A Phase I Dose Escalation Trial of BI 836845 Administered Intravenously Once Every Three Weeks in Patients With Advanced Solid Tumours During Escalation and Weekly in Selected Tumour Types During Expansion, With Repeated Administrations in Patients Showing Clinical Benefit
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) or Relevant Biological Dose (RBD) of BI 836845 During the First Treatment Course of the Dose Escalation Phase
研究概览
简要总结
This study is a phase I, open-label, dose escalation trial to determine the maximum tolerated dose (MTD) of a new drug BI 836845 which blocks the insulin growth factor (IGF) pathway believed to be involved in cancer growth. BI 836845 will be administered for the very first time into cancer patients.
The study will also look at the overall safety of the drug, and examine the drug levels in the body at specific timepoints during the trial (pharmacokinetic profile); the effect the drug may have on tumours will also be examined (pharmacodynamics).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
BI 836845 10 mg
Patients received 10 milligram (mg) of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 20 mg
Patients received 20 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 40 mg
Patients received 40 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 80 mg
Patients received 80 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 160 mg
Patients received 160 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 320 mg
Patients received 320 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 640 mg
Patients received 640 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 1280 mg
Patients received 1280 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 1800 mg
Patients received 1800 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 2400 mg
Patients received 2400 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
BI 836845 3600 mg
Patients received 3600 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1 of each 3-weekly course of treatment until disease progression or undue toxicities in the dose escalation part of the study
干预措施: BI 836845 (Drug)
Ewings sarcoma
Patients with Ewing's family of tumours (EFT) or primitive neuroectodermal tumour (PNET) receiving relevant biological dose (RBD) of BI 836845 1000 mg, administered in each course of 21 days by a 1-hour infusion at the start of each week in expansion part of the study.
干预措施: BI 836845 (Drug)
Biopsiable tumours
Patients with all solid tumour types who had tumours suitable for biopsy receiving relevant biological dose (RBD) of BI 836845 1000 mg, administered in each course of 21 days by a 1-hour infusion at the start of each week in expansion part of the study.
干预措施: BI 836845 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) or Relevant Biological Dose (RBD) of BI 836845 During the First Treatment Course of the Dose Escalation Phase
时间窗: During the first course of treatment, up to 21 days
To determine the MTD or relevant biological dose (RBD) of BI 836845 during the first treatment course of the dose escalation phase. The MTD was defined as the highest dose level of BI 836845 below the maximum dose administered at which no more than 1 out of 6 patients experienced a drug-related DLT during the first course of treatment. Starting dose of 10 mg BI 836845, administered once every 3 weeks. Dose levels evaluated were: 10 mg, 20 mg, 40 mg, 80 mg, 160 mg, 320 mg, 640 mg, 1280 mg, 1800 mg, 2400 mg, and 3600 mg. In the absence of the MTD, the RBD, where a plateau in total Insulin-like growth factor 1 (IGF-1) level and total neutralisation of IGF activity is predicted, is reported.
Percentage of Patients With Dose Limiting Toxicities (DLTs) During the First Treatment Course of the Dose Escalation Phase
时间窗: During the first course of treatment, up to 21 days
DLTs defined as drug related: CTCAE Grade 4 neutropenia lasting ≥7 days; febrile neutropenia and/or documented infection with Absolute Neutrophil Count \<1.0x109/L; Grade 4 thrombocytopaenia or Grade 3 associated with bleeding needing platelet transfusion; Grade ≥3 increased hepatic enzymes; Grade 3 or 4 non-haematologic toxicity with exceptions; Grade ≥2 infusion reaction despite adequate pre-medication; Grade ≥2 nausea and/or vomiting persisting for ≥7 days despite antiemetic treatment; Grade ≥3 skin toxicity despite adequate supportive care measures for up to 2 weeks if it does not reach an improvement to grade ≤2; Grade ≥3 hyperglycaemia resistant to treatment with anti-diabetic agents; any electrolyte grade 3 AE refractory to optimal correction therapy; no recovery from a non-DLT grade \>2 toxicity to grade 1 within 14 days of administered dose; sustained fatigue/asthenia grade 3 for \>96 h associated with deterioration of Performance score (Eastern Cooperative Oncology Group).
次要结局
- Best Overall Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Criteria Version 1.1(First treatment administration, up to 246 days.)
- Objective Tumour Response(First treatment administration, up to 246 days.)
- Duration of Objective Response(First treatment administration, up to 246 days.)
- Disease Control(First treatment administration, up to 246 days.)
- Progression-free Survival (PFS)(First treatment administration until tumour progression or death, up to 162 days.)
- Maximum Measured Concentration of the Analyte (BI 836845) in Plasma (Cmax)(Part 1: 5 minutes before and 0.5, 1, 2, 4, 7, 24, 72, 168 and 336 h after infusion for Course 1. Part 2: 5 minutes before and 1, 2, 4, 7, 24, 168, 169, 336, 337 h after infusion for Course 1, 2 and 3.)
- Area Under the Plasma Concentration-time Curve (AUC)(Part 1: 5 minutes before and 0.5, 1, 2, 4, 7, 24, 72, 168 and 336 h after infusion for Course 1. Part 2: 5 minutes before and 1, 2, 4, 7, 24, 168, 169, 336, 337 h after infusion for Course 1, 2 and 3.)
- Time to Maximum Measured Concentration of the Analyte (BI 836845) in Plasma (Tmax)(Part 1: 5 minutes before and 0.5, 1, 2, 4, 7, 24, 72, 168 and 336 h after infusion for Course 1. Part 2: 5 minutes before and 1, 2, 4, 7, 24, 168, 169, 336, 337 h after infusion for Course 1, 2 and 3.)
- Incidence and Intensity of Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)(From first drug administration, until 21 days after last drug administration, up to 253 days.)