • Saint Petersburg, Russian Federation, 197758
    • Saint-Petersburg Clinical Research center of specialized kinds of medical care (Oncology)
  • Saint Petersburg, Russian Federation, 197758
    • Scientific-Research institute of Oncology named after N.N. Petrov
  • Saint Petersburg, Russian Federation, 198103
    • Saint-Petersburg State University Clinic
  • Saint-Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • Ufa, Russian Federation, 450054
    • Republican clinical oncological dispencery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histologically confirmed adenocarcinoma of the colon (caecum, ascending, transverse, descending, sigmoid)
• clinical stage T1-4aN0-2M0-1 (distant metastases must be resectable)
• indications for surgical colonic resection
• ECOG status 0-2
• At least 18 years of age
• Written informed consent

Exclusion Criteria:

• Medical or psychiatric conditions that compromise the patient's ability to give informed consent or comply with the study protocol
• Pregnancy or breast feeding
• Medical contraindications for surgical treatment
• Synchronous or metachronous malignancy
• Non-resectable distant metastases
• Colon obstruction, perforation or bleeding complicating the tumor
• Indications for isolated transverse colon resection
• Neoadjuvant chemotherapy

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: D2 lymph node dissection; Colonic resection with D2 lymph node dissection	Procedure: Colonic resection with D2 lymph node dissection; Appropriate to the tumor location colonic resection is performed with D2 lymph node dissection
Experimental: D3 lymph node dissection; Colonic resection with D3 lymph node dissection	Procedure: Colonic resection with D3 lymph node dissection; Appropriate to the tumor location colonic resection is performed with D3 lymph node dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	overall survival of patients	5 years after last patient enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Survival without local or systemic recurrence	5 years after last patient enrolled
Postoperative morbidity	Complications after surgery	within the first 30 days after surgery
Postoperative mortality	Death after surgery	within the first 30 days after surgery
Postoperative recovery parameters	Complex of parameters describing the pattern of recovery after surgery (i.e. food tolerance, peristalsis, walking etc.)	within the first 30 days after surgery
Pattern of lymph node metastasis based on pathology report	Number of lymph node with metastases related to number of lymph nodes studied in each group in the specimen	enrollment period
CME quality	Ratio of good, satisfactory and unsatisfactory quality according to pathology report	enrollment period
Lymph node yield	Number of lymph nodes removed according to pathology report	enrollment period
Quality of life in patients after D2 and D3 lymph node dissection using questionnaire	CR29 and CR30 questionnaires by European Organization for Research and Treatment of Cancer	enrollment period

Collaborators and Investigators

• Sponsor: N.N. Petrov National Medical Research Center of Oncology
• Investigators: Study Chair: Aleksei Karachun, Ph.D., N.N. Petrov Research Institute of Oncology, Surgical department of abdominal oncology, St. Petersburg, Russian Federation

Publications and helpful links

General Publications

• Karachun A, Petrov A, Panaiotti L, Voschinin Y, Ovchinnikova T. Protocol for a multicentre randomized clinical trial comparing oncological outcomes of D2 versus D3 lymph node dissection in colonic cancer (COLD trial). BJS Open. 2019 Mar 14;3(3):288-298. doi: 10.1002/bjs5.50142. eCollection 2019 Jun.
• Karachun A, Panaiotti L, Chernikovskiy I, Achkasov S, Gevorkyan Y, Savanovich N, Sharygin G, Markushin L, Sushkov O, Aleshin D, Shakhmatov D, Nazarov I, Muratov I, Maynovskaya O, Olkina A, Lankov T, Ovchinnikova T, Kharagezov D, Kaymakchi D, Milakin A, Petrov A. Short-term outcomes of a multicentre randomized clinical trial comparing D2 versus D3 lymph node dissection for colonic cancer (COLD trial). Br J Surg. 2020 Apr;107(5):499-508. doi: 10.1002/bjs.11387. Epub 2019 Dec 24.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2017
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: December 29, 2016
• First Submitted That Met QC Criteria: December 30, 2016
• First Posted (Estimate): January 4, 2017

Study Record Updates

• Last Update Posted (Actual): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: colon cancer; lymph node dissection; D3 lymph node dissection
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: COL-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We are not planning to share personal patient data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No