Description:
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.
Title
- 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.
- 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 IDs
- ORG STUDY ID:
ACTRN1261000928213
- NCT ID:
NCT03906669
Conditions
- Early-stage Breast Cancer
- Hormone Receptor Positive Tumor
Interventions
Drug | Synonyms | Arms |
---|
Letrozole | | Letrozole |
Letrozole and Prometrium | | Letrozole and Prometrium |
Tamoxifen and Prometrium | | Tamoxifen and Prometrium |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Letrozole | Active Comparator | Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery | |
Letrozole and Prometrium | Experimental | Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery | |
Tamoxifen and Prometrium | Experimental | Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery | |
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Geometric mean suppression of proliferation marker Ki67 |
Time Frame: | After two weeks of intervention, compared with baseline |
Safety Issue: | |
Description: | The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline |
Secondary Outcome Measures
Measure: | Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Safety and tolerability of combination therapy (NCI-CTCAE v4.0) |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | St. Vincent's Hospital-Manhattan |
Trial Keywords
- early stage breast cancer
- prometrium
- progesterone
- post-menopausal
- endocrine therapy
Last Updated
April 8, 2019