An Open Label Phase I Dose Escalation Trial of Intravenous BI 6727 in Combination With Oral BIBW 2992 in Patients With Advanced Solid Tumours With Repeated Administration in Patients With Clinical Benefit
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 3
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLT)
研究概览
简要总结
The primary objective of the current study is to investigate the Maximum Tolerated Dose (MTD) in terms of safety and tolerability of the combination of BI 6727 with BIBW 2992, in patients with advanced or metastatic solid tumours. Dosages of both BI 6727 and BIBW 2992 will be varied to establish the MTD of the combination. Two combination treatment schedules will be tested, the MTD of each combination will be determined.
Secondary objectives are the exploration of pharmacokinetics, overall safety and preliminary efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
two experimental arms
patients receive increasing doses of BI 6727 in combination with increasing doses of BIBW 2992
干预措施: BI 6727 + BIBW 2992 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLT)
时间窗: 22 Days
MTD was defined on the basis of DLTs occuring during Cycle 1 of the dose escalation part in each of the 2 treatment schedules. DLTs were defined as drug related based on Common Terminology Criteria for AE's (CTCAE) Grade(G) :1) G4 neutropenia (ANC, including bands, \<500/mm³) for more than 7 days, 2) G3 or 4 neutropenia associated with fever \>38.5° C (febrile neutropenia),3) Neutropenic infection G ≥3, 4) G4 thrombocytopenia or G3 thrombocytopenia associated with bleeding requiring whole blood transfusion.5) Non-haematological G ≥3 toxicity excluding: (a) untreated G3 diarrhoea, (b) untreated G3 nausea and/or vomiting, (c) untreated G3 rash. 6) G2 increase in AST and/or ALT in conjunction with an elevated bilirubin level of G ≥2, 7) G2 nausea and/or vomiting despite optimal supportive/antiemetic treatment for at least 7consecutive days. 8) G2 diarrhoea for 2 or more consecutive days despite antidiarrhoeal medication/hydration, 9) Decrease in left ventricular function G ≥2.
Maximum Tolerable Dose (MTD) of Two Combination Therapy of Volasertib and Afatinib.
时间窗: MTD was assessed during the first cycle of combination of Volasertib and Afatinib therapy (22 days)
Maximum Tolerable Dose (MTD) was determined by dose escalation for volasertib and afatinib. The "3 + 3 design with de-escalation" for both the Schedules A and B. Patients were sequentially allocated to the dose cohorts. Apart from allocation to the treatment schedules, escalation and/or de-escalation to determine the MTD occurred independently within the 2 dose schedules. Cohorts of 3 patients were to be treated at the starting dose levels according to the treatment schedule. Before entering patients at a higher dose level, all patients at the previous dose level combination had to complete at least the initial cycle of 21 days.
次要结局
- Number of Patients With Drug-related Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE) Criteria v 3.0(After the first drug administration until 28 days after the last drug administration, up to 413 days.)
- Number of Patients With Objective Response (OR)(Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).)
- Number of Patients With Best Overall Response.(Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).)
- Number of Patients With Disease Control(Tumor assessment was performed at screening and at the end of every 3 treatment cycle (ie every 9 weeks of treatment).)