PHASE 1/2 STUDY TO EVALUATE PALBOCICLIB (IBRANCE®) IN COMBINATION WITH IRINOTECAN AND TEMOZOLOMIDE OR IN COMBINATION WITH TOPOTECAN AND CYCLOPHOSPHAMIDE IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 128
- 试验地点
- 98
- 主要终点
- Phase 1: Dose Expansion Parts: Frequency of adverse events
研究概览
简要总结
A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors (phase 1). Neuroblastoma tumor specific cohort to further evaluate antitumor activity of palbociclib in combination with topotecan and cyclophosphamide in children, adolescents, and young adults with recurrent or refractory neuroblastoma. Phase 2 to learn about the efficacy of palbociclib in combination with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS).
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
- 2 Years 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
干预措施: Irinotecan (Drug)
Phase 2 Arm A
Palbociclib in combination with irinotecan and temozolomide.
干预措施: Palbociclib (Drug)
Phase 2 Arm A
Palbociclib in combination with irinotecan and temozolomide.
干预措施: Temozolomide (Drug)
Phase 2 Arm A
Palbociclib in combination with irinotecan and temozolomide.
干预措施: Irinotecan (Drug)
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
干预措施: Palbociclib (Drug)
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
干预措施: Temozolomide (Drug)
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
干预措施: Topotecan (Drug)
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
干预措施: Cyclophosphamide (Drug)
Phase 2 Arm B
Irinotecan and temozolomide alone.
干预措施: Temozolomide (Drug)
Phase 2 Arm B
Irinotecan and temozolomide alone.
干预措施: Irinotecan (Drug)
Phase 1 Tumor specific cohort - Neuroblastoma
Palbociclib in combination with topotecan and cyclophosphamide.
干预措施: Palbociclib (Drug)
Phase 1 Tumor specific cohort - Neuroblastoma
Palbociclib in combination with topotecan and cyclophosphamide.
干预措施: Topotecan (Drug)
Phase 1 Tumor specific cohort - Neuroblastoma
Palbociclib in combination with topotecan and cyclophosphamide.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Phase 1: Dose Expansion Parts: Frequency of adverse events
时间窗: At least 28 days after last dose
For Dose Expansion and Tumor-Specific Expansion Parts: Adverse events to be reported during treatment and for at least 28 days after last dose.
Phase 2 open-label, randomized: Event-free survival (EFS) based on Investigator assessment.
时间窗: Baseline to Month 24.
EFS is defined as the time from randomization until first event (ie, progression, recurrence following response, second malignancy or death without progression or recurrence).
Phase 1: First Cycle Dose-Limiting Toxicities (DLT)
时间窗: First cycle (cycle length is approximately 21 days)
For Dose Escalation/Determination Part: DLT defined as any of the following events occurring during the first treatment cycle and considered at least possibly-related to study medication:Grade 4 neutropenia lasting greater than 7 days;Grade 4 thrombocytopenia lasting greater than 7 days or need for platelet transfusion for a platelet count of \< 20,000 per cubic millimeters twice within a 7-day period;greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia;Grade 3 or greater non-hematologic toxicities despite optimal treatment;any Grade 2 or greater non-hematologic toxicity requiring discontinuation or interruption of palbociclib for 7 or more consecutive days during the first cycle or any grade non-hematologic toxicity that delays the start of Cycle 2 by more than 14 days;clinically significant non-hematologic laboratory test abnormality Grade 3 or greater not resolving to Grade 1 or baseline within 7 days.
Phase 1: Dose Expansion Parts: Percentage of Participants With Complete Response or Partial Response
时间窗: Through the end of treatment (up to at least 28 days after last dose)
For Dose Expansion and Tumor-Specific Expansion Parts: patients with confirmed Complete Response or Partial Response per Response Evaluation Criteria in Solid Tumors (RECIST, v.1.1) or modified Response Assessment in Neuro-Oncology (RANO) for central nervous system malignancies, or International Neuroblastoma Response Criteria (INRC) for neuroblastoma, during study treatment, assessed approximately every 2 to 4 cycles (each cycle is approximately 21 days).
次要结局
- Phase 1 and Phase 2: Frequency of adverse events(At least 28 days after last dose)
- Phase 2 open-label, randomized: Event-free survival (EFS) assessed by an independent review committee.(Baseline to Month 24.)
- Phase 1 and Phase 2:Palbociclib Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)(PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.)
- Phase 1 and Phase 2: Percentage of participants with laboratory abnormalities(At least 28 days after last dose)
- Phase 1 and Phase 2: Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings(At least 28 days after last dose)
- Phase 1 and Phase 2: Percentage of Participants With Complete Response or Partial Response(Through the end of treatment (up to at least 28 days after last dose))
- Phase 1 and Phase 2: Progression Free Survival (PFS)(Up to 2 years)
- Phase 2 : comparison of PET-CT response assessment to objective response on CT/MRI.(up to completion of Cycle 4 ( 12 weeks of therapy))
- Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)(PK sampling at time points during Cycle 1 (day 2,5, 6,14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.)
- Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Oral plasma clearance (CL/F)(PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.)
- Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)(PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs(At least 28 days after last dose)
- Phase 1 and Phase 2: Duration of response (DoR) for Participants Who Achieved Complete Response or Partial Response(Up to 2 years)
- Phase 1 and Phase 2: Overall Survival (OS)(Up to 2 years)
- Phase 2: the impact of the combination of palbociclib with TMZ and IRN treatment on the quality of life (QoL) of patients with refractory or recurrent EWS.(Up to Cycle 5 (completion of 12 weeks of treatment))
- Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)(PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Topotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Cyclophosphamide Pharmacokinetics, Oral plasma clearance (CL/F)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Cyclophosphamide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)(PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.)
- Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)(PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Cyclophosphamide Pharmacokinetics, Maximum plasma concentration time (Tmax)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Maximum plasma concentration time (Tmax)(PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.)
- Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum plasma concentration time (Tmax)(PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Oral plasma clearance (CL/F)(PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Irinotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Cyclophosphamide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)
- Phase 1: Cyclophosphamide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)(PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.)