Phase II Randomized Trial of the Polo-like Kinase 1 Inhibitor BI 6727 Monotherapy Versus Investigator´s Choice Chemotherapy in Ovarian Cancer Patients Resistant or Refractory to Platinum-based Cytotoxic Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 110
- 试验地点
- 31
- 主要终点
- Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
研究概览
简要总结
This is an international, randomized phase II trial. The aim is to assess the efficacy and the safety of BI 6727 Versus investigator's best choice single agent cytotoxic in recurrent third and fourth lines platinum resistant/refractory ovarian cancer.
100 patients will be randomised at the study entry to receive either BI 6727 (Arm A: 50 patients) or non-platinum single agent cytotoxic (Arm B: 50 patients) Treatment will be continued until disease progression or unacceptable toxicity. Primary endpoint: disease control rate at week 24 according to Response Evaluation Criteria In Solid Tumours version 1.1.
Secondary endpoints: efficacy (progression free survival, overall survival, biological tumour response, biological progression free survival assessed by serum CA 125 according to Gynecologic Cancer Intergroup criteria, safety according to the NCI CTCAE v.3, disease symptoms control assessed by the EORTC QLQ-C30, QLQ-OV28 and individual symptoms questionnaires, pharmacokinetics of BI 6727.
Others endpoints: biomarkers and pharmacogenetics analysis (optional)
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 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
BI 6727
Patients receive BI 6727 infusion every 3 weeks
干预措施: BI 6727 (Drug)
Cytotoxic
At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
干预措施: Paclitaxel (Drug)
Cytotoxic
At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
干预措施: Gemcitabine (Drug)
Cytotoxic
At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
干预措施: Topotecan (Drug)
Cytotoxic
At the investigator discretion, patient will receive one of the following cytotoxics: topotecan, paclitaxel, gemcitabine or liposomal doxorubicin
干预措施: Pegylated liposomal doxorubicin (PLD) (Drug)
结局指标
主要结局
Disease Control Rate (DCR) at Week 24 According to Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1
时间窗: Week 24
DCR was defined as the proportion of patients who had an overall response of complete response (CR), partial response (PR), or stable disease (SD).
次要结局
- AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for BI 6727 BS(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for CD 10899 BS(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Tmax; Time From Dosing to Maximum Measured Concentration of BI 6727 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- t1/2; Terminal Half-life of CD 10899 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Vss;Apparent Volume of Distribution at Steady State Following Intravenous Administration for BI 6727 BS(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Incidence and Intensity of Adverse Events According to the United States National Cancer Institute (US NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0(From first treatment administration to 21 days after the last drug administration (Up to 1403 days))
- Clinically Relevant Changes in Laboratory and ECG Data(From first treatment administration to 21 days after the last drug administration (Up to 1403 days))
- Cmax; Maximum Measured Concentration of BI 6727 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- MRT; Mean Residence Time of BI 6727 BS in the Body(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Progression Free Survival (PFS)(From randomization until disease progression, death or study discontinuation; Up to 213 weeks)
- Overall Survival (OS)(From randomization until death or study discontinuation; Up to 213 weeks)
- Biological Tumour Response Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria(At screening and every 6 weeks thereafter (Up to 213 weeks))
- Biological Progression-free Survival Based on Serum Cancer Antigen 125 (CA-125) According to the Gynaecologic Cancer Intergroup (GCIG) Criteria(At screening and every 6 weeks thereafter (Up to 213 weeks ))
- Time to Deterioration in Pain/ Quality of Life (QOL)(Every 6 weeks (Up to 213 weeks ))
- Best Overall Response(time from the date of randomisation until study completion/discontinuation; Up to 213 weeks)
- Time to Deterioration in Global Health Status/Quality of Life (QOL)(Every 6 weeks (Up to 213 weeks ))
- Time to Deterioration in Fatigue/Quality of Life (QOL)(Every 6 weeks (Up to 213 weeks ))
- Time to Deterioration in Abdominal Bloating/ Quality of Life (QOL)(Every 6 weeks (Up to 213 weeks ))
- AUC (0-24); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 to 24 Hours for CD 10899 BS(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Tmax; Time From Dosing to Maximum Measured Concentration of CD 10899 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- CL; Total Clearance of BI 6727 BS in Plasma After Intravenous Administration(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Biomarkers and Pharmacogenetics Analysis (Optional)(6 months)
- Time to Deterioration in the Three Most Troublesome Disease Specific Symptoms/ Quality of Life (QOL)(Every 6 weeks (Up to 213 weeks))
- AUC (0-inf); Area Under the Concentration-time Curve in Plasma Over the Time Interval From 0 Extrapolated to Infinity for BI 6727 BS(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- Cmax; Maximum Measured Concentration of CD 10899 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)
- t1/2; Terminal Half-life of BI 6727 BS in Plasma(-0.083 hours (h), 2h, 4h, 6h, 24h, 168h and 336 h after first drug administration)