A Phase 1 Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Cyclin-Dependent Kinase (CDK) Inhibitor SCH 727965 Administered Every 3 Weeks in Subjects With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 81
- 主要终点
- Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity
研究概览
简要总结
Part 1 and Part 2 of this trial will evaluate the safety, tolerability, maximum administered dose, and dose limiting toxicity of SCH 727965 administered every 3 weeks as a 2 hour intravenous (IV) infusion (Part 1), and as an 8-hour or 24-hour IV infusion (Part 2). Each 3-week period is considered one treatment cycle. Part 3 of this trial will evaluate the effect of coadministration of antiemetic drug aprepitant on the pharmacokinetics of SCH 727965 administered as a 2 hour IV infusion once every 3 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Age >=18 years, either sex, any race.
- •Subjects must have histologically proven solid tumors, non-Hodgkin's lymphoma, or multiple myeloma.
- •There must be no known standard therapy, or disease must be refractory to standard therapy.
- •Eastern Cooperative Oncology Group performance status of 0, 1, or
- •Adequate hematologic, renal, and hepatic organ function and laboratory parameters.
排除标准
- •Symptomatic brain metastases or primary central nervous system malignancy.
- •Previous radiation therapy to >25% of the total bone marrow.
- •Previous treatment with SCH
- •Known HIV infection.
研究组 & 干预措施
2 Hour SCH 727965 infusion
Participants treated with 2 hour SCH 727965 IV infusion
干预措施: SCH 727965 (Drug)
8 Hour SCH 727965 infusion
Participants treated with 8 hour SCH 727965 IV infusion.
干预措施: SCH 727965 (Drug)
24 Hour SCH 727965 infusion
Participants treated with 24 hour SCH 727965 IV infusion.
干预措施: SCH 727965 (Drug)
2 Hour SCH 727965 infusions plus aprepitant in Cycle 1
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 1 only.
干预措施: SCH 727965 (Drug)
2 Hour SCH 727965 infusions plus aprepitant in Cycle 1
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 1 only.
干预措施: Aprepitant (Drug)
2 Hour SCH 727965 infusions plus aprepitant in Cycle 1
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 1 only.
干预措施: Ondansetron (Drug)
2 Hour SCH 727965 infusions plus aprepitant in Cycle 1
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 1 only.
干预措施: Dexamethasone (Drug)
2 Hour SCH 727965 infusion plus aprepitant in Cycle 2
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 2 only.
干预措施: SCH 727965 (Drug)
2 Hour SCH 727965 infusion plus aprepitant in Cycle 2
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 2 only.
干预措施: Aprepitant (Drug)
2 Hour SCH 727965 infusion plus aprepitant in Cycle 2
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 2 only.
干预措施: Ondansetron (Drug)
2 Hour SCH 727965 infusion plus aprepitant in Cycle 2
Participants randomized to 2 Hour SCH 727965 infusion, plus concomitant ondansetron and dexamethasone in Cycles 1 and 2, and aprepitant in Cycle 2 only.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Safety and tolerability of SCH 727965, including maximum administered dose and dose-limiting toxicity
时间窗: End of trial
In Part 1 and Part 2, pharmacodynamic effects of SCH 727965 with an ex vivo lymphocyte stimulation assay of participant's peripheral blood lymphocytes.
时间窗: Cycle 1
次要结局
- In Part 3, area under the plasma concentration versus time curve and maximum concentration of SCH 727965 administered as a 2 hour intravenous infusion with or without aprepitant in participants with advanced malignancies.(Cycle 1 Days 1 and 2, and Cycle 2 Days 1 and 2)