An Open-Label Phase IB Trial To Evaluate the Effects of Food and Formulation on Pharmacokinetics of the Oral Selective Inhibitor of Nuclear Export/SINE Compound KPT-330 in Patients With Soft-Tissue or Bone Sarcoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 2
- 主要终点
- Time of First Maximum Observed Concentration (Tmax) of Selinexor
研究概览
简要总结
The purpose of this research study is to find out more information such as: to determine the effects of high and low fat foods on the pharmacokinetics (PK) of oral KPT-330 tablets and to compare PK of capsules and tablets in Arms 1 and 2; to evaluate tumor response in sarcoma participants in Arm 3; to compare the PK of 60 milligrams (mg) of the new, 2nd generation tablet formulation and 60 mg of the selinexor suspension formula to the current, 1st generation tablets.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Patients must have histologically confirmed soft tissue or bone/cartilage sarcoma. Patients with sarcoma of small round blue cell tumor types are allowed. Gastrointestinal stromal tumors (GIST) are excluded.
- •Patients must have received at least one prior anticancer regimen for metastatic disease unless there is no other therapy available and evidence of progressive disease on study entry. Patients with stable disease will be included if there has been failure to respond to another drug(s) within the previous 3 months
排除标准
- •Patients with known liver metastases
- •Radiation, chemotherapy, immunotherapy, any other systemic anticancer therapy or participation in an investigational anti-cancer study ≤ 3 weeks prior to initiation of therapy
- •Patients with known brain metastasis
- •Patients with any gastrointestinal dysfunctions that could interfere with the interpretation of the food effect data
- •Patients with known intolerance to low or high fat meals
- •In the opinion of the investigator, patients who are significantly below their ideal body weight
研究组 & 干预措施
Arm 1
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 milligrams per meter square (mg/m^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).
干预措施: KCP-330 (Drug)
Arm 2
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.
干预措施: KCP-330 (Drug)
Arm 3
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 50 mg/m^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption.
干预措施: KCP-330 (Drug)
Arm 4
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence ABC (Treatment A: current [1st generation] tablets on Day 1 of Week 1; Treatment B: new [2nd generation] tablets on Day 1 of Week 2; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.
干预措施: KCP-330 (Drug)
Arm 5
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence CAB (Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 1; Treatment A: current [1st generation] tablets on Day 1 of Week 2; Treatment B: new [2nd generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.
干预措施: KCP-330 (Drug)
Arm 6
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence BCA (Treatment B: new [2nd generation] tablets on Day 1 of Week 1; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 2; Treatment A: current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1.
干预措施: KCP-330 (Drug)
结局指标
主要结局
Time of First Maximum Observed Concentration (Tmax) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data.
Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18, 24, and 48 hours post-dose
AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration.
Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), AUC0-inf was calculated as AUC0-t + Ct/ elimination rate constant (kel), where: Ct = the last observed non- zero concentration.
Maximum Observed Plasma Concentration (Cmax) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data.
Terminal Phase Half-Life (t1/2) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
t1/2 was the terminal phase half-life, it was calculated as ln(2)/kel.
Apparent Total Body Clearance (CL/F) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram \[kg\]).
Apparent Volume of Distribution (Vd/F) of Selinexor
时间窗: Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose
Vd/F was calculated as Dose/ (kel \*AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg).
次要结局
- Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria(From the date of first documented response until the date of documented progression or last disease assessment (up to 39 months))
- Duration of Stable Disease as Per RECIST v1.1 Criteria(From the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression, censored date (up to 39 months))
- Progression Free Survival (PFS) as Per RECIST v1.1 Criteria(From first dose of study treatment to time of disease progression or death, censored date (up to 39 months))
- Overall Survival (OS)(From first dose of study treatment to death, censored date (up to 39 months))
- Time to Progression (TTP)(From first dose of study treatment to first documented evidence of disease recurrence or progression, or death, censored date (up to 39 months))
- Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33(Up to 39 months)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs(From screening up to 30 days post last study drug dose (up to 39 months))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity(From screening up to 30 days post last study drug dose (up to 39 months))
- Number of Participants With Clinically Significant Laboratory Abnormalities(From screening up to 30 days post last study drug dose (up to 39 months))
- Number of Participants With Clinically Significant Changes in Vital Signs(From screening up to 30 days post last study drug dose (up to 39 months))
- Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs)(From screening up to 30 days post last study drug dose)