An Open Label Phase 2 Study of Intravenously Administered Crizanlizumab Alone or in Combination With Nivolumab for Glioblastoma and Melanoma With Brain Metastases
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- The proportion of treatment discontinuation events related to the treatment combination
研究概览
简要总结
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for methylguanine-DNA methyltransferase(MGMT) methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide therapy.
详细描述
A single-center, open-label, non-randomized phase I/II study to evaluate the efficacy, safety and tolerance of crizanlizumab monotherapy and in combination with nivolumab in patients with advanced glioblastoma (GB) who exhausted standard of care (SOC) therapy, patients with metastatic brain melanoma (MBM) and patients with newly diagnosed unmethylated GB.
Subjects will be screened for up to 28 days prior to treatment initiation. Eligible subjects will be allocated to one of 3 cohorts:
Cohort 1: Patients with metastatic melanoma with primarily diagnosed or newly progressing brain metastases who failed immunotherapy.
Cohort 2: Patients with recurrent or progressing GB following primary radiation therapy and temozolomide. Patients may have failed up to 2 prior systemic treatment lines (including temozolomide as adjuvant therapy) and are candidates for further treatment.
Cohort 3: Patients with newly diagnosed GB who were evaluated for MGMT methylation status and have un-methylated MGMT promotor-therefore, they are not candidates for maintenance temozolomide 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
- 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 2 - Patients with recurrent or progressing GB following radiation and temozolamide.
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression
干预措施: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] (Drug)
Cohort 2 - Patients with recurrent or progressing GB following radiation and temozolamide.
The first 3 subjects enrolled to Cohort 1 and Cohort 2 will receive crizanlizumab 5 mg/kg at Cycle 1 Day 1 (C1D1) and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks until disease progression The subsequent 8 patients will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by 5 mg/kg every 4 weeks plus nivolumab 3mg/kg every 2 weeks until disease progression
干预措施: Nivolumab 10 MG/1 ML Intravenous Solution [OPDIVO] (Drug)
Cohort 3: Patients with newly diagnosed GB
crizanlizumab starting from 4 weeks after completing radiation therapy. The first 2 subjects will receive crizanlizumab 2.5 mg/kg at C1D1 and C1D15 followed by crizanlizumab 5 mg/kg every 4 weeks. The subsequent 6 subjects will receive crizanlizumab 5 mg/kg at C1D1 and C1D15 followed by crizanlizumab every 4 weeks. Treatment will continue for up to 12 months or until disease progression or unacceptable toxicity.
干预措施: Crizanlizumab-Tmca 10 MG/1 ML Intravenous Solution [ADAKVEO] (Drug)
结局指标
主要结局
The proportion of treatment discontinuation events related to the treatment combination
时间窗: 48 months
Safety and tolerability assessed by CTCAE v 6.0
Incidence of treatment-related adverse, serious adverse events, immune-related AEs following treatment with crizanlizumab alone or in combination with nivolumab
时间窗: 48 months
Safety and tolerability assessed by CTCAE v 6.0
次要结局
- Response Rate (RR) to crizanlizumab monotherapy and in combination with nivolumab(48 months)
- Overall survival (OS) in patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab.(48 months)
- Progression-free survival (PFS) of patients with GB or MBM following treatment crizanlizumab monotherapy and in combination with nivolumab(evaluated every 8 weeks for 48 months)
- Incidence of treatment-related adverse, serious adverse events, immune-related AEs of crizanlizumab maintenance therapy following whole-brain irradiation in patients with unmethylated GB(48 months)
- Impact of the treatment protocol on health-related quality of life(evaluated every 6 weeks for 48 months)
- Disease control rate (DCR)(48 months)
研究者
Dr. Ronnie Shapira
M.D, Head onco-gynecological service, Principal Investigator
Sheba Medical Center