A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 95
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
详细描述
This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm.
The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity.
To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.
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 130 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A (adavosertib + gemcitabine)
Adavosertib (175 mg PO) will be taken on Days 1-2, 8-9, and 15-16. Gemcitabine 800 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.
干预措施: Adavosertib (Drug)
Arm A (adavosertib + gemcitabine)
Adavosertib (175 mg PO) will be taken on Days 1-2, 8-9, and 15-16. Gemcitabine 800 mg/m² will be administered IV on days 1, 8, and 15 of each 28 day cycle.
干预措施: Gemcitabine (Drug)
Arm B (adavosertib + paclitaxel)
Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days weekly (Days 1-3, 8-10, and 15-17). Weekly paclitaxel 80 mg/m² IV will be administered according to institutional standards on Day 1, 8, and 15 of each 28 day cycle.
干预措施: Adavosertib (Drug)
Arm B (adavosertib + paclitaxel)
Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days weekly (Days 1-3, 8-10, and 15-17). Weekly paclitaxel 80 mg/m² IV will be administered according to institutional standards on Day 1, 8, and 15 of each 28 day cycle.
干预措施: Paclitaxel (Drug)
Arm C/C2 (adavosertib + carboplatin)
Arm C: Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days (Days 1-3). Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21-Day cycle.
Arm C2: Five doses of adavosertib (225 mg PO BID) 2.5 days per dosing week (QW), on Weeks 1 (D1-3), 2 (D8-10) and 3 (D15-17), or on Weeks 1 (D1-3) and 2 (D8-10) ( 2 weeks on followed by 1 week off.) Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21 day cycle.
干预措施: Adavosertib (Drug)
Arm C/C2 (adavosertib + carboplatin)
Arm C: Five doses of adavosertib (225 mg PO BID) will be taken in approximate 12 hour intervals over 2.5 days (Days 1-3). Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21-Day cycle.
Arm C2: Five doses of adavosertib (225 mg PO BID) 2.5 days per dosing week (QW), on Weeks 1 (D1-3), 2 (D8-10) and 3 (D15-17), or on Weeks 1 (D1-3) and 2 (D8-10) ( 2 weeks on followed by 1 week off.) Carboplatin AUC 5 IV will be administered according to institutional standards on Day 1 of each 21 day cycle.
干预措施: Carboplatin (Drug)
Arm D (adavosertib + PLD)
Five doses of adavosertib (175 mg or 225 mg) will be taken in approximate 12 hour intervals over 2.5 days (Days 1, 2, and 3) of each 28-day cycle. PLD will administered IV on Day 1 of each cycle.
干预措施: Adavosertib (Drug)
Arm D (adavosertib + PLD)
Five doses of adavosertib (175 mg or 225 mg) will be taken in approximate 12 hour intervals over 2.5 days (Days 1, 2, and 3) of each 28-day cycle. PLD will administered IV on Day 1 of each cycle.
干预措施: PLD (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Throughout the duration of the study (up to 19 months)
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
次要结局
- Duration of Response (DoR)(Throughout the duration of the study, approximately 19 months.)
- Disease Control Rate (DCR)(Throughout the duration of the study (up to 19 months))
- Progression Free Survival (Median, 95% CI)(Throughout the Study, Approximately 4 years)
- Overall Survival (Median, 80% CI)(Throughout the Study, Approximately 4 years)
- Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction(Throughout the duration of the study (up to 19 months))
- Serious Adverse Events Leading to Death(Throughout the duration of the study (up to 19 months))
- Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation(Throughout the duration of the study (up to 19 months))
- Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation(Throughout the duration of the study (up to 19 months))
- Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption(Throughout the duration of the study (up to 19 months))
- Single Dose Adavosertib Tmax(Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr)
- Progression Free Survival (Median, 80% CI)(Throughout the Study, Approximately 4 years)
- Overall Survival (Median, 95% CI)(Throughout the Study, Approximately 4 years)
- Gynecologic Cancer Intergroup (GCIG) CA-125 Response(Throughout the study, approximately 4 years)
- The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.(Throughout the duration of the study (up to 19 months))
- The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade(Throughout the duration of the study (up to 19 months))
- Serious Adverse Events(Throughout the duration of the study (up to 19 months))
- Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction(Throughout the duration of the study (up to 19 months))
- Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption(Throughout the duration of the study (up to 19 months))
- Multiple Dose Adavosertib Tmax(Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr)
- Single Dose Adavosertib Cmax(Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr)
- The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade(Throughout the duration of the study (up to 19 months))
- Multiple Dose Adavosertib Cmax(Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr)