Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination With Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer After Endocrine Failure
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 102
- 试验地点
- 8
- 主要终点
- Recommended Phase 2 dose
研究概览
简要总结
This is a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with fulvestrant in patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
The study is an open-label design, consists of 2 parts: dose-finding portion (Part 1), and expansion portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 102 patients will be enrolled in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of HR-positive, HER2-negative breast cancer, not amenable to curative therapy
- •Pre- or perimenopausal women can be enrolled if amenable to be treated with goserelin
- •Patients must satisfy 1 of the following criteria for prior therapy:
- •Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor or tamoxifen
- •Progressed during treatment or within 2 months after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer, or prior endocrine therapy for advanced/metastatic breast cancer
- •Received ≤ 2 chemotherapy regimens (Part 1) or ≤ 1 chemotherapy regimen (Part 2) for advanced/metastatic disease
- •For Part 1, evaluable or measurable disease (bone only disease eligible for Part 1 only)
- •For Part 2, measurable disease as defined by RECIST, Version 1.1
- •ECOG performance status 0 to 1
- •Adequate organ function
排除标准
- •For Part 1, prior treatment with fulvestrant
- •For Part 2, prior treatment with any CDK inhibitor or fulvestrant
- •Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
- •Chemotherapy within 21 days of first G1T38 dose
- •Investigational drug within 28 days of first G1T38 dose
- •Concurrent radiotherapy, radiotherapy within 14 days of first G1T38 dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
- •Prior hematopoietic stem cell or bone marrow transplantation
研究组 & 干预措施
Once-Daily G1T38 Dosing
G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
干预措施: G1T38 (Drug)
Once-Daily G1T38 Dosing
G1T38 (lerociclib) orally (once daily) in combination with fulvestrant.
干预措施: Fulvestrant (Drug)
Twice-Daily G1T38 Dosing
G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
干预措施: G1T38 (Drug)
Twice-Daily G1T38 Dosing
G1T38 (lerociclib) orally (twice daily) in combination with fulvestrant.
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Recommended Phase 2 dose
时间窗: 14 months
Recommended Phase 2 dose interval
时间窗: 14 months
Twice-Daily or Once-Daily dosing
Dose Limiting Toxicity
时间窗: Week 1 Day 1-Week 5 Day 1
Number of Treatment Related Adverse Event, including Abnormal Laboratory Events
时间窗: 36 months
All AEs, including clinical laboratory, vitals signs, physical examinations and ECGs will be analyzed in all patients receiving study drug from the signing of the informed consent until 30 days after the last dose of study medication up to 36 months
次要结局
- Tumor response based on RECIST, Version 1.1(30 months)
- Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Maximum Plasma Concentration (Cmax)(Week 1 Day 1-Week 9 Day 1)
- Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma: terminal half life (T1/2)(Week 1 Day 1-Week 9 Day 1)
- Progression free survival (PFS)(36 months)
- Overall survival (OS)(48 months)
- Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Area under Curve - plasma concentration (AUC)(Week 1 Day 1-Week 9 Day 1)
- Pharmacokinetics of G1T38, Fulvestrant, and Goserelin: Plasma - Volume of distribution(Week 1 Day 1-Week 9 Day 1)