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)

St Vincent's Hospital

Status and phase: Enrolling; Phase 2

Conditions: Hormone Receptor Positive Tumor; Early-stage Breast Cancer

Treatments: Drug: Tamoxifen and Prometrium; Drug: Letrozole; Drug: Letrozole and Prometrium

Study type: Interventional

Funder types: Other

Identifiers

NCT03906669

ACTRN1261000928213

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Letrozole

Active Comparator group

Description:

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

Treatment:

Drug: Letrozole

Letrozole and Prometrium

Experimental group

Description:

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

Treatment:

Drug: Letrozole and Prometrium

Tamoxifen and Prometrium

Experimental group

Description:

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

Treatment:

Drug: Tamoxifen and Prometrium