Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06329102 |
| Other study ID # |
93628 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2021 |
| Est. completion date |
September 1, 2025 |
Study information
| Verified date |
March 2024 |
| Source |
Haukeland University Hospital |
| Contact |
Frank Pfefer, Prof |
| Phone |
48180021 |
| Email |
frank.pfeffer[@]helse-bergen.no |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Aim of the project is to surveil results after extended lymphadenectomy for right sided colon
resection for cancer with different operative techniques. Patients operated for right sided
colon cancer will be involved. There are different operative methods used in terms of extend
of lymphadenectomy and access (open, laparoscopic and robotic assisted) that are already
implemented. The Norwegian standard operation contains less extended lymph node dissection.
Patients operated by the standard method will serve as control group. Choice of access and
extend of lymph node dissection in Norway is dependant on the surgeon and hospital. At
Haukeland University Hospital extend and access of surgery are determined by a
multidisciplinary team meeting. More radical surgery might result in more complications and
the benefit for the patients in terms of oncological result and survival is uncertain. At
Haukeland University Hospital, extended lymphadenectomy has been mostly performed by open
surgery. During the study phase we will introduce extended lymphadenectomy by laparoscopy and
robotassisted surgery. Hypothesis is that more radical surgery performed by minimal invasive
surgery will result in equal or better oncological results, and less complications, shorter
hospital stay and better quality of life. As method we choose a prospective observational
study. All eligible patients with adenocarcinoma of the right colon without another ongoing
oncological treatment for other cancers will be included. Patientdata will be prospectively
registered in a web-based database. Aim of the study will be to define the optimal extend of
lymphadenectomy to achieve the best oncological result. In addition, we will analyse the
results dependent on the surgical access (open, laparoscopic or robotic). The assumed
difference between the operative methods is small. Therefore, the study is designed and
approved as a multicenter registration in order to achieve the necessary statistical power.
Description:
Right colectomy for colon cancer database
1. Scientific plan: 1.1. Rationale for the project Colon cancer is the third most cancer in
Norway. Five-year relative survival for men and women is 65% and 69% respectively. Surgery is
the cornerstone of the treatment and about 50% of patients are cured by surgery alone. In
2018, 2117 patients with stage I-III colon cancer were operated in Norway. About half of them
with right-sided colectomies. Parallel to the development of minimally invasive surgery,
focus on more radical surgical technique has been increasing, inspired by the improved
survival in rectal cancer. Despite growing interest in surgical technique, the level of
evidence in this area is low. Reasons are the lack of a common definitions of surgical
technique and anatomical differences between the right and left colon. There are two sets of
terms used to describe radical colon cancer surgery with adequate lymph node harvest and
dissection along embryological planes. The Japanese D2 and D3 dissection refers to lymph node
stations and the corresponding European "complete mesocolic excision" (CME) and central
vascular ligation (CVL) to anatomical planes. Despite the mentioned uncertainties, there is
growing evidence that more radical surgery is leading to improved oncological outcome in
right- sided colon cancer. Minimal invasive surgery improves quality of life by reducing
pain, postoperative complications and thereby reduces hospital stay and convalescence, but
there is concern that more radical surgery is associated with more intraoperative injuries
and severe non-surgical complications than "conventional" resection for colon cancer. Robotic
assisted right-sided colectomy could overcome the technical challenges of more radical
surgery with all benefits from minimal invasive surgery. Introduction of new health
technologies may cause serious harm to patients and has to be monitored carefully. In Norway,
reporting to the Norwegian Cancer Registry and the Norwegian Registry for Gastrointestinal
Surgery is mandatory. But both registries do not cover details of the surgical technique,
route of access and quality of the specimen.
1.2. Participating institutions and database solution To date, the applicants have several
databases approved by the local ethics committee that cover different topics of colorectal
cancer. In order to make the database accessible to a larger cohort we decided to create a
web-based solution. From the existing databases, a selection of a maximum of 50 parameters
have to be transferred.
The database will be designed as an easy to use, cloud-based solution which enables multiuser
and multicenter utility. The database will have filters and include tools for analysis and
statistics to facilitate generation of descriptive data to be used for data quality assurance
and hypotheses testing. This function will also provide regular reports (i.e. every 6 months)
to ensure data quality and patient safety during the introduction of more radical surgery and
throughout the study. The web-access functionality of the database went through a risk and
vulnerability analysis of the local health care authorities and is approved by "Helse Vest
IKT". It will also have the possibility to include patient outcome measures (PROMS) and
patient reported experience (PREMS) modules. In order to reach statistical power for some
hypothesis (i.e. oncological outcome) we will need a sample size that is too big for a single
institution. Therefore, the database will be offered to all Norwegian hospitals operating
right-sided colectomies.
1.3. Data collection To have a valid control group, all operations for right-sided colon
cancer will be registered, including open, laparoscopic and robotic assisted access. The
extend of surgery will be documented according to the Japanese D2 and D3 classification, as
D2-, complete D2- and D3 dissection. The quality of the specimen will be assessed by the
operating surgeon and pathologist by a newly proposed classification system for right-sided
colon cancer. Photo documentation of the anatomy after dissection will give the opportunity
to analyse the quality of surgery independently. All data will be recorded prospectively
immediately after the operation and after 30 days. Long-term outcomes such as survival,
hernia, and recurrences shall be checked 6 monthly. In addition, in order to avoid double
data entry oncological results will be collected from the Norwegian Cancer Registry and
postoperative complications from the Norwegian Registry for Gastrointestinal Surgery. Merging
data from national databases is current practice in Norway and there will be no delay.
Ethical committee has approved the study. The patients will be asked for informed consent
before data collection. Data can be collected in the web-based database Ledidi
(Intraoperative, postoperative form) or paper based. Participating other hospitals will get
access to the database after signing a collaboration and data processor agreement.
Health related quality of life (HRQoL) is assessed using the 15D instrument
(http://www.15d-instrument.net/15d), a validated, standardized, self-administered health
state descriptive questionnaire translated into Norwegian that can be used as a profile and
single index score measure.
1.4. Database and security: Ledidi Prjcts is a commercially available web-based software
solution developed, approved and used by the Oslo University Hospital (Rikshospitalet). The
database has been evaluated for risk and security (ROS) and is approved by the local IT
provider "Helse Vest IKT".
Ledidi's security system and Prjct's technical architecture are specified and implemented
according to requirements and templates from:
- "Normen" (Information security norm in the Norwegian health care sector)
- General Data Protection Regulation (GDPR)
- Health Insurance Portability and Accountability Act
- Strategy, which is the governing perspective
The developers are constantly working to ensure that the technical architecture and security
of the solution complies with the requirements referred to above. Ledidi's information
security governance consists of:
- Procedures, protection and technology, which constitute the implementing perspective
- Control, to handle nonconformities, among other things Procedures and technical
solutions ensure
1. data integrity and confidentiality, e.g. through a. encryption upon storage and b.
encryption during transport
2. authentication and authorization, implying that only the right people have the
right access
3. 2-factor authentication at login for further verification of user identity
4. directly identifiable data is only available to users with the correct access level
5. protection against denial of service attacks (DoS and DDoS) and other types of
attacks.
6. continuous logging and traceability
7. redundancy and scaling
8. deletion and return upon requests
9. secure storage management
10. backup and restore
1.5. Study Design This is a prospective comparative study, assessing complications and
oncological outcome following all types of colectomy procedures for right-sided colon cancer,
at the sponsor institution in the first instance. Open, laparoscopic and robotic assisted
operations will be included. Data from all patients undergoing the procedures will be
collected for at least 3 years in order to obtain information about eventual start of
adjuvant chemotherapy, incidence of hernia and oncological outcome (survival, recurrence).
Other institutions will be offered to collect their colectomy data in the Ledidi database for
free.
1.6. Aim of the study The primary aim of the project is to compare the impact of surgical
radicality on clinical outcomes for right-sided colon cancer. If sufficient sites participate
a large sample size could be achieved (see section 2.8), this will also enable statistical
comparison of oncological outcomes.
1.7. Study Endpoints Primary endpoint
- Surgical complications (Patient safety) Secondary endpoints
- Surgical quality (Specimen quality, number of lymph nodes)
- Quality of life after surgery
- Oncological outcome (survival, recurrence, adjuvant therapy) Surgical endpoints
- Operating time (min)
- Conversions
- Intraoperative blood loss/ perioperative transfusion units
- Significant incidents of bleeding from superior mesenteric artery, vein or their
branches in the mesentery requiring intervention
- Specimen quality
- Reoperations
- Anastomotic leak
- Prolonged postoperative ileus
- Total length of hospital stay/ readmissions within 30 days
- Incisional hernia at 6 months
1.8. Sample Size In Norway, about 1000 right-sided colectomies are performed annually and
about 60-80 scheduled, elective procedures at our institution. At present a randomization
between to different procedures with different radicality at a single institution will be
unethical if the more radical approach is already implemented. For that reason,
non-randomization will be the major bias. This could be overcome by multiple centers that
stick to detailed definitions of different procedures (D2, D3, complete D3) as mentioned
earlier. With a larger sample size, a propensity score in a case control study could be
performed. Another possibility will be to compare the results to historical or national data
from the registries.
An improvement from 40% complications (Clavian Dindo grade 2-5)14 to 20% in the robotic group
is considered statistically significant. To have a 90% power to detect such a difference a
sample size of 218 patients is needed. At our hospital about 60- 80 right-sided colectomies
were performed annually. Thus, the estimated total accrual period will be 3 years. Regarding
oncological results, to show a 10% improvement in 5 years relative survival between standard
lymph node dissection (D2) and extended dissection (D3) with a= 0,05 and power of 0,80 will
require 555 patients in each arm.
2. Ethical considerations All surgical techniques are used in clinical practice as
recommended and defined by national guidelines. But the distribution of access (open or
laparoscopic) and the extend of lymph node dissection varies between the different surgeons
and the Norwegian hospitals. At Haukeland University Hospital, open D3 dissection has been
performed since 2015 and is currently under evaluation by a randomized trial (REK Ref.nr.:
2015/2396: Open D3 right hemicolectomy compared to laparoscopic CME for right sided colon
cancer). The study results are published. Robotic assisted right-sided colectomy with
extended lymphadenectomy is performed since 2016. Laparoscopic right-sided colectomy is the
standard procedure. Since all operative techniques are implemented, the project should not
cause ethical problems. But at present, for operations outside a study protocol, the extend
of lymph node dissection for right-sided colectomies is not reported. Though a comparison
regarding the extend of lymphadenectomy is not possible.
