- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03906669
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. (WinPro)
A Window of Opportunity Study of Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Hormone Receptor-positive Breast Cancer.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Robert Kent
- Phone Number: +61293555611
- Email: svhs.cancerresearch@svha.org.au
Study Locations
-
-
New South Wales
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Sydney, New South Wales, Australia, 2010
- Recruiting
- St Vincent's Hospital
-
Contact:
- Robert Kent
- Phone Number: +61293555611
- Email: svhs.cancerresearch@svha.org.au
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Letrozole
Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
|
PO daily for 14 days
|
Experimental: Letrozole and Prometrium
Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
|
PO daily for 14 days
|
Experimental: Tamoxifen and Prometrium
Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
|
PO daily for 14 days
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
After two weeks of intervention, compared with baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: 2 years
|
Safety and tolerability of combination therapy (NCI-CTCAE v4.0)
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Define a gene set as a predictive biomarker for a reduction in Ki67
Time Frame: 4 years
|
Expression of gene signature will be tested in the pre- and post-intervention tissues using the Nanostring nCounter system
|
4 years
|
Evaluate changes in the apoptotic markers Bcl-2 and Caspase 3 in the tumors following intervention
Time Frame: 4 years
|
Immunohistochemistry of the pre and post intervention tissue samples
|
4 years
|
Evaluate changes in ER, PR, AR, FoxA1, Cyclin D1 protein and mRNA expression in the tumors following intervention
Time Frame: 4 years
|
Immunohistochemistry of the pre and post intervention tissue samples
|
4 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Elgene Lim, MBBS FRACP PhD, Garvan Research Institute
Publications and helpful links
General 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. Erratum In: Nature. 2015 Oct 1;526(7571):144. Serandour, Aurelien A A[Corrected to Serandour, Aurelien A].
- Lim 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Bone Density Conservation Agents
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Progestins
- Letrozole
- Tamoxifen
- Progesterone
Other Study ID Numbers
- ACTRN1261000928213
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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