Single-arm Dose-escalation Phase 1/2 Study of Olaptesed Pegol (NOX-A12) in Combination With Irradiation in Inoperable or Partially Resected First-line Glioblastoma Patients With Unmethylated MGMT Promoter With a 3-arm Expansion Group Including Fully Resected Patients and Combination With Bevacizumab or Pembrolizumab
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 27
- 试验地点
- 5
- 主要终点
- Safety - Number of patients with treatment-related adverse events as assessed by CTCAE
研究概览
简要总结
The purpose of this study is to obtain first, exploratory information on the safety and efficacy of (i) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete tumor resection, (ii) olaptesed pegol in combination with radiation therapy and bevacizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status either not amenable to resection (biopsy only) or after incomplete or complete tumor resection, (iii) olaptesed pegol in combination with radiation therapy in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after complete tumor resection, and (iv) olaptesed pegol in combination with radiation therapy and pembrolizumab in patients with newly diagnosed glioblastoma of unmethylated MGMT promoter status after either complete or incomplete tumor resection.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Cohort 1: 200 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Olaptesed pegol (Drug)
Cohort 1: 200 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Radiotherapy (Radiation)
Cohort 2: 400 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Olaptesed pegol (Drug)
Cohort 2: 400 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Radiotherapy (Radiation)
Cohort 3: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Olaptesed pegol (Drug)
Cohort 3: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6
干预措施: Radiotherapy (Radiation)
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm A: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, bevacizumab every two weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely or not resected patients
干预措施: Bevacizumab (Drug)
Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm B: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion plus radiotherapy during weeks 1-6, completely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm C: 600 mg Olaptesed pegol + Radiotherapy + 200 mg Pembrolizumab
olaptesed pegol weekly for 26 weeks administered i.v. by continuous infusion, pembrolizumab every three weeks for 26 weeks plus radiotherapy during weeks 1-6, incompletely resected patients
干预措施: Pembrolizumab (Drug)
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm D: 200 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Bevacizumab (Drug)
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm E: 400 mg Olaptesed pegol + Radiotherapy + 10 mg/kg Bevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Bevacizumab (Drug)
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm F: 600 mg Olaptesed pegol + Radiotherapy + 10 mg/kgBevacizumab
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Bevacizumab (Drug)
Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Olaptesed pegol (Drug)
Expansion group, Arm G: 600 mg Olaptesed pegol + Radiotherapy
olaptesed pegol i.v. by continuous infusion, bevacizumab every two weeks plus radiotherapy during weeks 1-6, until progression or intolerable toxicity (patients with disease progression may continue treatment with all assessments if deemed appropriate by the investigator), incompletely resected patients
干预措施: Radiotherapy (Radiation)
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy
oral treatment up to 35 weeks according to current SPC
干预措施: Radiotherapy (Radiation)
Expansion group, Arm H: Standard of care - Temozolomide + Radiotherapy
oral treatment up to 35 weeks according to current SPC
干预措施: Temozolomide (TMZ) (Drug)
结局指标
主要结局
Safety - Number of patients with treatment-related adverse events as assessed by CTCAE
时间窗: through study completion, an average of 3 years
Number of patients with treatment-related adverse events as assessed by CTCAE
次要结局
- Efficacy - progression free survival at 6 months (PFS-6)(6 months)
- Efficacy - Median progression-free survival (mPFS)(until end of treatment, an average 1 year)
- Efficacy - Median overall survival (mOS)(through study completion, an average of 3 years)
- Efficacy - Landmark overall survival at 18 months (OS18)(18 months)
- Overall response rate (ORR)(through study completion, an average of 3 years)
- Plasma level of olaptesed pegol(9 weeks after treatment start)
- Quality of Life (QoL) EORTC QLQ-C30 Module(through study completion, an average of 3 years)
- Quality of Life (QoL) EORTC QLQ BN-20 Module(through study completion, an average of 3 years)
- Efficacy - Tumor vascularization as per vascular MRI(through study completion, an average of 3 years)
- Neurologic functions as measured by the NANO scale(24 months)