Phase I Dose-Escalation Study Of Oral SKI-606 In Subjects With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
研究概览
简要总结
To evaluate the safety and tolerability of oral SKI-606 (bosutinib) administered on a daily schedule to subjects with advanced malignant solid tumors and to define a maximum tolerated dose (MTD) in this subject population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Advanced or recurrent solid malignancy confirmed histologically or cytologically for which no effective therapy is available.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 -
- •Measurable disease as outlined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
- •Other inclusion applies.
排除标准
- •Use of any systemic antitumor agents or any investigational agent within 28 days before the first dose of test article is administered.
- •Prior exposure to SKI-606 or any other Src-kinase inhibitor, major surgery or radiotherapy within 14 days before the first dose of test article (recovery from previous surgery should be complete before day 1).
- •Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth (Treated CNS metastases must be stable for >= 2 weeks before day 1).
- •Other exclusion applies.
研究组 & 干预措施
Dose escalation
Dose finding study of monotherapy bosutinib in patients with advanced solid tumors.
干预措施: bosutinib (Drug)
Colorectal Cancer
Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.
干预措施: bosutinib (Drug)
Pancreatic Cancer
Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.
干预措施: bosutinib (Drug)
Non-Small Cell Lung Cancer (NSCLC)
Enroll 30 patients at RP2D to further evaluate safety and efficacy in subgroup population.
干预措施: bosutinib (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
时间窗: Part 1 Baseline up to Day 28
DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (\>=) 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to less than or equal to \[=\<\] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
Number of Participants With Adverse Events (AEs) by Seriousness
时间窗: Baseline up to 30 days after last dose
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category.
Duration of Most Frequently Observed Adverse Events (AEs)
时间窗: Baseline up to 30 days after last dose
The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1.
Number of Participants With Best Overall Response (BOR) in Part 1
时间窗: Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):\>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Number of Participants With Best Overall Response (BOR) in Part 2
时间窗: Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: \>=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: \>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Maximum Tolerated Dose (MTD) in Part 1
时间窗: Part 1 Day 1 up to Day 28
MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of \>= 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to =\< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
次要结局
- Maximum Tolerated Dose (MTD) for Prolonged Use(Part 1 Day 1 up to Day 28)
- Number of Participants With Change From Baseline in Laboratory Test Results(Baseline up to end of treatment (Week 95))
- Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray(Baseline up to end of treatment (Week 95))
- Concomitant Medications Used for Management of Adverse Events (AEs)(Day 1 up to end of treatment (Week 95))
- Change From Baseline in Karnofsky Performance Score(Baseline up to end of treatment (Week 95))
- Number of Participants With Change From Baseline in Physical Examination(Baseline up to end of treatment (Week 95))
- Number of Participants With Change From Baseline in Opthalmologic Examination(Baseline up to end of treatment (Week 95))
- Overall Survival (OS) in Part 2(Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation)
- Progression Free Survival (PFS) in Part 2(Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation)
- Maximum Observed Plasma Concentration (Cmax)(0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14)
- Plasma Decay Half-Life (t1/2)(0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14)
- Area Under the Concentration-Time Curve (AUC)(0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14)