UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000028995
Receipt number R000030875
Scientific Title Multicenter study to evaluate the extent of breast cancer through the use of contrast-enhanced ultrasound (CE-US).
Date of disclosure of the study information 2017/09/04
Last modified on 2021/02/06 15:05:25

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Basic information

Public title

Multicenter study to evaluate the extent of breast cancer through the use of contrast-enhanced ultrasound (CE-US).

Acronym

Evergreen Study

Scientific Title

Multicenter study to evaluate the extent of breast cancer through the use of contrast-enhanced ultrasound (CE-US).

Scientific Title:Acronym

Evergreen Study

Region

Japan


Condition

Condition

Operable breast cancer

Classification by specialty

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO


Objectives

Narrative objectives1

This is a multicenter retrospective study designed to evaluate the deficiency of the maximum diameter of the tumor between in the pathological investigation and in the B-mode of ultrasound and contrast enhanced ultrasound (CEUS) individually. Moreover, this is also designed to analyze the findings in the area detected in not B-mode but CEUS.

Basic objectives2

Bio-equivalence

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

The diameter obtained from the difference between the pathological investigation and the maximum diameter calculated using CEUS.

Key secondary outcomes

Secondary endpoint
1. The difference in mm between the tumor measured by CEUS and by pathological examination was obtained by measuring the difference between the pathological diameter and the maximum diameter calculated using B-mode.
2. The difference between the diameter found in B-mode compared to the pathological malignant diameter, and the difference in size between the diameter in CEUS measured against the pathological malignant diameter.
3. Pathological findings in the area where the lesion is detected by using CEUS rather than by B-mode.
4. Subgroup analysis for the difference between the pathological malignant diameter and B-mode/CEUS such as at the one-year post-diagnostic point, ER, HER2, lymphatic invasion and nuclear grade.
5. Analysis for the systemic error of length between CEUS/B-mode and pathological diameter.

Exploratory endpoint
1. The difference of the maximum diameter in mm between the tumor measured by accumulated images and that found in default images in CEUS.
2. Pathological status (invasive, non-invasive, normal variation) of the parts, which were able to be observed by CEUS, but not B-mode.


Base

Study type

Observational


Study design

Basic design


Randomization


Randomization unit


Blinding


Control


Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

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



Eligibility

Age-lower limit


Not applicable

Age-upper limit


Not applicable

Gender

Male and Female

Key inclusion criteria

1. Patients who had received breast surgery for breast cancer and whose diagnosois had been confirmed pathologically.
2. Pathological diagnosis was performed and tumor diameters data were available.
3. Pathological report included mapping of cancer sites.
4. Tumor diameter was measurable using B-mode and CEUS.
5. B-mode and CEUS were conducted in 3 months before breast surgery.
6. The maximum diameter was measured in approximately the same section for both B-mode and CEUS.
7. Perflubutane (Sonazoid) was used for CEUS.
8. Frozen flame and video images were both preserved in patient records.

Key exclusion criteria

1. Prior breast surgery and radiation therapy.
2. Prior systemic therapy including chemotherapy, hormone therapy, and molecular target therapy in 3 months before registration.

Target sample size

140


Research contact person

Name of lead principal investigator

1st name Hiroaki
Middle name
Last name Shima

Organization

Sapporo Medical University

Division name

Department of Surgery, Surgical Oncology and Science

Zip code

060-8543

Address

S 1, W 16, Chuo-ku, Sapporo, 060-8543, Japan

TEL

+81-11-611-2111

Email

simahiro@sapmed.ac.jp


Public contact

Name of contact person

1st name Hiroaki
Middle name
Last name Shima

Organization

Sapporo Medical University

Division name

Department of Surgery, Surgical Oncology and Science

Zip code

060-8543

Address

S 1, W 16, Chuo-ku, Sapporo, 060-8543, Japan

TEL

+81-11-611-2111

Homepage URL


Email

simahiro@sapmed.ac.jp


Sponsor or person

Institute

Department of Surgery, Surgical Oncology and Science, Sapporo Medical University

Institute

Department

Personal name



Funding Source

Organization

The Japan Association of Breast and Thyroid Sonology

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization



Other related organizations

Co-sponsor


Name of secondary funder(s)



IRB Contact (For public release)

Organization

IRB

Address

S1, W16, Chuo-ku, Sapporo

Tel

011-611-2111

Email

simahiro@sapmed.ac.jp


Secondary IDs

Secondary IDs

NO

Study ID_1


Org. issuing International ID_1


Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions



Other administrative information

Date of disclosure of the study information

2017 Year 09 Month 04 Day


Related information

URL releasing protocol

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000030875

Publication of results

Unpublished


Result

URL related to results and publications

https://doi.org/10.1007/s12282-020-01176-y

Number of participants that the trial has enrolled

152

Results

The mean widths as measured by the participating investigators were 15 +/- 7 mm (B-mode), 19 +/- 8 mm (CEUS), and 17+/-9 mm (P). The difference subtracted P from B-mode was - 3+/-7 mm (p<0.0001), and that from CEUS was 1+/-6 mm (p = 0.0163). The mean widths as measured by the independent reviewers were 16 +/- 7 mm (B-mode) and 18 +/- 7 mm (CEUS). The difference subtracted P from B-mode was - 2 +/- 8 mm (p = 0.0114), while that from CEUS was 1 +/- 7 mm (p = 0.1921).

Results date posted

2021 Year 02 Month 06 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

The patient eligibility criteria were as follows: breast surgery following a pathological diagnosis, complete data regarding tumor width and surgical specimen mapping including documentation and photos, B-mode and CEUS imaging performed prior to breast surgery, and similar probe angles between the B-mode and CEUS images and the direction of pathological excision.

Participant flow

The median period for registered in each institution was 19 months (1-38 months) between August 2012 and January 2017 at 10 institutions in Japan. 912 patients were screened who had received B-mode/CEUS and breast surgery with primary breast cancer. The most common recruiting issue was the criteria that only those patients be included who had had similar plane B-mode and CEUS, with corresponding pathological findings in the same direction. Accordingly, 759 patients were excluded, and only 153 were enrolled. After excluding one patient in whom the tumor diameter exceeded the width of the transducer, a final total of 152 patient data sets were analyzed.

Adverse events

None.

Outcome measures

The primary endpoint was a comparison of maximum tumor width measured by CEUS and that by P (CEUS-P). The secondary endpoint was a comparison of maximum tumor width measured by B-mode and that by P (B-mode-P). In an additional exploratory analysis, we investigated the presence of pathologically cancerous or non-cancerous lesions in areas that showed enhancement on CEUS (invisible in B-mode) but were not visualized outside the area of visible tumor on B-mode.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2017 Year 02 Month 10 Day

Date of IRB

2017 Year 02 Month 10 Day

Anticipated trial start date

2017 Year 06 Month 27 Day

Last follow-up date

2019 Year 03 Month 31 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information

This study is being conducted as a research group of Japan Association of Breast and Thyroid Sonology (JABTS).


Management information

Registered date

2017 Year 09 Month 04 Day

Last modified on

2021 Year 02 Month 06 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030875


Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name