Early-stage Breast CancerPhase 2WinProNCT03906669
A Window of Opportunity Study of Pre-operative Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Breast Hormone Receptor Positive (HR+) Human Epidermal Receptor 2 Negative (HER2-) Breast Cancer.
A Phase 2 study testing Letrozole, Letrozole and Prometrium and Tamoxifen and Prometrium in people with Early-stage Breast Cancer and Hormone Receptor Positive Tumor, run by St Vincent's Hospital at 1 site in Australia.
Trial summary
A phase II randomised, open label study of pre-operative endocrine therapy with \& without prometrium in postmenopausal women with early stage breast hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Early-stage Breast Cancer, Hormone Receptor Positive Tumor
- What is being tested?
- Letrozole, Letrozole and Prometrium and Tamoxifen and Prometrium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteAustralia
- Study dates
- 20 Mar 2018to Apr 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed ER+ and PR+ breast cancer (defined as ≥10% positive staining cells)
- Histologically confirmed HER2-negative breast cancer (defined as IHC 0-1 and/or FISH/CISH <2.2)
- Tumour size ≥1 cm as measured by ultrasound and/or mammogram
- 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
- Aged 18 years or older
Who cannot join
- Women currently on hormone therapies, including hormone replacement therapy and oral contraceptive pill
- Locally advanced/inoperable and inflammatory breast cancer
- Planned for a mastectomy (due to increased risk of venous thromboembolism)
- Clinical evidence of metastatic disease
- Patients treated with other preoperative systemic therapies
- Nut allergy (prometrium contains peanut oil)
- Prior history of uterine cancer, deep vein thrombosis, pulmonary embolism or clotting disorder
- Women who are pregnant or breast-feeding
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
St Vincent's Hospital
Sydney, New South Wales, 2010
Robert Kent, +61293555611, svhs.cancerresearch@svha.org.au
About this study
Official title: A Window of Opportunity Study of Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Hormone Receptor-positive Breast Cancer.
A phase II randomised, open label study of pre-operative endocrine therapy with \& without prometrium in postmenopausal women with early stage breast hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) breast cancer.
Read the detailed description
There is bidirectional interplay between the progesterone receptor (PR) and oestrogen receptor (ER) in human breast cancers. There is evidence for a reprogramming of ER chromatin binding sites with 470 genes differentially regulated by dual treatment with estrogen plus progestogen compared to estrogen alone in breast cancer cell lines. Functionally, there was an additive anti-cancer effect with the addition of natural progesterone to endocrine therapy in preclinical breast cancer models.
This is a phase II multi-site, randomised, open-label, three-arm, study in 200 postmenopausal women with early-stage ER+, PR+, HER2-negative breast cancer. Eligible patients will be randomised (1:1:1) to receive 14 days of intervention with either letrozole 2.5mg PO daily (arm 1), letrozole 2.5mg + prometrium 300mg PO daily (arm 2) or tamoxifen 20mg + prometrium 300mg PO daily (arm 3), between diagnosis of breast cancer and definitive surgery.
- Being tested
- Letrozole, Letrozole and Prometrium, Tamoxifen and Prometrium
- Keywords
- early stage breast cancer, prometrium, progesterone, post-menopausal, endocrine therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
PO daily for 14 days
Letrozole and PrometriumDrug
PO daily for 14 days
Tamoxifen and PrometriumDrug
PO daily for 14 days
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Active comparator | Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery Receives: Drug: Letrozole |
| Letrozole and Prometrium | Experimental | Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery Receives: Drug: Letrozole and Prometrium |
| Tamoxifen and Prometrium | Experimental | Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery Receives: Drug: Tamoxifen and Prometrium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric mean suppression of proliferation marker Ki67
The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline
Measured: After two weeks of intervention, compared with baseline
Secondary outcomes (1)
Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Safety and tolerability of combination therapy (NCI-CTCAE v4.0)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start20 Mar 2018
- Primary completionApr 2024 (estimated)
- Study completionApr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Early-stage Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St Vincent's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Elgene Lim, St Vincent's Hospital, Sydney
- Investigators
- Elgene Lim, MBBS FRACP PhD, Principal investigator, Garvan Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906669
- Sponsor's protocol ID
- ACTRN1261000928213
- Acronym
- WinPro
- Status last verified
- Nov 2023
- First submitted
- 18 Sep 2018
- Last updated
- 22 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERalpha action in breast cancer. Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8.
PubMed 26153859Lim E, Tarulli G, Portman N, Hickey TE, Tilley WD, Palmieri C. Pushing estrogen receptor around in breast cancer. Endocr Relat Cancer. 2016 Dec;23(12):T227-T241. doi: 10.1530/ERC-16-0427. Epub 2016 Oct 11.
PubMed 27729416
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Window of Opportunity Study of Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Hormone Receptor-positive Breast Cancer.
- ClinicalTrials.gov ID
- NCT03906669
- Acronym / sponsor ID
- WinPro / ACTRN1261000928213
- Keywords
- early stage breast cancer, prometrium, progesterone, post-menopausal, endocrine therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- St Vincent's HospitalUniversity, hospital or other
- Study start
- 20 Mar 2018 (actual)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 8 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A phase II randomised, open label study of pre-operative endocrine therapy with \& without prometrium in postmenopausal women with early stage breast hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) breast cancer.
Detailed description
There is bidirectional interplay between the progesterone receptor (PR) and oestrogen receptor (ER) in human breast cancers. There is evidence for a reprogramming of ER chromatin binding sites with 470 genes differentially regulated by dual treatment with estrogen plus progestogen compared to estrogen alone in breast cancer cell lines. Functionally, there was an additive anti-cancer effect with the addition of natural progesterone to endocrine therapy in preclinical breast cancer models.
This is a phase II multi-site, randomised, open-label, three-arm, study in 200 postmenopausal women with early-stage ER+, PR+, HER2-negative breast cancer. Eligible patients will be randomised (1:1:1) to receive 14 days of intervention with either letrozole 2.5mg PO daily (arm 1), letrozole 2.5mg + prometrium 300mg PO daily (arm 2) or tamoxifen 20mg + prometrium 300mg PO daily (arm 3), between diagnosis of breast cancer and definitive surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Active comparator | Drug: LetrozoleLetrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery |
| Letrozole and Prometrium | Experimental | Drug: Letrozole and PrometriumLetrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery |
| Tamoxifen and Prometrium | Experimental | Drug: Tamoxifen and PrometriumTamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically confirmed ER+ and PR+ breast cancer (defined as ≥10% positive staining cells)
- Histologically confirmed HER2-negative breast cancer (defined as IHC 0-1 and/or FISH/CISH <2.2)
- Tumour size ≥1 cm as measured by ultrasound and/or mammogram
- 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
- Aged 18 years or older
Key exclusion criteria (8 listed)
- Women currently on hormone therapies, including hormone replacement therapy and oral contraceptive pill
- Locally advanced/inoperable and inflammatory breast cancer
- Planned for a mastectomy (due to increased risk of venous thromboembolism)
- Clinical evidence of metastatic disease
- Patients treated with other preoperative systemic therapies
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetrozolePO daily for 14 days | Drug | Letrozole |
| Letrozole and PrometriumPO daily for 14 days | Drug | Letrozole and Prometrium |
| Tamoxifen and PrometriumPO daily for 14 days | Drug | Tamoxifen and Prometrium |
Primary outcome
Geometric mean suppression of proliferation marker Ki67
Time frame: After two weeks of intervention, compared with baseline
The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline
1 secondary outcome
Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2023.
- Background: PubMed 26153859Mohammed H, Russell IA, Stark R, Rueda OM, Hickey TE, Tarulli GA, Serandour AA, Birrell SN, Bruna A, Saadi A, Menon S, Hadfield J, Pugh M, Raj GV, Brown GD, D'Santos C, Robinson JL, Silva G, Launchbury R, Perou CM, Stingl J, Caldas C, Tilley WD, Carroll JS. Progesterone receptor modulates ERalpha action in breast cancer. Nature. 2015 Jul 16;523(7560):313-7. doi: 10.1038/nature14583. Epub 2015 Jul 8.
- Background: PubMed 27729416Lim E, Tarulli G, Portman N, Hickey TE, Tilley WD, Palmieri C. Pushing estrogen receptor around in breast cancer. Endocr Relat Cancer. 2016 Dec;23(12):T227-T241. doi: 10.1530/ERC-16-0427. Epub 2016 Oct 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elgene Lim, MBBS FRACP PhD principal investigator
Garvan Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Letrozole, Letrozole and Prometrium and Tamoxifen and Prometrium in people with Early-stage Breast Cancer and Hormone Receptor Positive Tumor, run by St Vincent's Hospital at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Robert Kent (+61293555611, SVHS.CancerResearch@svha.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Geometric mean suppression of proliferation marker Ki67 (time frame: After two weeks of intervention, compared with baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03906669, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2023.