A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06840003 IN PATIENTS WITH MALIGNANT GLIOMAS
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 17
- 试验地点
- 13
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
研究概览
简要总结
This study will evaluate the safety and tolerability of increasing doses of PF-06840003 in patients with malignant gliomas.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosis of WHO Grade IV glioblastoma or WHO Grade III anaplastic gliomas
- •For patients with Grade IV GBM, recurrent disease at the time of the first or second recurrence or progression. For patients with Grade III anaplastic gliomas, recurrent disease at the time of at least a first recurrence but no more than a fourth recurrence or progression
- •Karnofsky performance score greater than or equal to 70%
- •Adequate bone marrow, kidney and liver function
排除标准
- •History of CNS bleeding within 6 months of registration
- •Previous anti-angiogenics or anti-vascular endothelial growth factor within 12 months of registration
- •Requires treatment with high dose systemic corticosteroids defined as >2 mg/day
- •Radiation therapy within 12 weeks of registration
研究组 & 干预措施
PF-06840003
Daily Oral PF-06840003
干预措施: PF-06840003 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs) [Part 1]
时间窗: Baseline to Day 28
DLTs: Any of the following adverse events (AE) occurring in the first cycle of treatment, unless there is a clear alternative explanation. Hematologic: Grade (Gr) 4 neutropenia lasting \>=5 days; febrile neutropenia; Gr\>=3 neutropenic with infection; Gr\>=3 thrombocytopenia with bleeding; Gr 4 thrombocytopenia. Non-Hematologic: Any toxicity attributable to PF-06840003 that resulted in administration of less than 80% of the planned doses during Cycle 1; Gr 4 non-hematologic AE; Gr 3 AE lasting \>7 days despite optimal supportive care; Gr 3 central nervous system (CNS) AE regardless of duration; Gr 3 QTc prolongation (QTc \>500 milliseconds) (a DLT only if persisting after correction of any reversible causes); Concurrent aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3\*upper limit of normal (ULN) and total bilirubin \>2\*ULN.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Part 1]
时间窗: Baseline up to 1 year
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Number of Participants With TEAEs by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1]
时间窗: Baseline up to 1 year
Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
次要结局
- Steady-State Trough Level Ratio [Part 1](Baseline and Day 15)
- Objective Response Rate (ORR) [Part 1](Weeks 8, 16, and 24)
- Disease Control Rate (DCR) Based on the Immunotherapy Response Assessment for Neuro-Oncology (iRANO) Criteria [Part 1](Weeks 8, 16, and 24)
- Number of Participants With Hematology Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1](Baseline up to 1 year)
- Number of Participants With Clinically Significant Findings in Vital Signs [Part 1](Baseline up to 1 year)
- Number of Participants With Chemistries Laboratory Abnormalities by Severity (as Graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Event [CTCAE] Version 4.03) [Part 1](Baseline up to 1 year)
- Single Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Single Dose: Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Multiple Dose: Maximum Observed Plasma Concentration (Cmax) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 1 pre-dose, 1, 2, 4, 6, 8, 24 and 72 hours post Cycle 1 Day 1 dose)
- Multiple Dose: Terminal Half-Life (t1/2) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Lowest Concentration Observed During the Dosing Interval (Cmin) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Average Concentration for the Dosing Interval (Cav) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Apparent Clearance (CL/F) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Apparent Volume of Distribution (Vz/F) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Observed Accumulation Ratio (Rac) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Multiple Dose: Steady State Accumulation Ratio (Rss) of PF-06840002 and PF-06840001 [Part 1](Cycle 1 Day 15 pre-dose, 1, 2, 4, 6, 8, 24 hrs post)
- Plasma Kynurenine and Tryptophan [Part 1](Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose)
- Plasma Endogenous Kynurenine/Tryptophan Ratio [Part 1](Cycle 1 Day 1 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose; Cycle 1 Day 4 and Day 8 pre-dose; Cycle 1 Day 15 pre-dose, and 1, 2, 4, 6, 8, 24 hours post-dose)