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.

NCT ID: NCT03906669

Last Updated: 2023-11-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-20

Study Completion Date

2024-04-30

Brief Summary

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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

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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.

Conditions

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Early-stage Breast Cancer Hormone Receptor Positive Tumor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Letrozole

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

Group Type ACTIVE_COMPARATOR

Letrozole

Intervention Type DRUG

PO daily for 14 days

Letrozole and Prometrium

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

Group Type EXPERIMENTAL

Letrozole and Prometrium

Intervention Type DRUG

PO daily for 14 days

Tamoxifen and Prometrium

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

Group Type EXPERIMENTAL

Tamoxifen and Prometrium

Intervention Type DRUG

PO daily for 14 days

Interventions

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Letrozole

PO daily for 14 days

Intervention Type DRUG

Letrozole and Prometrium

PO daily for 14 days

Intervention Type DRUG

Tamoxifen and Prometrium

PO daily for 14 days

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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St Vincent's Hospital

OTHER

Sponsor Role lead

Responsible Party

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Elgene Lim

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Elgene Lim, MBBS FRACP PhD

Role: PRINCIPAL_INVESTIGATOR

Garvan Research Institute

Locations

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St Vincent's Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Robert Kent

Role: CONTACT

+61293555611

Facility Contacts

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Robert Kent

Role: primary

+61293555611

References

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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.

Reference Type BACKGROUND
PMID: 26153859 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27729416 (View on PubMed)

Other Identifiers

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ACTRN1261000928213

Identifier Type: -

Identifier Source: org_study_id