A Phase I Dose Escalation Trial of Once Daily Oral Treatment Using Afatinib (BIBW2992) Plus Gemcitabine or Docetaxel in Patients With Relapsed or Refractory Solid Tumors.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 94
- 试验地点
- 3
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
研究概览
简要总结
To establish the maximum tolerated dose (MTD) of oral afatinib (BIBW2992) given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors.
To assess the safety of the combination. To investigate the PK characteristics of docetaxel or gemcitabine and of oral afatinib (BIBW2992) in the tested treatment schedule. To assess antitumor activity.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
Afatinib and docetaxel
干预措施: Afatinib (Drug)
Afatinib and docetaxel
干预措施: docetaxel (Drug)
Afatinib and gemcitabine
干预措施: Afatinib (Drug)
Afatinib and gemcitabine
干预措施: gemcitabine (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
时间窗: 3 weeks
DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever \>38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever \>38.5º C or Grade ≥3 infection. 3. Platelet count of \<25x 10\^9/L or \<50x 10\^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0
次要结局
- Time to Objective Response According to RECIST v1.1(6 weeks, 12 weeks and 24 weeks)
- AUC 0-tz of Gemcitabine(PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3)
- The Incidence and Intensity of AEs With Grading According to CTCAE.(From first drug administration until 28 days after last drug administration, up to 717 days.)
- Best Overall Response According to RECIST v1.1 Criteria(From first drug administration until 28 days after last drug administration, up to 717 days.)
- Duration of Objective Response According to RECIST v1.1(From the first documented complete response or partial response to the time of disease progression or death)
- Cmax of Gemcitabine(PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3)
- Disease Control According to RECIST v1.1(From first drug administration until 28 days after last drug administration, up to 717 days.)
- Objective Response According to RECIST v1.1(From first drug administration until 28 days after last drug administration, up to 717 days.)
- Cmax,ss of Afatinib(PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)
- Duration of Disease Control According to RECIST v1.1(From the first administration of study medication to the time of disease progression or death)
- Volume of Distribution at Steady State (Vss) of Gemcitabine(PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3)
- AUC 0-24 of Docetaxel(PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)
- Cmax of Docetaxel(PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)
- Volume of Distribution at Steady State (Vss) of Docetaxel(PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)
- Progression Free Survival (PFS)(From the first administration of study medication to the time of disease progression or death)
- Overall Survival (OS)(From the first administration of study medication to the time of death)
- Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib(PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)
- Total Clearance (CL) of Gemcitabine(PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3)
- Total Clearance (CL) of Docetaxel(PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55)