Phase II Study of Estradiol Therapy to Target ER-Mutant and ER-Wild-Type ER+ Metastatic or Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Clinical Benefit Rate
研究概览
简要总结
Determine whether subjects harboring ESR1-mutant/amplified breast cancer have a higher rate of clinical benefit from 17b-estradiol therapy than subjects with ESR1-wild-type breast cancer
详细描述
Patients with endocrine-resistant breast cancer are eligible. Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined. Observational Phase (optional): After disease progression on 17b-estradiol, patients will be treated at their oncologist's discretion. Clinical benefit, progression-free survival, and objective response will be measured during this line of treatment of physician's choice until another instance of disease progression. In consented subjects who undergo a clinically indicated tumor biopsy of recurrent or metastatic disease prior to the start of 17b-estradiol treatment, when feasible, acquisition of additional tumor tissue is requested for research purposes. Optional: patients will be asked to provide tumor tissue via a research biopsy on Day 3-4 of 17b-estradiol treatment. Archived tumor tissue and clinical-grade tumor and plasma DNA/RNA sequencing results will be used for research purposes. Blood samples will be obtained at baseline, on Day 3-4 of 17b-estradiol therapy (optional), and upon disease progression on 17b-estradiol. Plasma and buffy coat will be extracted and frozen. Tumor tissue and plasma specimens will be analyzed to identify molecular biomarkers predictive of sensitivity/resistance to 17b-estradiol therapy
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Post-menopausal women with ER+ breast cancer.
- •Metastatic or locoregional recurrence not amenable to treatment with curative
- •Received ≥1 prior line of endocrine-based therapy (e.g., including tamoxifen, aromatase inhibitors, fulvestrant, or combinations) in the advanced/metastatic setting
排除标准
- •During the study Treatment Phase with 17b-estradiol, no concurrent anti-cancer therapies are allowed with the following exceptions:
- •Exception: Trastuzumab is allowed for the treatment of subjects with a history of HER2+ disease, and will be used at the physician's discretion.
- •Exception: Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
- •Any investigational cancer therapy in the last 3 weeks.
- •Known CNS disease, unless clinically stable for ≥ 3 months.
- •History of any of the following:
- •Deep venous thrombosis.
- •Pulmonary embolism.
- •Acute myocardial infarction.
- •Congestive heart failure.
- •Previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%.
研究组 & 干预措施
Treatment Arm
Treatment Phase: Patients will be treated with 17b-estradiol until disease progression. At this point, the patient will end protocol therapy
干预措施: Estradiol (Drug)
结局指标
主要结局
Clinical Benefit Rate
时间窗: 12 months
The clinical benefit rate (complete responses + partial responses + stable disease at 24 weeks) will be ascertained and compared between subjects treated with 17b-estradiol harboring amplified/mutant ESR1 and wild-type ESR1.
次要结局
- Progression-free survival(12 months)
- Objective response rate(8 weeks)
- Tumor Metabolic response(12 months)
- Adverse event profiles(12 months)
研究者
Muhammad.Z.Afzal
Associate Professor of Medicine
Dartmouth-Hitchcock Medical Center