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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)

Primary Purpose

Early-stage Breast Cancer, Hormone Receptor Positive Tumor

Status
Unknown status
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Letrozole
Letrozole and Prometrium
Tamoxifen and Prometrium
Sponsored by
St Vincent's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Early-stage Breast Cancer focused on measuring early stage breast cancer, prometrium, progesterone, post-menopausal, endocrine therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologically confirmed ER+ and PR+ breast cancer (defined as ≥10% positive staining cells)
  2. Histologically confirmed HER2-negative breast cancer (defined as IHC 0-1 and/or FISH/CISH <2.2)
  3. Tumour size ≥1 cm as measured by ultrasound and/or mammogram
  4. 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
  5. Aged 18 years or older

Exclusion Criteria:

  1. Women currently on hormone therapies, including hormone replacement therapy and oral contraceptive pill
  2. Locally advanced/inoperable and inflammatory breast cancer
  3. Planned for a mastectomy (due to increased risk of venous thromboembolism)
  4. Clinical evidence of metastatic disease
  5. Patients treated with other preoperative systemic therapies
  6. Nut allergy (prometrium contains peanut oil)
  7. Prior history of uterine cancer, deep vein thrombosis, pulmonary embolism or clotting disorder
  8. Women who are pregnant or breast-feeding

Sites / Locations

  • St Vincent's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Letrozole

Letrozole and Prometrium

Tamoxifen and Prometrium

Arm Description

Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)

Full Information

First Posted
September 18, 2018
Last Updated
September 23, 2021
Sponsor
St Vincent's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03906669
Brief Title
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.
Acronym
WinPro
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 20, 2018 (Actual)
Primary Completion Date
April 2022 (Anticipated)
Study Completion Date
April 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St Vincent's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early-stage Breast Cancer, Hormone Receptor Positive Tumor
Keywords
early stage breast cancer, prometrium, progesterone, post-menopausal, endocrine therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Letrozole
Arm Type
Active Comparator
Arm Description
Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
Arm Title
Letrozole and Prometrium
Arm Type
Experimental
Arm Description
Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
Arm Title
Tamoxifen and Prometrium
Arm Type
Experimental
Arm Description
Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
PO daily for 14 days
Intervention Type
Drug
Intervention Name(s)
Letrozole and Prometrium
Intervention Description
PO daily for 14 days
Intervention Type
Drug
Intervention Name(s)
Tamoxifen and Prometrium
Intervention Description
PO daily for 14 days
Primary Outcome Measure Information:
Title
Geometric mean suppression of proliferation marker Ki67
Description
The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline
Time Frame
After two weeks of intervention, compared with baseline
Secondary Outcome Measure Information:
Title
Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Safety and tolerability of combination therapy (NCI-CTCAE v4.0)
Time Frame
2 years
Other Pre-specified Outcome Measures:
Title
Define a gene set as a predictive biomarker for a reduction in Ki67
Description
Expression of gene signature will be tested in the pre- and post-intervention tissues using the Nanostring nCounter system
Time Frame
4 years
Title
Evaluate changes in the apoptotic markers Bcl-2 and Caspase 3 in the tumors following intervention
Description
Immunohistochemistry of the pre and post intervention tissue samples
Time Frame
4 years
Title
Evaluate changes in ER, PR, AR, FoxA1, Cyclin D1 protein and mRNA expression in the tumors following intervention
Description
Immunohistochemistry of the pre and post intervention tissue samples
Time Frame
4 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Robert Kent
Phone
+61293555611
Email
SVHS.CancerResearch@svha.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elgene Lim, MBBS FRACP PhD
Organizational Affiliation
Garvan Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
St Vincent's Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Kent
Phone
+61293555611
Email
svhs.cancerresearch@svha.org.au

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26153859
Citation
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].
Results Reference
background
PubMed Identifier
27729416
Citation
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.
Results Reference
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Learn more about this trial

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.

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