A Phase I Dose Escalation Trial of Weekly Intravenous Administrations of BI 836845 in Patients With Advanced Solid Cancers 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
- 61
- 试验地点
- 3
- 主要终点
- Part 1: Maximum Tolerated Dose (MTD) 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) or the relevant biological dose (RBD) in the absence if a MTD of a new drug BI 836845 which blocks the insulin-like 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
- 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
Part 1: 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, 8 and 15 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)
Part 1: BI 836845 20 mg
Patients received 20 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 40 mg
Patients received 40 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 60 mg
Patients received 60 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 90 mg
Patients received 90 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 135 mg
Patients received 135 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 200 mg
Patients received 200 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 300 mg
Patients received 300 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 450 mg
Patients received 450 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 600 mg
Patients received 600 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 800 mg
Patients received 800 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 1050 mg
Patients received 1050 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 1400 mg
Patients received 1400 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 1: BI 836845 1800 mg
Patients received 1800 mg of BI 836845 (concentrate for solution for infusion) given intravenously for 1 hour on Day 1, 8 and 15 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)
Part 2: Ewing's sarcoma family of tumours
Patients with Ewing's sarcoma family of tumours (ESFT) 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)
Part 2: 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
Part 1: Maximum Tolerated Dose (MTD) 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
In the absence of MTD, the relevant biological dose (RBD) of BI 836845 during the first treatment course of the dose escalation phase was reported. The MTD was defined as the highest dose level of BI 836845 at which no more than 1 out of 6 patients experienced a drug related dose limiting toxicity (DLT) during the first course of treatment. Starting dose of 10 milligrams (mg) BI 836845, administered thrice every 3 weeks. Dose levels evaluated were: 10 mg, 20 mg, 40 mg, 60 mg, 90 mg, 135 mg, 200 mg, 300 mg, 450 mg, 600 mg, 800 mg, 1050 mg, 1400 mg and 1800 mg. The BI 836845 dose which could achieve a plateau in total Insulin-like growth factor 1 (IGF-1) plasma concentrations was considered the RBD.
Part 1: Number of Patients With Dose Limiting Toxicities (DLTs) During the Maximum Tolerated Dose (MTD) Evaluation Period
时间窗: During the first course of treatment, up to 21 days
Number of participants with DLTs occurring during the first treatment course of the dose escalation part. DLT was defined as drug-related adverse events meeting the criteria summarized below: * Common terminology criteria for adverse events (CTCAE) grade 4 neutropenia for ≥ 7 days (d) * Febrile neutropenia with single temperature of \> 38.3°C/ ≥ 38°C more than 1 hour (h) * Documented infection with high neutrophile count * CTCAE grade 4 thrombocytopenia/CTCAE grade 3 thrombocytopenia associated with bleeding requiring transfusion * AST (Aspartate Amino Transferase)/ALT (Alanine Amino Transferase) \> 5x normal * CTCAE grade 3/4 non-hematologic toxicity * CTCAE grade ≥2 infusion reaction * CTCAE grade ≥2 nausea and/or vomiting for ≥7 d * CTCAE grade ≥3 skin toxicity * CTCAE grade ≥3 hyperglycemia * Any electrolyte grade 3 AE * No recovery from non-DLT CTCAE grade \>2 * Sustained fatigue/asthenia grade 3 for longer than 96 h * Other event qualified as DLT by the investigator
次要结局
- Objective Tumour Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1(First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.)
- Duration of Objective Response(First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.)
- Best Overall Response Based on Response Evaluation Criteria In Solid Tumours (RECIST) Criteria Version 1.1(First treatment administration until disease progression or last evaluable assessment in absence of progression; Up to 72 weeks)
- Disease Control(First treatment administration until the earliest of disease progression, death, last adequate tumor assessment or the start of subsequent anti-cancer therapy. Up to 72 weeks.)
- Part 2 - Biopsiable Tumours: Progression-free Survival (PFS)(First treatment administration until tumour progression or death. Up to 72 weeks)
- Maximum Measured Concentration of the BI 836845 in Plasma (Cmax)(Up to 337 hours. Detailed timeframe is in the description.)
- Time to Maximum Measured Concentration BI 836845 in Plasma (Tmax)(Up to 337 hours. Detailed timeframe is in the description.)
- Area Under the Plasma Concentration-time Curve of BI 836845 From Time 0 to 168 Hours (AUC 0-168)(Up to 337 hours. Detailed timeframe is in the description.)
- Incidence and Intensity of Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)(First treatment administration until end of treatment plus residual effect period; Up to 74 weeks)