Phase I Open Label Trial to Assess Safety of BIBW 2992 With Vinorelbine in Solid Tumors Known to Overexpress HER2 and/or EGFR
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 2
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLT)
研究概览
简要总结
To determine the maximum tolerated dose, safety, pharmacokinetics and anti-tumour efficacy of oral BIBW 2992 in combination with intravenous or oral vinorelbine
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BIBW 2992 and vinorelbine i.v
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine i.v.
干预措施: BIBW 2992 low (20mg) dosage (Drug)
BIBW 2992 and vinorelbine i.v
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine i.v.
干预措施: BIBW 2992 medium (40mg) dosage (Drug)
BIBW 2992 and vinorelbine i.v
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine i.v.
干预措施: BIBW 2992 high (50mg) dosage (Drug)
BIBW 2992 and vinorelbine i.v
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine i.v.
干预措施: Vinorelbine i.v. 25 mg/m² (Drug)
BIBW 2992 and vinorelbine per os
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.
干预措施: BIBW 2992 low (20mg) dosage (Drug)
BIBW 2992 and vinorelbine per os
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.
干预措施: BIBW 2992 medium (40mg) dosage (Drug)
BIBW 2992 and vinorelbine per os
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.
干预措施: BIBW 2992 high (50mg) dosage (Drug)
BIBW 2992 and vinorelbine per os
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.
干预措施: Vinorelbine per os 60 mg/m² (Drug)
BIBW 2992 and vinorelbine per os
Daily low (20mg), medium (40mg) and high (50mg) dosages of BIBW 2992 with standard dosage of vinorelbine per os.
干预措施: Vinorelbine per os 80 mg/m² (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLT)
时间窗: 28 days
Number of participants with DLT for the determination of the Maximum Tolerated Dose (MTD). 3+3 dose escalation design. MTD based on DLTs during first treatment course. After MTD was determined, additional patients were included at the MTD in an expansion cohort.
次要结局
- Number of Patients With Objective Response (OR)(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Number of Patients With Disease Control (DC)(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Time to Objective Response(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Duration of Disease Control(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Time From Dosing to the Maximum Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Time From Dosing to the Maximum Concentration of Vinorelbine After Single and Multiple Intravenous Administrations of 25mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Area Under the Concentration-time Curve of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 60mg/m^2 Per os Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h,, 7h and 24h after dosing)
- Area Under the Concentration-time Curve of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing)
- Number of Patients With Best Overall Response(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Best Percentage Change in Tumour Size(Screening and every 8 weeks after starting of treatment, up to 44 weeks.)
- Progression-free Survival (PFS)(From first dose of study medication to the occurrence of progression or death whichever came first, up to 44 months.)
- Area Under the Concentration-time Curve of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Area Under the Concentration-time Curve of Vinorelbine After Single and Multiple Intravenous Administrations of 25mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 i.v. Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Maximum Measured Concentration of Vinorelbine After Single and Multiple Intravenous Administrations of 25 mg/m^2 Vinorelbine in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Duration of Objective Response(From first dose of study medication to response measurement, up to 44 months. Tumour assessments were performed at screening, week 8, week 16, week 24, and every 8 weeks thereafter.)
- Maximum Measured Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 25mg/m^2 Per os Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing)
- Maximum Measured Concentration of Vinorelbine After Multiple Administrations Per os of 60mg/m^2 in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 0.10h, 0.30h, 1h, 4h, 7h, 24h and 168h after dosing, 0.05 hours (h) before dosing at day 15 and day 21 and 0.10h, 0.30h, 1h, 2h, 3h, 4h, 6h, 7h and 24h after dosing)
- Time From Dosing to the Maximum Concentration of Afatinib After Multiple Administrations of 40mg Afatinib in Presence and Absence of 60mg/m^2 Per os Vinorelbine at Steady State(0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing)
- Time From Dosing to the Maximum Concentration of Vinorelbine After Single and Multiple Administrations of 60mg/m^2 Vinorelbine Per os in Presence and Absence of Afatinib at Steady State(0.05 hours (h) before dosing at day 1 and 1h, 1.30h, 2h, 3h, 6h, 7h and 24h after dosing)