A Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of GDC-0032 in Combination With Docetaxel or With Paclitaxel in Patients With HER2-negative Locally Recurrent or Metastatic Breast Cancer or Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 14
- 主要终点
- Safety: Incidence of dose limiting toxicities
研究概览
简要总结
This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics of oral GDC-0032 administered in combination with either docetaxel or with paclitaxel. Patients treated with the GDC-0032 and docetaxel have HER2-negative locally recurrent or metastatic breast cancer or non-small cell lung cancer (NSCLC). Patients treated with the GDC-0032 and paclitaxel combination have human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer. There are two potential stages within each arm of this study: a dose-escalation stage (Stage 1) and a dose-expansion stage (Stage 2). Once the maximum tolerated dose of GDC-0032 in a given arm has been established from dose escalation, additional patients with each combination will be enrolled in Stage 2.
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
- •Age >=18 years
- •For paclitaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease
- •For docetaxel combination arms: histologically or cytologically documented adenocarcinoma of the breast with locally recurrent or metastatic disease or histologically documented advanced (Stage IV) or recurrent NSCLC
- •For participants with breast cancer: HER2-negative disease as defined by local clinical guidelines
- •Participants with NSCLC to be treated with docetaxel need to have received at least one prior anti-cancer treatment regimen in an advanced setting and to have docetaxel be considered appropriate treatment
- •Evaluable or measurable disease per response evaluation criteria in solid tumors (RECIST) v.1.1
- •Life expectancy >=12 weeks
- •Eastern cooperative oncology group (ECOG) performance status of 0 or 1 at screening
- •Adequate hematologic and end organ function
- •Use of highly effective form of contraception
排除标准
- •Prior anti-cancer therapy
- •Prior treatment with phosphoinositide 3-kinase (PI3K) inhibitor
- •Known significant hypersensitivity to any components of study treatment
- •Grade >=2 peripheral neuropathy
- •Type 1 or Type 2 diabetes
- •Grade >=2 hypercholesterolemia or hypertriglyceridemia
- •Congenital long QT syndrome
- •Active congestive heart failure or ventricular arrhythmia
研究组 & 干预措施
Arm A: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily for 21 consecutive days (beginning from Day 1) in each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Arm A: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily for 21 consecutive days (beginning from Day 1) in each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: GDC-0032 (Drug)
Arm B: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily for 28 consecutive days (beginning from Day 1) in each 28-day cycle along with Paclitaxel on Days 1, 8, 15 and 22 of each 28-day cycle.
干预措施: GDC-0032 (Drug)
Arm B: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily for 28 consecutive days (beginning from Day 1) in each 28-day cycle along with Paclitaxel on Days 1, 8, 15 and 22 of each 28-day cycle.
干预措施: Paclitaxel (Drug)
Arm C: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Day 1 and Days 8-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Arm C: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Day 1 and Days 8-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: GDC-0032 (Drug)
Arm D: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Days 2-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Arm D: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Days 2-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: GDC-0032 (Drug)
Arm E: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Days 1-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Arm E: GDC-0032 + Docetaxel
Participants will receive GDC-0032 once daily on Days 1-14 of each 21-day cycle along with Docetaxel on Day 1 of each 21-day cycle.
干预措施: GDC-0032 (Drug)
Arm F: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily on a 5-days on, 2-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle.
干预措施: GDC-0032 (Drug)
Arm F: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily on a 5-days on, 2-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle.
干预措施: Paclitaxel (Drug)
Arm G: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily on a 3-days on, 4-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle.
干预措施: GDC-0032 (Drug)
Arm G: GDC-0032 + Paclitaxel
Participants will receive GDC-0032 once daily on a 3-days on, 4-days off schedule in each 28-day cycle along with Paclitaxel on Days 1, 8, 5 and 22 of each 28-day cycle.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Safety: Incidence of dose limiting toxicities
时间窗: Up to 28 days
Safety: Incidence of adverse events
时间窗: Approximately 3 years
次要结局
- Time to maximum observed plasma concentration (Tmax)(Up to 28 days)
- Area under the curve from time 0 to the last measurable concentration (AUC0-last)(Up to 28 days)
- Maximum observed plasma concentration (Cmax)(Up to 28 days)
- Minimum observed plasma concentration (Cmin)(Up to 28 days)
- Objective response according to RECIST v1.1(Approximately 3 years)
- Duration of response according to RECIST v1.1(Approximately 3 years)
- Progression-free survival (PFS) according to RECIST v1.1(Approximately 3 years)