Open D3 Right Hemicolectomy Compared to Laparoscopic CME for Right Sided Colon Cancer (D3/CME)

Open D3 Right Colectomy Compared to Laparoscopic CME Right Colectomy for Right Sided Colon Cancer; an Open Randomized Controlled Study

The primary focus in this study is to investigate and improve the surgical technique. In addition the collection of clinical data during diagnostic and follow up and the collection of tumor and blood gives us the opportunity to investigate tumor biology and its relevance in terms of determine appropriate treatment strategy both surgically and oncological and to assess and predict treatment outcome.

The aim of this study is to compare short and long-term outcomes between open D3 and laparoscopic CME (complete mesocolic excision) with CVL (central vascular ligation) right colectomy for right-sided colon cancer. Our primary hypothesis is that laparoscopic surgery improves quality of life by reducing pain, postoperative complications and thereby reduces hospital stay and convalescence. On the other hand it is to prove non-inferiority of the laparoscopic group compared to the open group by means of oncological outcome (survival, recurrence). Secondary aim is to evaluate surgical quality by comparing actual vascular stump length between the two groups by postoperative CT and compare number of lymph nodes removed with the specimen. With the use of liquid biopsy we want to detect circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) and evaluate their value as tumor markers by comparing the prognostic and predictive value. The hypothesis is that ctDNA and CTCs are more sensitive than standard parameters and imaging (CT CEA).

Study Overview

• Status: Recruiting
• Conditions: Quality of Life; Complication; Surgical Procedure, Unspecified; Circulating Tumor Cell; Lymph Node Metastases
• Intervention / Treatment: Procedure: Open surgery; Procedure: Right colectomy; Procedure: Central lymphadenectomy and vascular ligation; Procedure: Laparoscopic surgery

Detailed Description

This is a prospective, randomized, multi-center clinical study. The short term outcome, 2 and 5 year survival and mortality rates will be compared between the groups operated with open D3 resection at Haukeland University hospital and laparoscopic CME with CVL right hemicolectomy at Haraldsplass Deaconess hospital. Computer generated block randomization will be used.

All patients ≤ 85 years with tumor localized in the right colon will be considered to participate in the study. The patients will be summoned to the first consultation to the hospital they are referred to. They will be informed of the study. A patient who meets the inclusion criteria will be asked to participate in the study and sign the informed consent. A patient who accepts will be assigned a sequential participant number and then referred to open D3 or laparoscopic CME (right hemicolectomy) according to a pre-specified randomized list of treatments.

All patients referred with right sided colon cancer in the inclusion period will be registered, and the reason why some do not participate in the study will be documented. Patients who decline to participate in the study will be assigned standard treatment in the institution they are referred to.

Blood samples for analysis of ctDNA/CTCs will be collected preoperatively, 3-10th postoperative day, at 3 months and at each check the next five years at six months intervals. All sample times except the first postoperative control, correspond to the time of CEA and CT in ordinary follow-up. Proteomic technology based analysis of tumor tissue

• Study Type: Interventional
• Enrollment (Anticipated): 126
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristin B Lygre, M.D; Phone Number: 004755978500; Email: kristin.bentung.lygre@haraldsplass.no
• Study Contact Backup: Name: Frank Pfeffer, Ph.D; Phone Number: 004755975000; Email: frank.pfeffer@helse-bergen.no

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Recruiting
    • Haraldsplass
    • Contact: Kristin B Lygre, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• • Patients with malignant tumor of the right colon (cecum, ascending colon, right flexure and right transverse) at CT, colonoscopy.

  • Patients medically cleared by anesthesiologist for general anesthesia and oncological radical resection
  • Patients ≤ 85 years
  • Signed informed consent form

Exclusion Criteria:

• • Patients with recurrent cancer after previous surgery

  • Patients with synchronous distant metastasis
  • Patients with ongoing oncological treatment due to other cancer

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
Experimental: Open D3; Right colectomy Open surgery Central lymphadenectomy and vascular ligation	Procedure: Open surgery; Procedure: Right colectomy; Procedure: Central lymphadenectomy and vascular ligation
Active Comparator: Laparoscopic CME with CVL; Right colectomy Laparoscopic surgery Central lymphadenectomy and vascular ligation	Procedure: Right colectomy; Procedure: Central lymphadenectomy and vascular ligation; Procedure: Laparoscopic surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications	Surgical and general complications by Clavien-Dindo Classification og surgical complications	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical quality vascular resection	Vascular stump length in mm	6 months
Surgical quality lymph nodes	Number of lymph nodes	6 months
Patient outcome general	15D Health-related quality of life (HRQoL) preoperative and at 6 months. Scale 0-1. a higher score reflects a better HRQoL	6 months
Patient outcome bowel function	Quality of life (LARS (low anterior resection syndrome) score preoperative and at 6 months. Scale 0-42, where 0 reflects no LARS and 30-42 major LARS.	6 months
Oncological outcome survival	Survival in months	60 months
Oncological outcome recurrence	Time to recurrence in months	60 months
Prognostic significance of ctDNA	copies/mL plasma or % fractional abundance (mutant/total ctDNA)	60 months
Prognostic significance of CTCs	CTC/ml blood	60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the D3 specimen with the CME specimen morphologically	West classification	4 weeks
Operative parameters time	Operating time in minutes	1 day
Operative parameters blood loss	Intraoperative blood loss in ml	1 day
Operative parameters bleeding	Incidents of bleeding from central vascular structures; yes/no	1 day
Postoperative parameters	Incisional hernias; yes/no	6 months
Hospitalization	Total length of stay, including readmissions within 30 days	30 days

Collaborators and Investigators

• Sponsor: Haraldsplass Deaconess Hospital
• Collaborators: University of Bergen; Helse-Bergen HF
• Investigators: Study Director: Kristin B. Lygre, M.D, Haraldsplass Deaconess Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Anticipated): September 1, 2026
• Study Completion (Anticipated): September 1, 2026

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 13, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Complications; Colon cancer; Laparoscopy; D3 lymphadenectomy; Right-sided; Circulating tumor cells; Circulating DNA (cDNA); Complete mesocolic excision
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Lymphatic Metastasis; Colonic Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: REK 2015/2396

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No