A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
研究概览
简要总结
The purpose of this study is to assess the effect of multiple-dose administration of rifampin on the single dose PK of pevonedistat in adult participants with advanced solid tumors.
详细描述
The study will enroll approximately 20 participants. The study will be conducted in two Parts: Part A and optional Part B. Part A will have a drug-drug interaction (DDI) assessment. In Part A, participants will be assigned to:
• Pevonedistat 50 mg/m^2 + Rifampin
Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC chemotherapy, docetaxel or carboplatin plus paclitaxel. The investigator will decide which SoC combination partner a participant will receive.
- Pevonedistat 25 mg/m^2 + Docetaxel
- Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel
This multi-center trial will be conducted in the United States. The overall time to participate in this study is 18 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug or before the start of subsequent therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 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
- •Adult participants who have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that is appropriate for treatment with either docetaxel or carboplatin + paclitaxel in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Expected survival of at least 3 months from the date of enrollment in the study.
- •Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the effects of prior antineoplastic therapy.
- •Adequate organ functions (kidney, liver, cardiac, bone marrow).
- •Suitable venous access for the study-required blood sampling (including PK sampling).
排除标准
- •Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.
- •Life-threatening illness or serious (acute or chronic) medical or psychiatric illness unrelated to cancer.
- •Active, uncontrolled infection or severe infectious disease.
- •Known human immunodeficiency virus (HIV) seropositive or known hepatitis B or hepatitis C infection.
- •With significant heart or pulmonary disease.
- •Requiring chronic treatment with breast cancer resistance protein (BCRP) inhibitors.
- •Criteria for Continuation into Optional Part B:
- •To be eligible for Part B, participants must have completed Part A and be reassessed to determine if they meet the continuation criteria for Part B.
研究组 & 干预措施
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg
Pevonedistat 50 milligram per square meter (mg/m^2), intravenous infusion, once on Day 1 and 10 along with rifampin 600 milligram (mg), capsule, orally, once daily from Day 3 up to Day 11 in Part A. After completion of Part A, participants had opportunity to continue into optional Part B.
干预措施: Pevonedistat (Drug)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg
Pevonedistat 50 milligram per square meter (mg/m^2), intravenous infusion, once on Day 1 and 10 along with rifampin 600 milligram (mg), capsule, orally, once daily from Day 3 up to Day 11 in Part A. After completion of Part A, participants had opportunity to continue into optional Part B.
干预措施: Rifampin (Drug)
Part B: Pevonedistat
Pevonedistat 25 mg/m^2 intravenously in combination with docetaxel 75 mg/m^2 or at 20 mg/m^2 in combination with carboplatin +paclitaxel 175 mg/m^2; pevonedistat was given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants were treated for up to 12 cycles or symptomatic deterioration or PD, treatment was discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) was based on investigator discretion. If the sponsor and investigator determine that a participant would derive clinical benefit from continued treatment, the participant may remain on the current combination therapy or receive pevonedistat as a single agent beyond 12 cycles.
干预措施: Pevonedistat (Drug)
Part B: Pevonedistat
Pevonedistat 25 mg/m^2 intravenously in combination with docetaxel 75 mg/m^2 or at 20 mg/m^2 in combination with carboplatin +paclitaxel 175 mg/m^2; pevonedistat was given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants were treated for up to 12 cycles or symptomatic deterioration or PD, treatment was discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) was based on investigator discretion. If the sponsor and investigator determine that a participant would derive clinical benefit from continued treatment, the participant may remain on the current combination therapy or receive pevonedistat as a single agent beyond 12 cycles.
干预措施: Docetaxel (Drug)
Part B: Pevonedistat
Pevonedistat 25 mg/m^2 intravenously in combination with docetaxel 75 mg/m^2 or at 20 mg/m^2 in combination with carboplatin +paclitaxel 175 mg/m^2; pevonedistat was given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants were treated for up to 12 cycles or symptomatic deterioration or PD, treatment was discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) was based on investigator discretion. If the sponsor and investigator determine that a participant would derive clinical benefit from continued treatment, the participant may remain on the current combination therapy or receive pevonedistat as a single agent beyond 12 cycles.
干预措施: Carboplatin (Drug)
Part B: Pevonedistat
Pevonedistat 25 mg/m^2 intravenously in combination with docetaxel 75 mg/m^2 or at 20 mg/m^2 in combination with carboplatin +paclitaxel 175 mg/m^2; pevonedistat was given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants were treated for up to 12 cycles or symptomatic deterioration or PD, treatment was discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) was based on investigator discretion. If the sponsor and investigator determine that a participant would derive clinical benefit from continued treatment, the participant may remain on the current combination therapy or receive pevonedistat as a single agent beyond 12 cycles.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
时间窗: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
The Least square (LS) means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
时间窗: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
时间窗: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.
次要结局
- Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)(Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose)
- Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)(Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose)
- Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)(Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose)
- Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment(Up to Cycle 17 (end of treatment) (Cycle length =21 days))