UMIN-CTR Clinical Trial

Public title

Surveillance for early gastric cancer after endoscopic submucosal dissection and H.pylori eradication.

Acronym

Surveillance for early gastric cancer after endoscopic submucosal dissection.

Scientific Title

Surveillance for early gastric cancer after endoscopic submucosal dissection and H.pylori eradication.

Scientific Title:Acronym

Surveillance for early gastric cancer after endoscopic submucosal dissection.

Region

Japan

Condition

Early gastric cancer

Classification by specialty

Gastroenterology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

The aim of this study is to elucidate the molecular mechanism of gastric carcinogenesis and develop the new therapeutic approach of gastric cancer.

Basic objectives2

Bio-equivalence

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Recurrence of gastric cancer after endoscopic submucosal dissection and Aberrant DNA methylation and aberrant expression of microRNAs, DNA, and proteins, including CD44v9, CagA and stemness-related factors, in gastric tumors and in background gastric mucosa such as atrophic and metaplastic mucosa

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Patients who were diagnosed as early gastric cancer and are considered as the indication of endoscopic submucosal dissection.

Key exclusion criteria

Patients who have anticoagulant therapy.
Patients who had total gastrectomy during the course observation.
Patients who do not respond to 2nd eradication thrapy of H.pylori.

Target sample size

100

Name of lead principal investigator

1st name
Middle name
Last name	Hidekazu Suzuki

Organization

Keio University, School of Medicine

Division name

Division of Gastroenterology and Hepatology

Zip code

Address

35 Shinanomachi, Shinjuku-ku, Tokyo

TEL

03-5363-3914

Email

hsuzuki@a6.keio.jp

Name of contact person

1st name
Middle name
Last name	Hidekazu Suzuki

Organization

Keio University, School of Medicine

Division name

Division of Gastroenterology and Hepatology

Zip code

Address

35 Shinanomachi, Shinjuku-ku, Tokyo

TEL

03-5363-3914

Homepage URL

Email

hsuzuki@a6.keio.jp

Institute

Keio University, School of Medicine

Institute

Department

Personal name

Organization

Division of Gastroenterology and Hepatology, Keio University, School of Medicine

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2008

Year

02

Month

27

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

http://www.nature.com/bjc/journal/v109/n2/full/bjc2013314a.html

Number of participants that the trial has enrolled

Results

BACKGROUND:
Multiple early gastric cancers (EGCs) may develop in 6-14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence.

METHODS:
Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed.

RESULTS:
The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71-83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30-18.8).

CONCLUSION:
CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2008

Year

02

Month

04

Day

Date of IRB

Anticipated trial start date

2008

Year

02

Month

01

Day

Last follow-up date

2016

Year

11

Month

30

Day

Date of closure to data entry

2017

Year

01

Month

31

Day

Date trial data considered complete

2017

Year

03

Month

31

Day

Date analysis concluded

2017

Year

03

Month

31

Day

Other related information

Recurrence of gastric cancer after endoscopic submucosal dissection
Aberrant DNA methylation and aberrant expression of microRNAs and proteins, including CD44v9 and CagA, in gastric tumors and epithelial tissues

MicroRNAs (miRNAs) are small noncoding RNAs that function as endogenous silencers of target genes and play critical roles during carcinogenesis. The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib has been highlighted as a potential drug for treatment of gastrointestinal tumors. The aim of this study was to investigate the role of miRNAs in gastric carcinogenesis and the feasibility of a new therapeutic approach for gastric cancer. miRNA expression profiles were examined in 53 gastric tumors including gastric adenomas (atypical epithelia), early gastric cancers and advanced gastric cancers and in gastric cancer cells treated with celecoxib. miRNA microarray analysis revealed that miR-29c was significantly downregulated in gastric cancer tissues relative to nontumor gastric mucosae. miR-29c was significantly activated by celecoxib in gastric cancer cells. Downregulation of miR-29c was associated with progression of gastric cancer and was more prominent in advanced gastric cancers than in gastric adenomas and early gastric cancer. In addition, expression of the oncogene Mcl-1, a target of miR-29c, was significantly increased in gastric cancer tissues relative to nontumor gastric mucosae. Activation of miR-29c by celecoxib induced suppression of Mcl-1 and apoptosis in gastric cancer cells. These results suggest that downregulation of the tumor suppressor miR-29c plays critical roles in the progression of gastric cancer. Selective COX-2 inhibitors may have clinical promise for the treatment of gastric cancer via restoration of miR-29c.

Registered date

2008

Year

02

Month

27

Day

Last modified on

2015

Year

09

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001271