A Non-randomized, Open-label, Multi-center, Phase I/II Study of Phosphatidylinositol-3-kinase (PI3K) Inhibitor Copanlisib in Pediatric Patients With Relapsed/Refractory Solid Tumors or Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Bayer
- 入组人数
- 31
- 试验地点
- 14
- 主要终点
- Phase 1: Number of Subjects With Dose Limiting Toxicity (DLT)
研究概览
简要总结
This study is designed to investigate whether the use of copanlisib is safe, feasible and beneficial to pediatric patients with solid solid tumors or lymphoma that are recurrent or refractory to standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form by patients and/or patients' parents/legal guardians and age appropriate assent form by the patients obtained before any study specific procedure
- •Male or female patients from 6 months to ≤ 21 years old at the time of study enrollment
- •Confirmation of diagnosis:
- •Phase I: Patients must have histologic verification of a solid tumor or lymphoma malignancy at diagnosis, with measurable or evaluable disease, for which there is no standard curative anti-cancer treatment or treatment is no longer effective and must have received ≥ 1 prior line of therapy.
- •Phase II: patients must have histologically verified tumor at initial diagnosis and radiologically or histologically confirmed status at inclusion as indicated in the following: neuroblastoma, osteosarcoma, rhabdomyosarcoma or Ewing sarcoma.
- •Patients with solid tumors must have measurable disease (evaluable disease is acceptable for neuroblastoma and Ewing sarcoma). Tumor assessment will be done via computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT). Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion. Bone scans (if clinically indicated) should be obtained within ≤ 4 weeks prior to the start of treatment.
- •Performance level: Lansky ≥ 50% for patients ≤ 16 years of age and Karnofsky ≥ 50% for patients > 16 years of age.
- •Adequate bone marrow, renal and liver function.
排除标准
- •Active or uncontrolled infection (National Cancer Institute (NCI)-CTCAE Grade ≥ 2).
- •History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
- •Diabetes mellitus.
- •Uncontrolled arterial hypertension despite optimal medical management (per institutional guidelines).
- •Patients with central nervous system (CNS) malignancies.
研究组 & 干预措施
Dose escalation of BAY806946 in Phase 1
It is estimated that 2 or 3 dose cohorts may be evaluated in phase 1 of the study. Safety and MTD/RP2D dose will be evaluated in 2 age groups (< 1 year old and ≥ 1 year old).
干预措施: Copanlisib (BAY806946) (Drug)
Patients with Neuroblastoma in Phase 2
Recommended Phase 2 dose (RP2D) for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
干预措施: Copanlisib (BAY806946) (Drug)
Patients with Osteosarcoma in Phase 2
RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
干预措施: Copanlisib (BAY806946) (Drug)
Patients with Rhabdomyosarcoma in Phase 2
RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
干预措施: Copanlisib (BAY806946) (Drug)
Patients with Ewing sarcoma in Phase 2
RP2D for copanlisib in pediatric patients, as defined in the Phase I part of the study, will be used.
干预措施: Copanlisib (BAY806946) (Drug)
结局指标
主要结局
Phase 1: Number of Subjects With Dose Limiting Toxicity (DLT)
时间窗: Cycle 1 (28 days)
DLT was observed during first cycle of treatment, and assessed as possibly, probably or definitely related to treatment with copanlisib. The DLT observation period for the purposes of dose-escalation was the first cycle of therapy.
Phase 2: Objective Response Rate (ORR)
时间窗: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
ORR was defined separately in each indication, as the number of responders divided by the number of subjects in FAS in the indication.
Phase 2: Disease Control Rate (DCR)
时间窗: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
The DCR was defined as the number of subjects with disease control divided by the number of subjects in FAS or per protocol set (PPS) in the indication.
Phase 2: Progression-free Survival (PFS)
时间窗: Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.
Phase 1: Number of Subjects With Serious Adverse Events (SAEs)
时间窗: Up to 150 days.
This endpoint was performed on SAF.
Phase 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
时间窗: After the first study intervention up to 30 days after the last dose of the study drug intake (end of safety follow up), with a maximum of 145 days.
TEAE was defined as any event arising or worsening after start of study drug administration until 30 days after the last dose of the study drug intake (end of safety follow-up). This endpoint was performed on SAF.
Phase 1: Number of Participants With Treatment-related Adverse Events (AEs).
时间窗: Up to 145 days.
This endpoint was performed on SAF.
Phase 1: The Maximum Tolerated Dose (MTD): the Highest Dose Level of Copanlisib That Can be Given so That Not More Than 1 Out of 6 Patients Experience a DLT During the DLT Evaluation Period.
时间窗: Cycle 1 (28 days)
Maximum tolerated dose (MTD) for copanlisib was defined as the highest dose level where 6 patients have been treated and ≤ 1 participant experienced a DLT. This endpoint was performed on SAF.
次要结局
- Phase 2: Overall Survival (OS)(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)
- Phase 2: Number of Subjects With Treatment Emergent SAEs(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)
- Phase 2: PFS in Each Indication Except for Osteosarcoma(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)
- Phase 2: Number of Subjects With Treatment-emergent Clinically Significant Change in Laboratory Parameters, ECGs and Vital Signs(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)
- Phase 1: Area Under the Curve (AUC(0-168))(Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25 hour (h), 1.5- 3h, 22-24h). Age < 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25h, 22-24h). Cycle length is 28 days.)
- Phase 2: Number of Participants With Treatment-emergent AEs(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)
- Phase 1: Copanlisib Maximum Drug Concentration (Cmax)(Age ≥ 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25 hour (h), 1.5- 3h, 22-24h). Age < 6 years: Pre-dose, Post-dose on Cycle 1 Day 1 and Day 15 (1-1.25h, 22-24h). Cycle length is 28 days.)
- Phase 1: Objective Response Rate (ORR)(Up to 150 days)
- Phase 2: Duration of Response (DOR)(Data was not collected for this endpoint due to study was terminated before the initiation of phase 2.)