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Trial registered on ANZCTR


Registration number
ACTRN12618000928213
Ethics application status
Approved
Date submitted
29/05/2018
Date registered
1/06/2018
Date last updated
3/07/2019
Date data sharing statement initially provided
7/05/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Progesterone as an anticancer therapy in breast cancer
Scientific title
An open-label, randomized, window of opportunity study between diagnosis and definite surgery, to assess the effect of antiestrogen therapies, alone and in combination with microionized progesterone (prometrium) in patients with newly diagnosed ER+PR+ breast cancer.
Secondary ID [1] 290047 0
None
Universal Trial Number (UTN)
Trial acronym
WinPro
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 300101 0
Condition category
Condition code
Cancer 299986 299986 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two weeks of preoperative systemic therapy with either 1) letrozole 2.5mg oral tablet daily, 2) letrozole 2.5mg + promethium 300mg oral tablets daily, and 3) tamoxifen 20mg + prometrium 300mg oral tablets daily, between diagnosis of breast cancer and definite surgery.
Intervention code [1] 295772 0
Treatment: Drugs
Comparator / control treatment
Two weeks of preoperative systemic therapy with Letrozole 2.5mg oral tablet daily, between diagnosis of breast cancer and definite surgery.
Control group
Active

Outcomes
Primary outcome [1] 299467 0
This outcome is assessed by immunohistochemistry on the paired tumour samples, comparing pre treated tumour from diagnostic sample, and post-treated samples at surgery. The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of treatment, compared with baseline. This will be obtained by comparing the mean difference in Ki67 staining between pre and post-treated samples in each treatment arm.
Timepoint [1] 299467 0
At time of definitive surgery, which follows 2 weeks of therapy.
Secondary outcome [1] 327265 0
Safety of combination therapy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.0).
Timepoint [1] 327265 0
At time of definitive surgery, which follows 2 weeks of therapy.
Secondary outcome [2] 347518 0
Tolerability of combination therapy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v 4.0).
Timepoint [2] 347518 0
At time or surgery and at the post surgery follow up visit
Secondary outcome [3] 347529 0
Translational studies on potential biomarkers of response (Blood and tumour tissue)
Timepoint [3] 347529 0
These will be collected prior to and at the time of surgery.

Eligibility
Key inclusion criteria
1. Post-menopausal women defined by any one of the following criteria;
a) Amenorrhea >12 months at the time of diagnosis and an intact uterus, with FSH and estradiol in the postmenopausal ranges,
b) prior bilateral oophorectomy, and
c) FSH and estradiol levels within the postmenopausal range (as per local practice) in women aged <55years who have undergone hysterectomy.
2. Histologically confirmed ER+ and PR+ breast cancers (defined as >10% positive staining cells)
3. HER2/CEP17 ratio of <2 (as per the ASCO CAP guidelines)
4. Tumour size >1cm as measured by ultrasound and/or mammogram
5. Ability to understand all patient information and informed-consent documents, written informed consent to participate in the trial, and to avail tissue and blood samples for research
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women currently on hormone therapies
2. Locally advanced/inoperable and inflammatory breast cancer
3. Clinical evidence of metastatic disease
4. Patients treated with other preoperative systemic therapies
5. Nut allergy (prometrium contains peanut oil)
6. Prior history of uterine cancer, deep vein thrombosis or pulmonary embolism.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
There are three potential comparisons:
1. Letrozole alone vs letrozole + Prometrium;
2. Letrozole alone vs tamoxifen + Prometrium; and
3. Letrozole + Prometrium vs tamoxifen + Prometrium
The baseline expectation for the letrozole alone arm is based on the biomarker changes seen in the IMPACT study (Dowsett et al, Clin Cn Res 2005), in which at 2 weeks anastrozole (an aromatse inhibitor) caused a geometric mean reduction of 76% in Ki67. This allows estimation of power to detect differences between arm 1 and either arm 2 or arm 3. For the third possible comparison (Arm 2 vs Arm 3) there is no obvious prior evidence. We will therefore treat this as a purely exploratory comparison and test the other 2 at a p-value of 0.025 each. With a total trial recruitment of 200 and allowing 4% dropouts, this would give 80% power to detect an improvement in Ki67 suppression from 76% in the letrozole alone control arm to 92% in either experimental arm.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
21/03/2018
Date of last participant enrolment
Anticipated
31/03/2020
Actual
Date of last data collection
Anticipated
31/05/2020
Actual
Sample size
Target
200
Accrual to date
29
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 6564 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 6567 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 6572 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 11033 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [5] 11034 0
Sydney Adventist Hospital - Wahroonga
Recruitment hospital [6] 11040 0
Calvary North Adelaide Hospital - North Adelaide
Recruitment postcode(s) [1] 14162 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 14165 0
3050 - Parkville
Recruitment postcode(s) [3] 14170 0
2050 - Camperdown
Recruitment postcode(s) [4] 22829 0
2560 - Campbelltown
Recruitment postcode(s) [5] 22830 0
2076 - Wahroonga
Recruitment postcode(s) [6] 22836 0
5006 - North Adelaide

Funding & Sponsors
Funding source category [1] 294417 0
Government body
Name [1] 294417 0
Cancer Council of NSW
Country [1] 294417 0
Australia
Primary sponsor type
Other
Name
St Vincent's Hospital, Sydney
Address
370 Victoria St
Darlinghurst 2010
NSW
Country
Australia
Secondary sponsor category [1] 293265 0
None
Name [1] 293265 0
Address [1] 293265 0
Country [1] 293265 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295835 0
St Vincent’s Hospital Human Research Ethics Committee
Ethics committee address [1] 295835 0
Ethics committee country [1] 295835 0
Australia
Date submitted for ethics approval [1] 295835 0
12/10/2017
Approval date [1] 295835 0
22/11/2017
Ethics approval number [1] 295835 0
HREC17/SVH/255

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

Contacts
Principal investigator
Name 68682 0
A/Prof Elgene Lim
Address 68682 0
The Kinghorn Cancer Centre
370 Victoria St
Darlinghurst, NSW 2010
Country 68682 0
Australia
Phone 68682 0
+61 2 9355 5600
Fax 68682 0
+61 2 9355 5602
Email 68682 0
e.lim@garvan.org.au
Contact person for public queries
Name 68683 0
Lauren Armstrong
Address 68683 0
The Kinghorn Cancer Centre
370 Victoria St
Darlinghurst, NSW 2010
Country 68683 0
Australia
Phone 68683 0
+61 2 9355 5783
Fax 68683 0
+61 2 9355 5735
Email 68683 0
svhs.winpro@svha.org.au
Contact person for scientific queries
Name 68684 0
Christopher Rofe
Address 68684 0
The Kinghorn Cancer Centre
370 Victoria St
Darlinghurst, NSW 2010
Country 68684 0
Australia
Phone 68684 0
+61 2 9355 5708
Fax 68684 0
+61 2 9355 5735
Email 68684 0
christopher.rofe@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not apart of our ethics approved protocol


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
SourceTitleYear of PublicationDOI
Dimensions AIProgesterone and Progesterone Receptors in Breast Cancer: Past, Present, Future2020https://doi.org/10.1530/jme-20-0104
N.B. These documents automatically identified may not have been verified by the study sponsor.