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Trial registered on ANZCTR


Registration number
ACTRN12618001561279
Ethics application status
Approved
Date submitted
11/09/2018
Date registered
18/09/2018
Date last updated
9/02/2023
Date data sharing statement initially provided
9/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label, pharmacodynamic Study of (Z)-endoxifen in Patients with
Invasive Breast Cancer Prior to Undergoing Mastectomy or Lumpectomy.
Scientific title
An open label, pharmacodynamic Study of (Z)-endoxifen in Patients with
Invasive Breast Cancer Prior to Undergoing Mastectomy or Lumpectomy.
Secondary ID [1] 295819 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 309256 0
Condition category
Condition code
Cancer 308130 308130 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
- the dose administered, (Z)-Endoxifen 4 mg/day
- the duration of administration, a minimum of 21 days until the day before surgery, inclusive
- the mode of administration, oral capsules
A study diary will be provided to each participant for the purpose of recording study drug
administration (date and time) and adverse events.
A safety follow up phone call will be conducted on Days 7, 14, 21 and weekly thereafter until the visit before surgery. For each phone call the following will be performed:
- Document telephone contact day and time;
- Instruct the participant to volunteer any information regarding AEs that she may have experienced by asking an open question (e.g., “How do you feel?”).

Patient engagement in this study will be for a minimum of 43 days. This includes up to 28 days of screening period, treatment for at least 14-days and for no more than 30 days until the day before their scheduled surgery.
Intervention code [1] 312146 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 307110 0
To assess the effect of pre-operative oral (Z)-Endoxifen treatment on clinical response measured by Ki67 expression levels. Ki67 will be assessed via tumor biopsy analysis.
Timepoint [1] 307110 0
-pre-treatment - after treatment of a minimum of 14 and no more than 30 days.
Secondary outcome [1] 350706 0
Assess the effect of pre-operative (Z)-Endoxifen treatment on the expression levels of Estrogen Receptor (ER). ER will be assessed via tumor biopsy analysis.
Timepoint [1] 350706 0
- pre-treatment - after treatment of a minimum of 14 to 30 days.
Secondary outcome [2] 350709 0
Evaluate the safety and tolerability of (Z)-Endoxifen in breast cancer patients administered at 4 mg/day for a minimum of 14 days and no more than 30 days. The endpoint evaluations will include the following: - incidence and severity of adverse events; - vital signs parameters; - physical exam findings; - electrocardiogram parameters; - clinical laboratory parameters (serum chemistry, hematology, coagulation, urinalysis)
Timepoint [2] 350709 0
- Clinical visit on Day before Surgery - Follow up phone call on Day 7, and Day 15 and weekly until the day before surgery.
Secondary outcome [3] 350715 0
The study may assess the effect of pre-operative (Z)-Endoxifen treatment on the following markers: PCNA (S phase) via tumor biopsy analysis.
Timepoint [3] 350715 0
Secondary time point, update: Protocol amendment Change pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [4] 350717 0
The study may identify tumor RNA expression changes using RNA sequencing.
Timepoint [4] 350717 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [5] 351981 0
Assess the effect of pre-operative (Z)-Endoxifen treatment on the expression levels of Progesterone Receptor (PR). PR will be assessed via tumor biopsy analysis.
Timepoint [5] 351981 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [6] 351982 0
The study may assess the effect of pre-operative (Z)-Endoxifen treatment on the following markers: phospho-Histone H3 (M phase) via tumor biopsy analysis.
Timepoint [6] 351982 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [7] 351983 0
The study may assess the effect of pre-operative (Z)-Endoxifen treatment on the following markers: P16 and P21 (senescence) via tumor biopsy analysis.
Timepoint [7] 351983 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [8] 351984 0
The study may assess the effect of pre-operative (Z)-Endoxifen treatment on the following markers: Beta-Galactosidase (senescence) via tumor biopsy analysis.
Timepoint [8] 351984 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [9] 351985 0
The study may assess the effect of pre-operative (Z)-Endoxifen treatment on the following markers: TUNEL (apoptosis) via tumor biopsy analysis.
Timepoint [9] 351985 0
- pre-treatment - after treatment of a minimum of 14 to 30 days (changed from 21 days).
Secondary outcome [10] 418367 0
Correlate expression changes in Ki-67, ER and PgR to (Z)-Endoxifen blood concentration.
Timepoint [10] 418367 0
-pre-treatment - after treatment of a minimum of 14 to 30 days.

Eligibility
Key inclusion criteria
1.Females 18 years of age or older;
2. Histologically confirmed invasive breast cancer (stage 1 or 2, ER+ low- grade [grade 1 or 2]);
3. Pathological invasive breast cancer diagnosis requiring mastectomy or lumpectomy;
4. Newly diagnosed, tamoxifen naïve;
5. Scheduled to undergo mastectomy or lumpectomy for invasive breast cancer at no less
than 15 days from commencement of treatment with the study drug;
6. Estrogen Receptor positive biopsy, as determined from a biopsy specimen obtained no
more than 3 months prior to entry (>=1% of the cells by IHC);
7. HER2 negative (as determined by IHC and/or FISH from a biopsy specimen obtained no more than 3 months prior to entry;
8. Eastern Cooperative Oncology Group (ECOG) score 0-1, an estimated life expectancy of
at least 12 months;
9. Adequate organ function
10. Women with child-bearing potential must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study;
11. Provide consent for the collection of biopsy material;
12. Able to comprehend and sign the informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Diagnosis of inflammatory breast carcinoma;
2. Stage IV breast cancer;
3. Diagnosis of HER2 positive disease;
4. Palpable nodes or clinical suspicion of axillary node positivity;
5. Concurrent treatment with another anti-estrogen;
6. Presence of an infection including ulcerations and fungal infections in the breast to be studied;
7. Coagulopathies, bleeding diatheses, thrombocytopenia or current anticoagulant use;
8. Several hepatic impairments, defined as Child-Pugh Class C or worse;
9. Prior radiation to the breast or chest wall;
10. Known severe hypersensitivity to any drugs in this study;
11. Pregnant or lactating;
12. Impaired renal function;
13. Impaired cardiac function or history of cardiac problems;
14. Poor nutritional state (as determined by clinician);
15. Depressed bone marrow;
16. Presence of serious infection;
17. Presence of ascites (as determined by clinician);
18. Presence of pleural effusion;
19. Hepatic disease, positive serology (for hepatitis B surface antigen [HBsAg], hepatitis C virus [HCV] antibodies) or known active disease due to hepatitis B virus, hepatitis C virus, auto-immune liver disease or sclerosing cholangitis;
20. Positive serology for human immunodeficiency virus (HIV) or known active disease due to HIV infection;
21. Major operation, obvious trauma within 28 days before randomization;
22. Concurrent participation in an experimental drug study;
23. Any reasons for which the investigator considers the volunteer is not suitable for the study.
24. Concurrent chemotherapy.
25. History of previous thromboembolic events.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data analysis is complete
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
After review of initial data generated from the study, the decision was made to stop enrollment after completion of 7 subjects and progress to the next planned study due to positive outcomes observed.
Date of first participant enrolment
Anticipated
1/10/2018
Actual
12/10/2018
Date of last participant enrolment
Anticipated
Actual
30/11/2022
Date of last data collection
Anticipated
Actual
30/12/2022
Sample size
Target
25
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300413 0
Commercial sector/Industry
Name [1] 300413 0
Atossa Genetics AUS Pty Ltd, Australian entity of Atossa Therapeutics Inc
Country [1] 300413 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Atossa Genetics AUS Pty Ltd, Australian entity of Atossa Therapeutics Inc
Address
Level 16, Tower 2 Darling Park,
201 Sussex Street, Sydney NSW 2000
Australia.
Country
Australia
Secondary sponsor category [1] 299873 0
Commercial sector/Industry
Name [1] 299873 0
Avance Clinical Pty Ltd
Address [1] 299873 0
Level 1, 2 Ann Nelson Drive, Thebarton SA 5031, Australia
Country [1] 299873 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301218 0
Bellberry Human Research Ethics Committee E [EC00450]
Ethics committee address [1] 301218 0
Ethics committee country [1] 301218 0
Australia
Date submitted for ethics approval [1] 301218 0
16/05/2018
Approval date [1] 301218 0
11/07/2018
Ethics approval number [1] 301218 0
2018-05-355

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 86266 0
Dr Vinod Ganju
Address 86266 0
Peninsula and Southeast Oncology
Suite 7, Level 3, North Building
Frankston Private Hospital
5 Susono Way
FRANKSTON VIC 3199
Country 86266 0
Australia
Phone 86266 0
+61 3 9781 5244
Fax 86266 0
Email 86266 0
vg@paso.com.au
Contact person for public queries
Name 86267 0
Heather Fraser
Address 86267 0
Atossa Therapeutics INC. 107 Spring St Seattle, WA 98104 USA
Country 86267 0
United States of America
Phone 86267 0
+1 206 348 1804
Fax 86267 0
Email 86267 0
heather.fraser@atossainc.com
Contact person for scientific queries
Name 86268 0
Heather Fraser
Address 86268 0
Atossa Therapeutics INC. 107 Spring St Seattle, WA 98104 USA
Country 86268 0
United States of America
Phone 86268 0
+1 206 348 1804
Fax 86268 0
Email 86268 0
heather.fraser@atossainc.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The individual participant clinical trial data and metadata arising from this study are considered confidential, commercial trade secret information which is subject to subsequent product development and potential patent filings relating to the formulation of the investigational product.


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.