NCT05081180终止1 期
Single-arm, Multicenter Phase I/Ib Study of Avelumab + Lenvatinib in Children With Primary CNS Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 10
- 主要终点
- Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This study consists of 2 parts: Dose Escalation Part 1 and Dose Expansion Part 2. The Dose Escalation Part 1 will evaluate the safety and tolerability of Avelumab in combination with Lenvatinib and determine the recommended Avelumab and Lenvatinib dose for expansion. Dose Expansion Part 2 will assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary central nervous system (CNS) tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with histologically confirmed diagnosis of primary CNS malignancy as follows: a) Primary CNS tumors: the tumor should be considered high-grade histologically; prior radiotherapy is allowed; participants must have progressed after at least 1 prior systemic therapy, except for those with diffuse midline glioma with or without the H3 K27M mutation. b) Specific for participants with diffuse midline glioma with or without the H3 K27M mutation: prior radiotherapy is allowed; no more than 1 prior systemic therapy is allowed; participants with diffuse midline glioma with or without the H3 K27M mutation who have not received prior systemic therapy but have prior radiotherapy only are allowed to enroll
- •On screening scans, measurable disease by RANO criteria
- •Participants must have a Lansky performance status >= 50 for age <= 16 years or Karnofsky performance status >= 50 for age > 16 years at Screening
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants with low-grade gliomas, for example but not limited to, subependymal giant cell astrocytoma, pilocytic astrocytoma and World Health organization (WHO) Grade 1 tumors
- •Participants demonstrating evidence of worsening of neurologic deficit within 1 week prior to initiation of study interventions
- •Participants with bulky tumor, defined as: a) Tumor with any evidence of uncal herniation or midline shift; b) Tumor with a diameter of > 4 centimeters (cm) in 1 dimension on T2/ fluid-attenuated inversion recovery (FLAIR) images; c) Tumor that in the opinion of the Investigator shows significant mass effect
- •Participants are not eligible if they experience uncontrolled seizures, defined as: a) Seizures requiring regular use of rescue medications. b) Seizures requiring increasing doses of antiepileptic medications. c) Seizures that in the opinion of the Investigator compromise the ability of the participant to tolerate study intervention or interfere with study procedures
- •Participants who have received major surgery (including but not limited to neurosurgical resection, brain biopsy, or radiation to the primary brain tumor) within 28 days prior to the first dose of study interventions
- •Participants with history of intracranial hemorrhage/spinal cord hemorrhage within 28 days prior to the first dose of study interventions
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
Avelumab + Lenvatinib
Experimental
干预措施: Avelumab (Drug)
Avelumab + Lenvatinib
Experimental
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Dose Escalation Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: Baseline (Day 1) up to Day 28
Dose Escalation Part 1: Number of Participants with Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater Than or Equal to (>=) 3 Treatment-emergent Adverse Event (TEAEs) According to National Cancer Institute-CTCAE Version 5.0
时间窗: up to 857 days
Dose Expansion Part 2: Progression-free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators
时间窗: until progressive disease or death, assessed up to Day 1534
次要结局
- Dose Expansion Part 2:Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab(Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534)
- Dose Escalation Part 1: Number of Participants with Clinically Significant Changes from Baseline in Laboratory Parameters(up to 876 days)
- Dose Escalation Part 1: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators(up to 876 days)
- Dose Escalation Part 1: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab(Pre-dose up to 30 days after last dose, assessed up to approximately 876 days)
- Dose Escalation Part 1: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib(Pre-dose up to 30 days after last dose, assessed up to approximately 876 days)
- Dose Escalation Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib(Pre-dose up to 30 days after last dose, assessed up to approximately 876 days)
- Dose Escalation Part 1: Immunogenicity of Avelumab as Measured by Antidrug Antibody (ADA) Assay(up to 876 days)
- Dose Escalation Part 1: Objective Response Rate (ORR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators(up to 876 days)
- Dose Escalation Part 1: Progression-Free Survival (PFS) According to Response Assessment in Neuro-Oncology (RANO) Criteria(until progressive disease or death, assessed up to 876 days)
- Dose Escalation Part 1: Overall Survival (OS)(up to 876 days)
- Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths(up to 876 days)
- Dose Escalation Part 1: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0(up to 876 days)
- Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (AEs) Based on Severity According to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0(up to Day 1534)
- Dose Expansion Part 2: Number of Participants with Clinically Significant Changes in Laboratory Parameters(up to Day 1534)
- Dose Expansion Part 2: Serum Observed Concentration at End of Infusion (CEOI) of Avelumab(Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534)
- Dose Escalation Part 1: Area Under the Serum Concentration-Time Curve From the Time of Dosing 336 Hours (AUC0-336 [hr]) of Avelumab(Pre-dose up to 336 hours post-dose, assessed up to approximately 876 days)
- Dose Escalation Part 1: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Avelumab(Pre-dose up to 30 days after last dose, assessed up to approximately 876 days)
- Dose Escalation (Part 1): Area Under the Plasma Concentration-Time Curve From the Time of Dosing to 24 Hours (AUC0-24 [hr]) of Lenvatinib:(Pre-dose up to 24 hours post-dose, assessed up to approximately 876 days)
- Dose Expansion Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs), Adverse Event of Special Interest (AESIs), AEs Leading to Deaths(up to Day 1534)
- Dose Expansion Part 2: Objective Response Rate (ORR) Rate According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators(up to Day 1534)
- Dose Expansion Part 2: Duration of Response (DOR) According to Response Assessment in Neuro-Oncology (RANO) Criteria as Assessed by Investigators(up to Day 1534)
- Dose Expansion Part 2: Overall Survival (OS)(up to Day 1534)
- Dose Expansion Part 2: Maximum Observed Plasma Concentration (Cmax) of Lenvatinib(Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534)
- Dose Expansion Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Lenvatinib(Pre-dose up to 30 days after last dose, assessed up to approximately Day 1534)
- Dose Expansion Part 2: Immunogenicity of avelumab as measured by ADA assay(up to Day 1534)
研究者
研究点 (10)
Loading locations...
相似试验
招募中
1 期
A Study of DM002 in Patients With Advanced Solid TumorsProstatic NeoplasmsColorectal NeoplasmsPancreatic CancerOvarian NeoplasmsEndometrial NeoplasmsSolid CarcinomaNCT06751329Xadcera Biopharmaceutical (Suzhou) Co., Ltd.280
招募中
1 期
A Safety And Efficacy Study Of Allogeneic CAR Gamma-Delta T Cells in Subjects With Relapsed/Refractory Solid TumorsSolid TumorNCT06150885Ever Supreme Bio Technology Co., Ltd.60
Unknown
1 期
Study of FCN-011 in Patients With Advanced Solid Tumor（Phase I）and NTRK Fusion Positive Advanced Solid Tumor （Phase II）Advanced Solid TumorNCT04687423Fochon Pharmaceuticals, Ltd.82
招募中
1 期
Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid TumorsAdvanced Solid TumorAdvanced Renal Cell CarcinomaSolid Tumor, AdultNCT05868174Telix Pharmaceuticals (Innovations) Pty Limited36
招募中
1 期
A Study of Oral 7HP349 (Alintegimod) in Combination With Ipilimumab Followed by Nivolumab MonotherapyAdvanced Solid TumorSkin CancerNSCLCRenal Cell CancerKidney CancerAnaplastic Lymphoma Kinase Genomic Tumor AberrationsALK Genomic Tumor AberrationsPleural MesotheliomaAdvanced CancerMetastasisMSI-HighMismatch Repair DeficiencyHepatocellular CancerNon Small Cell Lung CancerColorectal CancerHepatocellular CarcinomaMelanomaRenal Cell CarcinomaNCT063623697 Hills Pharma, LLC126