The OMEGA trial will primarily investigate if omentum preservation (partial omentectomy) during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of three-year overall survival.
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Overall survival at three-years after the operation, defined as the period of
time between operation and death from any cause. Patients alive at last
follow-up are censored.
Secondary outcome
• Operating time
• Intraoperative blood loss
• Intraoperative complications
• Postoperative complications, defined according to the Clavien-Dindo
classification25 and comprehensive complication index (CCI)
• Late intra-abdominal complications, defined as complications related to the
initial operation, occurring between >30 days and five years after surgery
• Distribution of lymph node metastases
• R0 resection rate, defined as the percentage of patients who underwent a
microscopically complete (R0) resection
• Rate of malignant cells in cytology
• Serum CRP levels at postoperative days 3, 5 and 7
• Molecular classification of gastric cancer
• ICG fluorescent enhancement of omentum after resection, in omentum
preservation group only (in centers that have ICG fluorescence available)
• Protocol compliance to allocated treatment
• Escalation of care
• Hospital stay, defined as time interval between date of surgery and date of
hospital discharge
• Intensive care length of stay
• Readmission rate within 30-days after surgery
• Reintervention rate within 30-days after surgery
• Reoperation rate within three years after surgery
• Quality of life at baseline, 3, 6, 9, 12, 18 and 24 months, the following
questionnaires will be used: EQ-5D-5L, QLQ-C30, and QLQ-OG25
• 3- & 5-year disease-free survival, defined as the period of time from
operation to locoregional recurrence, peritoneal recurrence, distant
metastases, second gastric cancer or death from any cause. Patients alive and
free of all these events will be censored at the last follow-up
• 5-year overall survival, defined as the period of time from operation to
death from any cause. Patients alive and free of all these events will be
censored at the last follow-up
• Cost-effectiveness
Background summary
Gastric cancer is the fifth most prevalent type of cancer worldwide and the
third most common cause of cancer-related death. Overall, survival has improved
in recent decades with the introduction of perioperative chemotherapy; but as
yet, a radical gastrectomy remains the foundation of curative treatment for
advanced gastric cancer. An oncological resection involves a radical (R0)
gastrectomy with a modified D2 lymphadenectomy. Generally, a complete resection
of the greater omentum is also performed, with the hypothesis that the omentum
cold contain micrometastatic disease.
The necessity of complete omentectomy in gastrectomy for locally advanced
cancer is still unclear world-wide. This issue is currently also reflected by
various clinical practice guidelines. At present, the Japanese gastric cancer
guideline recommends a total omentectomy for clinically staged T3-T4 gastric
tumors, and partial omentectomy for T1-T2 tumors. Likewise, the National
Comprehensive Cancer Network (NCCN) Guidelines advises a total omentectomy
during resection with curative intent. Meanwhile, the European Society for
Medical Oncology (ESMO) guidelines makes no statement about the necessity of
omentectomy in the treatment of gastric cancer and the Dutch gastric cancer
guideline advises to perform at least a partial omentectomy.
The omentum contributes to the defense against infections, by functioning as
regulator of regional immune responses(6-9). Furthermore, the omentum prevents
the occurrence of adhesions that can lead to small bowel obstruction. In
(laparoscopic) gastric cancer surgery, omentectomy can be a time-consuming and
technically demanding procedure which has been shown to increase the risk of
intraoperative injuries to the colon and mesocolon, and additionally is
associated with an increased risk of postoperative complications following
various types of surgery, including gastric cancer surgery.
Also, there is little evidence supporting a survival benefit of routine
complete omentectomy in gastrectomy for cancer. Several non-randomized studies
have shown no survival difference between partial and complete omentectomy as
part of radical gastrectomy for gastric cancer. A recent systematic review
pooled the results of these studies and found that patients who underwent
partial omentectomy had a statistically higher 3-year and 5-year overall
survival rate than those who underwent total omentectomy. These studies suggest
that a total omentectomy can be omitted as part of potential curative surgery.
Therefore, preservation of the omentum could reduce early and late morbidity
and mortality, reduce operation time and readmissions resulting in improved
cost-effectiveness and improved quality of life for patients after gastrectomy
for cancer
Currently, two phase III trial are conducted in Japan and China (NCT04843215).
The aim of both trials is to confirm the non-inferiority of omentum
preservation compared with omentectomy. However, both trials exclude patients
receiving neoadjuvant chemotherapy, and patients undergoing minimally invasive
gastrectomy are excluded as well in the Japanese trial. Also, most of the
retrospective studies were performed in Asian countries, where gastric cancer
is more prevalent and more patients are diagnosed with early gastric cancer as
a consequence of screening. Hence, the results from Asian studies cannot
directly be applied to the Western world.
To date, the influence of omentectomy on survival has not yet been investigated
in a randomized controlled trial in a Western gastric cancer population. Our
preliminary study showed that the incidence of metastases in the greater
omentum is low, and when present, is associated with advanced disease and a
non-radical resection. With a median survival of 7 months, none of these
patients survived more than two years (submitted).
In this randomized controlled trial, we test our hypothesis that omentum
preservation during gastrectomy in patients with locally advanced gastric
cancer is non-inferior to complete omentectomy in terms of three-year overall
survival. The OMEGA trial will be the first Western randomized controlled trial
that will determine if complete omentectomy during gastrectomy for cancer can
be omitted in the future, potentially reducing overtreatment and thereby
increasing quality of life and decreasing medical costs.
Study objective
The OMEGA trial will primarily investigate if omentum preservation (partial
omentectomy) during gastrectomy for gastric cancer is non-inferior to complete
omentectomy in terms of three-year overall survival.
Study design
OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter
trial. Eligible patients have to be operable (ASA <4) with resectable
(*cT4aN3bM0) gastric cancer. Patients will be randomized in a 1:1 ratio between
radical (sub)total gastrectomy with omentum preservation or complete
omentectomy. Patients will be stratified according to center, neoadjuvant
therapy and type of surgery (total or subtotal gastrectomy). The primary
endpoint is overall survival at three-years after the operation. In total, 654
patients will be randomized.
The study will be conducted in five Dutch university hospitals, nine Dutch
teaching hospital and multiple international university hospitals, all
performing more than 20 gastrectomies annually.
Intervention
In this study, preservation of the omentum distal to the gastroepiploic vessels
will be compared with complete omentectomy during gastrectomy for cancer.
Study burden and risks
Theoratically, by not performing an omentectomy tumor cells could remain in the
body. However, previous studies have never concluded that omentectomy
contributes to a survival benefit. In addition, at six different times patients
are asked to complete a questionnaire about quality of life. These will all be
taken during the check-up appointments at the outpatient clinic so that the
burden on the patient remains minimal. Furthermore, blood samples will be taken
on days 3, 5 and 7 postoperatively. In almost all cases, in practice, blood is
already drawn from patients postoperatively on days 3, 5 and 7. As a result,
the burden here will be very small.
As a rule, the entire omentum is also removed during a gastric resection. The
idea behind this is that metastases are removed. However, there are also
disadvantages to performing a complete omentectomie. It is a technically
challenging part of the surgery that is time consuming and can lead to
complications such as damage to the colon and its blood supply, especially in
today's widely used minimally invasive surgeries. The average duration of a
complete omentum removal is over one hour. In addition, the omentum plays an
important role in fighting bacterial infections in the abdominal cavity and
preventing adhesions in the abdomen. Studies have shown that complete omentum
removal is an important risk factor for the development of adhesions and
associated complications, such as ileus (small bowel obstruction). Smaller
retrospective studies suggest that complete omentum removal during gastric
resection does not improve survival. A recently published systematic review
even suggests that patients may have a survival advantage with an
omentum-sparing gastrectomy (2). However, most of these studies have been
conducted in Asian countries, where gastric cancer is more common and more
patients are diagnosed with early gastric cancer as a result of screening.
It is expected that partial omentum removal during gastric resection is
non-inferior to surgery with complete omentum removal; that is, sparing the
omentum will not negatively affect 3-year survival. In addition, partial
omentectomy is expected to lead to better outcomes in terms of operative time,
complications (short and long term), quality of life and cost-effectiveness.
This means that it is reasonably plausible that the interest to be served with
the research is in proportion to the objections and the risk for the study
participants, and the conduct of the research is therefore justified in the
assessment of the OMEGA trial study group.
2.Zizzo, M., Zanelli, M., Sanguedolce, F., Palicelli, A., Ascani, S., Morini,
A., Tumiati, D., Mereu, F., Zuliani, A. L., Nardecchia, M., Gatto, F., Zanni,
M., and Giunta, A. (2022) Gastrectomy with or without Complete Omentectomy for
Advanced Gastric Cancer: A Meta-Analysis. Medicina 58, 1241
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- Primary resectable gastric adenocarcinoma, clinical stage T1-4aN0-3M0
- ASA 1-3 (able to undergo surgery)
- Scheduled for open or minimally invasive (sub)total gastrectomy with modified
D2-lymphadenectomy, with or without perioperative chemotherapy
- Age above 18 year
- Able to complete questionnaires in Dutch, English or Italian
- Written informed consent
- Esophageal invasion < 2 cm defined from the upper margin of the gastric rugae
as determined by endoscopy
Exclusion criteria
- Gastric cancer clinically staged as T1N0
- Locally advanced gastric cancer requiring multi-visceral resection
- Pregnancy
- Previous malignancy (excluding non-melanoma skin cancer, pancreatic
neuroendocrine tumor (pNET) <2cm, and gastrointestinal stromal tumor (GIST)
<2cm), unless no evidence of disease and diagnosed more than three years before
diagnosis of gastric cancer, or with a life expectancy of more than five years
from date of inclusion
- Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator
- Previous gastric or omental surgery, with the exclusion of a gastric
perforation
- Indication for thoracotomy/thoracoscopy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05180864 |
| CCMO | NL80328.029.22 |