Phase 1b Study of Olaparib and Estradiol in Advanced ER+ Breast Cancer (PHOEBE)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Determine the Phase II dose of olaparib in combination with 17b-estradiol
研究概览
简要总结
Determine the safety and recommended Phase II dose of olaparib in combination with 17b-estradiol in post-menopausal patients with advanced ER+/HER2- breast cancer.
详细描述
Patients with endocrine-resistant ER+/HER2- breast cancer are eligible. Patients will be treated with the combination of 17b-estradiol and olaparib for 2 cycles, and then treated with single-agent 17b-estradiol until disease progression. Clinical benefit, progression-free survival, objective response, tumor metabolic response, and toxicity will be determined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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+/HER2- breast cancer.
- •Metastatic or locoregional recurrence not amenable to treatment with curative intent.
- •Received ≥1 prior line of endocrine-based therapy in the advanced/metastatic setting.
排除标准
- •During study treatment, no concurrent anti-cancer therapies are allowed with the following exceptions:
- •o Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) permitted.
- •Any investigational cancer therapy or systemic chemotherapy in the last 3 weeks.
- •Any radiation therapy in the last 2 weeks.
- •Known CNS disease, unless clinically stable for ≥ 3 months.
- •Concomitant use of known strong or moderate CYP3A inhibitors.
- •Persistent toxicities (≥CTCAE grade 2) caused by previous cancer therapy.
- •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%
- •Severe renal impairment (creatinine clearance ≤ 30 mL/min).
研究组 & 干预措施
Treatment Arm
Participants receive 2 cycles of olaparib in combination with 17b-estradiol and then continue to be treated with single-agent 17b-estradiol until disease progression.
干预措施: Olaparib (Drug)
Treatment Arm
Participants receive 2 cycles of olaparib in combination with 17b-estradiol and then continue to be treated with single-agent 17b-estradiol until disease progression.
干预措施: 17b-estradiol (Drug)
结局指标
主要结局
Determine the Phase II dose of olaparib in combination with 17b-estradiol
时间窗: 8 weeks
Determine the safety and recommended Phase II dose of olaparib in combination with 17b-estradiol in post-menopausal patients with advanced ER+/HER2- breast cancer.
次要结局
- Progression-free survival(12 months)
- Clinical benefit rate(6 months)
- Objective response rate(6 months)
- Plasma Olaparib concentration(6 hours)
- Plasma 17b-Estradiol/Estrone concentration(6 hours)
研究者
Mary D Chamberlin
Associate Professor of Medicine
Dartmouth-Hitchcock Medical Center