A Phase I Study of CAN008 Plus Concomitant Temozolomide During and After Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
研究概览
简要总结
To evaluate CAN008 safety, tolerability, and pharmacokinetics (PK) of CAN008 when administered concurrent Plus Concomitant Temozolomide During and After Radiation Therapy in Patients with Newly Diagnosed Glioblastoma Multiforme.
详细描述
CAN008 is a glycosylated fusion protein consisting of the extracellular domain of human CD95 (APO-1/Fas) and the Fc domain of human IgG1. CAN008 blocks the interaction between CD95 and its cognate ligand CD95L. The target of CAN008 is the inhibition of CD95L. CD95L is expressed in glioblastoma whose cells are resistant to CD95-mediated apoptosis. CD95L was shown to be a crucial trigger in invasion and migration of tumor cells and neutralizing CD95L abolishes the invasive capacity of glioblastoma cells.
The purpose of the study is:
- To describe the toxicity associated with this regimen in adult patients with newly diagnosed glioblastoma multiforme.
- To determine the duration of disease free survival and overall survival associated with this therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed and histologically confirmed glioblastoma multiforme
- •Tumor must be surgically accessible and tissue must be available
- •Age ≥ 20 years and < 75 years
- •Life expectancy ≥ 6 months
- •Baseline MRI images must be done within 2 days after surgery
- •Patients must have a Karnofsky performances score ≥ 60 prior to treatment.
- •Patients must not have received prior cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy for brain tumors.
- •Adequate hematologic (absolute neutrophil count (ANC) ≥ 1.5x109/L, platelet count ≥ 100x109/L, hemoglobin ≥ 10 g/dL ), renal (creatinine ≤ 1.25xULN ), and hepatic function (total bilirubin ≤ 1.5xULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5xULN)
- •Women with childbearing potential must have a negative serum pregnancy test less than 7 days prior to the first dose of study drug.
- •Both men and women of reproductive potential agree to use approved contraception, such as condom and placement of an intrauterine device (IUD), during the study and until 3 months after the discontinuation of study treatment.
- •Willing and able to comply with the protocol as judged by the investigator
- •Patients must provide written consent
排除标准
- •Any prior chemotherapy (including carmustine-containing wafers) or immunotherapy (including vaccine therapy )
- •Any prior radiotherapy to the brain
- •Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. Patients with a previous malignancy but without evidence of disease for ≥ 5 years will be allowed to enter the trial
- •Any contraindication to TMZ listed in the local label
- •Low-grade astrocytoma
- •Unable to undergo MRI
- •Past medical history of disease with poor prognosis according to the judgment of the Investigator
- •HIV infection
- •Patients with positive anti-HCV
- •Patients with positive HbsAG who received any related treatment within the past 6 months
- •Patients suffering from hereditary fructose intolerance (HFI).
- •Patients receive any investigational agent(s) or device(s) within 30 days prior to entering the study
- •Known coronary artery disease, significant arrhythmias or severe congestive heart failure
研究组 & 干预措施
CAN008
CAN008 administered as a 30 min intravenous infusion once a week until disease progression or unacceptable toxicity.
干预措施: CAN008 (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
时间窗: up to 2 years
The safety assessment will include safety laboratory (clinical chemistry, hematology, urinalysis), physical exam, vital signs and 12-lead ECG (QT prolongation). An AE can be any unfavourable and unintended sign, symptom, or disease temporarily associated with the use of a medicinal product, whether or not is considered to be related to the medicinal product. Pre-existing conditions worsen during a study are also to be reported as AEs. Furthermore, any side effects potentially related to the CAN008 treatment will be evaluated.
次要结局
- PK profile measured by Area Under the Curve [AUC](up to 2 years)
- Preliminary efficacy (Progression Free Survival after 6 months [PFS6])(up to 2 years)
- Preliminary efficacy (Overall Survival [OS])(up to 2 years)
- Recommended Dose for Phase II [RP2D] measured by the Maximum Tolerated Dose [MTD] or the Maximum Administered Dose [MAD](up to 2 years)
- PK profile measured by CAN008 serum concentrations(up to 2 years)
- PK profile measured by Maximum Plasma Concentration [Cmax](up to 2 years)