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.

Early-stage Breast Cancer Clinical Trial

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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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03906669
• Other study ID #: ACTRN1261000928213
• Status: Recruiting
• Phase: Phase 2
• Start date: March 20, 2018
• Est. completion date: April 2024

Study information

• Verified date: November 2023
• Source: St Vincent's Hospital
• Contact: Robert Kent
• Phone: +61293555611
• Email: SVHS.CancerResearch[@]svha.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: April 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Early-stage Breast Cancer
• Hormone Receptor Positive Tumor

Intervention

Drug:
• Letrozole
PO daily for 14 days
• Letrozole and Prometrium
PO daily for 14 days
• Tamoxifen and Prometrium
PO daily for 14 days

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Sydney	New South Wales

Sponsors (1)

Lead Sponsor	Collaborator
St Vincent's Hospital

Country where clinical trial is conducted

Australia, 

References & Publications (2)

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. — View 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]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Define a gene set as a predictive biomarker for a reduction in Ki67	Expression of gene signature will be tested in the pre- and post-intervention tissues using the Nanostring nCounter system	4 years
Other	Evaluate changes in the apoptotic markers Bcl-2 and Caspase 3 in the tumors following intervention	Immunohistochemistry of the pre and post intervention tissue samples	4 years
Other	Evaluate changes in ER, PR, AR, FoxA1, Cyclin D1 protein and mRNA expression in the tumors following intervention	Immunohistochemistry of the pre and post intervention tissue samples	4 years
Primary	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	After two weeks of intervention, compared with baseline
Secondary	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)	2 years