An Open Label, Phase Ia/Ib Dose Finding Study With BI 894999 Orally Administered Once a Day in Patients With Advanced Malignancies, 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
- 174
- 试验地点
- 16
- 主要终点
- Phase Ia: Number of Patients With DLTs Observed in the First Cycle
研究概览
简要总结
This study is open to adults with different types of advanced cancer (solid tumours). The study is also open to patients with diffuse large B-cell lymphoma in whom previous treatment was not successful. In some countries, adolescents who are at least 15 years old and who are diagnosed with NUT carcinoma can also participate. No standard treatment exists for this rare and aggressive form of cancer.
The purpose of this study is to find out the highest dose of BI 894999 that people can tolerate.
BI 894999 is tested for the first time in humans. Participants take tablets once daily. The study also tests whether participants can tolerate BI 894999 better when taken continuously or with breaks in between.
Participants can stay in the study as long as they benefit from the treatment and can tolerate it.
The doctors also regularly check the general health of the participants.
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
Phase Ia - Schedule A: 0.2 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule A: 0.5 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule A: 1 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule A: 1.5 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule A: 2 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule A: 5 mg BI 894999
Once daily continuous oral intake in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 1.5 mg BI 894999
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 2 mg BI 894999
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 2.5 mg BI 894999
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule C: 5/2.5 mg BI 894999
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule C: 6/3 mg BI 894999
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule C: 7/3.5 mg BI 894999
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)
Once daily intermittent oral intake with two weeks on treatment followed by one week off in 3-week cycles.
干预措施: BI 894999 (Drug)
Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Once daily loading dose on Day 1 followed by six days daily intake of maintenance dose, followed by one week off, repeated every two weeks in cycles of 28 days.
干预措施: BI 894999 (Drug)
结局指标
主要结局
Phase Ia: Number of Patients With DLTs Observed in the First Cycle
时间窗: First treatment cycle (the first 21 days for Schedules A and B, the first 28 days for Schedule C).
Number of patients with Dose Limiting Toxicities (DLTs) observed in the first treatment cycle of Phase Ia is reported. The following drug related adverse events (AEs) qualified as DLT: * any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: * inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades * electrolytes abnormalities that were corrected within 72 hours with treatment * any haematologic AE related to the trial medication defined as follows: * CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or * CTCAE grade ≥4 thrombocytopenia, or * CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or * febrile neutropenia CTCAE grade 3 or higher. * any other drug-related AE preventing the patient from taking his treatment according to the given schedule.
Phase Ib: Number of Patients With DLTs Observed During the On-treatment Period
时间窗: Date of the first administration of study treatment until date of the last administration of study treatment + 30 days residual effect period, up to 883 days.
Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period of Phase Ib is reported. The following drug related adverse events (AEs) qualified as DLT: * any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: * inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades * electrolytes abnormalities that were corrected within 72 hours with treatment * any haematologic AE related to the trial medication defined as follows: * CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or * CTCAE grade ≥4 thrombocytopenia, or * CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or * febrile neutropenia CTCAE grade 3 or higher. * any other drug-related AE preventing the patient from taking his treatment according to the given schedule.
次要结局
- Phase Ia: Number of Patients With DLTs Observed During the On-treatment Period(Date of the first administration of study treatment until date of the last administration of study treatment + 30 days residual effect period, up to 463 days.)
- Phase Ia and Phase Ib: Maximum Measured Concentration of BI 894999 in Plasma After the First Dose (Cmax)(5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h and 23h55min after administration of first BI 894999 dose on Day 1 of Cycle 1.)
- Phase Ia and Phase Ib: Area Under the Concentration-time Curve of BI 894999 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ, ss)(5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, and at 23h55min (Schedule A) or 24h (Schedule B & C) following administration on day 14 (Schedule A & B) or day 21 (Schedule C).)
- Phase Ia and Phase Ib: Objective Response (OR)(Up to 15 months for Phase 1a and up to 28 months for Phase Ib.)
- Phase Ib: Progression-free Survival or (PFS) or Radiological PFS for mCRPC Patients With Non-measurable Disease by RECIST v1.1(Up to 28 months.)
- Phase Ia and Phase Ib: Area Under the Concentration-time Curve of BI 894999 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)(5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h and 23h55min after administration of first BI 894999 dose on Day 1 of Cycle 1.)
- Phase Ia and Phase Ib: Maximum Measured Concentration of BI 894999 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax, ss)(5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, and at 23h55min (Schedule A) or 24h (Schedule B & C) following administration on day 14 (Schedule A & B) or day 21 (Schedule C).)
- Phase Ib: Best Overall Response(Imaging and assessment performed every 2 cycles (solid tumours patients) or 4 cycles (mCRPC patients) for the entire treatment period, up to 28 months.)
- Phase Ib: Overall Survival(Up to 28 months.)
- Phase Ib: Prostate Specific Antigen (PSA) Response in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)(Up to 93 days.)