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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
9/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
An open label, pilot and expansion pharmacodynamic Study of (Z)-endoxifen in Patients with Invasive Breast Cancer Prior to Undergoing Mastectomy or Lumpectomy.
Scientific title
An open label, pilot and expansion 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 50 days. This
includes up to 28 days of screening period, a minimum of 21 days treatment and the day of 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 21 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 21 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 21 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, 14 and D21, and weekly phone call post Day 21 to 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
- pre-treatment
- after treatment of a minimum of 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 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 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 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 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 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 21 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);
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 22 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 (by IHC and/or FISH);
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
Gender
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 or known active disease due to hepatitis B virus,
hepatitis C virus, auto-immune liver disease or sclerosing cholangitis;
20. Positive serology or known active disease due to HIV infection;
21. Major operation, obvious trauma within 28 days before study enrollment;
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 thromboembolitic 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
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300413 0
Commercial sector/Industry
Name [1] 300413 0
Atossa Genetics Inc.
Address [1] 300413 0
107 Spring St
Seattle, WA 98104
USA
Country [1] 300413 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Atossa Genetics Inc.
Address
107 Spring St Seattle, WA 98104 USA
Country
United States of America
Secondary sponsor category [1] 299873 0
Commercial sector/Industry
Name [1] 299873 0
CPR Pharma Services Pty Ltd
Address [1] 299873 0
Ground Floor
28 Dalgleish Street
THEBARTON SA 5031
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
129 Glen Osmond Rd
Eastwood SA 5063
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
The purpose of this study is to examine the action of a new medication (called “(Z)-endoxifen”) in patients with breast cancer.

Who is it for?
You may be eligible for this study if you are aged 18 or older and are scheduled to undergo mastectomy or lumpectomy for invasive breast cancer

Study details
All participants in this study will take oral capsules of the study medication for at least 21 days and up to the day of their surgery. Before and after treatment, participants will provide a tumour biopsy and blood sample. Additionally, participants will need to consent to their removed tissue being tested.

It is hoped this research will provide information regarding the action of (Z)-endoxifen and potentially lead to new therapeutics for breast cancer.


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
Ms Janet Rea
Address 86267 0
Atossa Genetics Inc.
107 Spring St
Seattle, WA 98104
USA
Country 86267 0
United States of America
Phone 86267 0
+ 1 206.799.7186
Fax 86267 0
Email 86267 0
janet.rea@atossagenetics.com
Contact person for scientific queries
Name 86268 0
Ms Janet Rea
Address 86268 0
Atossa Genetics Inc.
107 Spring St
Seattle, WA 98104
USA
Country 86268 0
United States of America
Phone 86268 0
+ 1 206.799.7186
Fax 86268 0
Email 86268 0
janet.rea@atossagenetics.com

No data has been provided for results reporting
Summary results
Not applicable