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Trial registered on ANZCTR


Registration number
ACTRN12621000199819
Ethics application status
Approved
Date submitted
22/12/2020
Date registered
25/02/2021
Date last updated
3/03/2022
Date data sharing statement initially provided
25/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Role of EMT (epithelial mesenchymal transition) in metastatic breast cancer: Association with eribulin and cyclin dependent kinase inhibitor treatment and disease recurrence
Scientific title
Role of EMT (epithelial mesenchymal transition) in metastatic breast cancer: Association with eribulin and cyclin dependent kinase inhibitor treatment and disease recurrence
Secondary ID [1] 303069 0
NA
Universal Trial Number (UTN)
U1111-1263-0433
Trial acronym
EMT Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 320139 0
Condition category
Condition code
Cancer 318081 318081 0 0
Breast

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
To assess if the presence of markers associated with EMT in the primary and metastatic breast cancer (BC) specimens predicts for a worse outcome in terms of metastatic recurrence in patients who have received chemotherapy in the adjuvant setting, and in patient’s clinical response to cyclin D kinase inhibitors and eribulin in the metastatic setting.
Data stored in the Principal Investigator's secure patient database will be used to identify eligible participants. Primary tissue samples will be obtained from previous surgeries and metastatic tissue from standard of care (SOC) biopsies. Both will be available in local laboratories.
A subset of eligible patients (prospective sub-type) who are currently receiving or are about to receive eribulin will be asked to consent to metastatic biopsy, or consent to use of SOC metastatic biopsy from prior to commencement of eribulin and at time of progression or cessation of treatment due to intolerability. There are no other requirements for patient to attend or participate actively in the study.
Medical records, including pathology and radiology reports, and data from the PI's secure database will be reviewed both prospectively both retrospectively to identify new BC events, as well as detail on duration of systemic treatment delivery, to categorise the basis on which disease progression was determined. This will be defined as (i) unequivocal clinical progression alone, (ii) unequivocal radiological evidence of disease progression and/or new disease, and (iii) combined clinical and radiological evidence leading to determination of disease progression.
Data is collected prospectively as to the significant site of disease progression leading to a change in systemic treatment, but greater detail will be obtained as to the site(s) of disease progression from reviewing clinical notes and radiological reports.
Data are already collected for the study apart from the prospective subset. These patients will not be asked to attend any study-specific visits after metastatic biopsy. The estimated time for these patients to be on standard of care treatment with eribulin is 2 to 5 years.
Intervention code [1] 319357 0
Early Detection / Screening
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 326068 0
Presence of biomarkers E cadherin, AE 1/3, Vimentin, N cadherin, Zeb 1, pSMAD2 and SMAD4 associated with EMT will be determined by immunoperoxidase staining by a single pathologist. Samples will be defined as negative if there is complete absence or </=1% staining. Samples scoring >1% will be defined as positive and will undergo tumour cell staining.
Timepoint [1] 326068 0
Pre-exisiting samples from primary diagnosis and at metastatic diagnosis will be received in batches from the laboratory and will be reviewed by the pathologist on an ongoing basis. The assessment is expected to be completed by March 2022.
Secondary outcome [1] 390016 0
Genomic alterations in Cadherin 1, KRT 18, Cadherin 2, Vimentin, Twist1, SNAIL1, SNAIL2, ZEB1 and ZEB2 will be assessed by ddPCR in a subset of patients where immunohistochemistry demonstrates changes in EMT expression.
Timepoint [1] 390016 0
Pre-exisiting samples from primary diagnosis and from metastatic diagnosis will be received in batches from the laboratory weekly and will be reviewed by the pathologist on an ongoing basis. Eligible samples will be batched and sent for genomic assessment on an ongoing basis. The assessment is expected to be completed by April 2022

Eligibility
Key inclusion criteria
a) Consent to use of tumour tissue
b) Histologically confirmed BC with archived primary BC tissue available
c) Diagnosis of metastatic BC where histological confirmation has been
confirmed in patient with de novo metastatic BC or histological/ cytological /
unequivocal radiologic diagnosis of metastatic disease in a patient with prior
diagnosis breast cancer
d) Patients with hormone receptor positive, HER2 negative BC who have (i)
received a cyclin D kinase inhibitor in the adjuvant setting and who has
experienced a BC recurrent event or (ii) received a cyclin D kinase inhibitor in
the metastatic setting
e) Any metastatic BC patient who has received at least one dose of eribulin in
the course of their metastatic BC
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Non-breast metastatic malignancy after BC diagnosis
b) Lost to follow-up (incomplete data in medical records and/or PI's secure database to provide adequate information)
c) Inadequate tumour tissue for biomarker analysis

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Associations between the presence of markers associated with EMT in the
specimens and metastatic recurrence will be assessed using Chi-squared tests for
patients who have received chemotherapy in the adjuvant setting, and in patient’s clinical response to cyclin D kinase inhibitors and eribulin in the metastatic setting.
Logistic regression will be performed to assess these associations while adjusting for
age and stage at BC diagnosis and the odds ratio and 95% CI will be reported.
Presence of markers associated with EMT in the primary tissue and its associations
with disease-free period, duration of response to systemic treatments and
survival/time to death will be analysed using Cox regression and plotted with Kaplain
Meier curves. Similarly, these tests will be performed on testing if molecular markers
associated with induction of EMT in metastatic lesions predicts for shorter posttreatment
overall survival. Associations between biomarkers (including expression of genes) and BC outcomes
(including recurrence, response to systemic treatment) will be assessed using Chisquared
tests. Logistic regressions will be performed to assess these associations
and the odds ratio and 95% CI will be reported.
Association between presence of markers associated with EMT and presence of
CNS disease will be assessed using Chi-squared test. Logistic regressions will be
performed to assess these associations and the odds ratio and 95% CI will be
reported.
Associations between presence of markers associated with EMT and expression of
PD-1 and PD-L1 will be assessed using Chi-squared tests. Logistic regressions will
be performed to assess these associations and the odds ratio and 95% CI will be
reported.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/04/2021
Actual
12/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
252
Accrual to date
126
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 18243 0
Breast Cancer Research Centre - Western Australia - Perth
Recruitment postcode(s) [1] 32307 0
6000 - Perth

Funding & Sponsors
Funding source category [1] 307476 0
Commercial sector/Industry
Name [1] 307476 0
Eisai Europe Limited
Country [1] 307476 0
United Kingdom
Primary sponsor type
Charities/Societies/Foundations
Name
Breast Cancer Research Centre - WA
Address
Suite 407, Hollywood Consulting Centre, 91 Monash Avenue, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 308148 0
None
Name [1] 308148 0
Address [1] 308148 0
Country [1] 308148 0
Other collaborator category [1] 281572 0
Individual
Name [1] 281572 0
Associate Professor Pieter Eichhorn
Address [1] 281572 0
School of Pharmacy and Biomedical Sciences,
Curtin Health Innovation Research Institute,
Curtin University, Kent St
Bentley, Western Australia 6102
Country [1] 281572 0
Australia
Other collaborator category [2] 281573 0
Individual
Name [2] 281573 0
Dr Jespal Gill
Address [2] 281573 0
PathWest Pathology, QEII Medical Centre J Block, Hospital Ave, Nedlands WA 6009
Country [2] 281573 0
Australia
Other collaborator category [3] 281574 0
Individual
Name [3] 281574 0
Dr HuiJun Chih
Address [3] 281574 0
School of Public Health, Curtin Health Research and Data Analytics Hub - WAHTN Clinical trials Data Centre, Faculty of Health Sciences, Curtin University, Kent St, Bentley, Western Australia 6102
Country [3] 281574 0
Australia
Other collaborator category [4] 281575 0
Individual
Name [4] 281575 0
Dr Nicola O'Neill
Address [4] 281575 0
BCRC-WA Suite 407, Level 4 Hollywood Consulting Centre, 91 Monash Ave, Nedlands, WA 6009
Country [4] 281575 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307552 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 307552 0
123 Glen Osmond Road
Eastwood
South Australia
5063
Ethics committee country [1] 307552 0
Australia
Date submitted for ethics approval [1] 307552 0
26/10/2020
Approval date [1] 307552 0
15/12/2020
Ethics approval number [1] 307552 0
2020-10-1034

Summary
Brief summary
The EMT study is investigating a molecular process (epithelial-mesenchymal transition) which can occur in the breast cancer cells of some patients, which can make the cancer more aggressive and might reflect how well the cancer cells will respond to treatment.

Who is it for?
Eligible patients in this study are aged 18 years or older, have been diagnosed with hormone receptor positive, HER2 negative breast cancer and have received a cyclin D kinase inhibitor in the adjuvant setting and have experienced a breast cancer recurrent event, or have received a cyclin D kinase inhibitor for treatment of metastatic cancer. Any metastatic breast cancer patient who has received at least one dose of eribulin in the course of their treatment may also be eligible.

Study details
All participants enrolled in this study will be asked to provide 1-2 tumour biopsies (tissue samples) that will be used to perform the molecular tests to determine EMT activity. Samples from previous surgeries and/or biopsies may be used to perform the molecular tests. Some eligible participants may be asked to undergo a maximum of two new biopsies if tissue from prior procedures is not available. No other patient procedures will be performed.

It is hoped this research will provide more information regarding the EMT process which may allow doctors to better select treatment for their patients whose breast cancer has this feature, and potentially allow the development of new drugs which can target the EMT process to increase cancer cell kill.
Trial website
Not applicable
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 107646 0
Prof Arlene Chan
Address 107646 0
Breast Cancer Research Centre of Western Australia
Suite 406, Hollywood Consulting Centre
91 Monash Avenue,
Nedlands WA 6009
Country 107646 0
Australia
Phone 107646 0
+61 8 9481 4522
Fax 107646 0
+61 8 9481 4544
Email 107646 0
[email protected]
Contact person for public queries
Name 107647 0
Nakita Stephens
Address 107647 0
Breast Cancer Research Centre of Western Australia
Suite 407, Hollywood Consulting Centre
91 Monash Avenue,
Nedlands WA 6009
Country 107647 0
Australia
Phone 107647 0
+61 8 6500 5560
Fax 107647 0
+61 8 6500 5599
Email 107647 0
[email protected]
Contact person for scientific queries
Name 107648 0
Arlene Chan
Address 107648 0
Breast Cancer Research Centre of Western Australia
Suite 406, Hollywood Consulting Centre
91 Monash Avenue,
Nedlands WA 6009
Country 107648 0
Australia
Phone 107648 0
+61 8 9481 4522
Fax 107648 0
+61 8 9481 4544
Email 107648 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.