A Window of Opportunity Study of Endocrine Therapy With and Without Prometrium in Postmenopausal Women With Early Stage Hormone Receptor-positive Breast Cancer.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Geometric mean suppression of proliferation marker Ki67
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Letrozole
Letrozole 2.5mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
干预措施: Letrozole (Drug)
Letrozole and Prometrium
Letrozole 2.5mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
干预措施: Letrozole and Prometrium (Drug)
Tamoxifen and Prometrium
Tamoxifen 20mg PO daily and Prometrium 300mg PO daily for 14 days between diagnosis of breast cancer and definite surgery
干预措施: Tamoxifen and Prometrium (Drug)
结局指标
主要结局
Geometric mean suppression of proliferation marker Ki67
时间窗: After two weeks of intervention, compared with baseline
The geometric mean suppression of the centrally assessed proliferation marker Ki67, after two weeks of intervention, compared with baseline
次要结局
- Safety and tolerability: number of participants with treatment-related adverse events as assessed by CTCAE v4.0(2 years)
研究者
Elgene Lim
Associate Professor
St Vincent's Hospital, Sydney