A Phase 1 Study Of Pf-05212384 (Also Known As Pki-587) Administered As An Intravenous Infusion To Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 78
- 试验地点
- 8
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
研究概览
简要总结
This is a two-part study of a compound called PF-05212384 (also known as PKI-587). The purpose of part 1 is to identify the Maximum Tolerated Dose (MTD) of PF-05212384 using a Continual Reassessment Method (CRM). Part 1 will include subjects with any solid tumor. In Part 2 two cohorts will be enrolled. One cohort will assess safety, tolerability and preliminary efficacy in 20 subjects at the MTD and will include subjects with breast cancer, ovarian cancer, endometrial cancer, colorectal cancer renal cancer or glioblastoma (a type of brain tumor). The other cohort will include 5 to 15 subjects with any type of tumor who consent to provide tumor biopsies while participating in the study.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologic diagnosis of any solid tumor
- •Incurable cancer, with disease progression following at least 1 therapy with no further standard treatment available in the opinion of the investigator.
- •At least 1 evaluable lesion per RECIST criteria
排除标准
- •Clinically unstable primary or metastatic CNS tumors
- •Subjects with known diabetes
- •QTc interval greater than 470 ms.
研究组 & 干预措施
1
PF-05212384 (also known as PKI-587)
干预措施: PF-05212384 (also known as PKI-587) (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: Baseline up to Cycle 14 (each cycle is 28 days)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: Baseline up to Cycle 14 (each cycle is 28 days)
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.
Number of Participants With Laboratory Abnormalities
时间窗: Baseline up to Cycle 14 (each cycle is 28 days)
Criteria for laboratory test abnormality: hematology (hemoglobin \[less than {\<} 0.8\*lower limit of normal {LLN}\], platelets \[\<0.5\*LLN or greater than {\>} 1.75\*upper limit of normal {ULN}\], white blood cells \[\<0.6\*LLN or \>1.5\*ULN\], lymphocytes \[\<0.8\*LLN or \>1.2\*ULN\], total neutrophils \[\<0.8\*LLN or \>1.2\*ULN\], basophils, eosinophils, monocytes \[\>1.2\*ULN\]); coagulation \[partial thromboplastin time, prothrombin (PT), PT international ratio \[\>1.1\*ULN\]); liver function (total bilirubin \[\>1.5\*ULN\], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase \[\>0.3\*ULN\], total protein, albumin \[\<0.8\*LLN or \>1.2\*ULN\]).
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Baseline up to Day 28
DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to \[\>=\] grade 3 asthenia \>2 days; or fasting serum glucose \>250 milligrams per deciliter (mg/dL) despite optimal therapy); \>=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment \>2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Recommended Phase-2 Dose (RP2D)
时间窗: Baseline up to Cycle 14 (each cycle is 28 days)
RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose(Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose(Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1)
- Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose(Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1)
- Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose(Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1)
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose(Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1)
- Number of Participants With Maximum Increase From Baseline in Corrected QT Interval(Baseline up to Cycle 14 (each cycle is 28 days))
- Change From Baseline in Serum Glucose at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment(Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14))
- Change From Baseline in Serum Insulin at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment(Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14))
- Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1(Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1)
- Percentage of Participants With Objective Response (OR)(Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days]))
- Change From Baseline in Serum C-peptide at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment(Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14))
- Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22(Baseline, Day 22 of Cycle 1)
- Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue(Baseline)