Phase I Study of Ruxolitinib With Radiation and Temozolomide in Patients With Newly Diagnosed Grade III Gliomas and Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients
研究概览
简要总结
The purpose of this study is to test how well the drug works, safety and tolerability of an investigational drug called Ruxolitinib in gliomas and glioblastomas, when combined with standard treatment for brain cancer, temozolomide and radiation.
Ruxolitinib is an experimental drug that works by targeting proteins in cells and stops them from growing. Ruxolitinib is experimental because it is not approved by the Food and Drug Administration (FDA) for the treatment of gliomas or glioblastomas
Temozolomide works by damaging the DNA of tumor cells so that they cannot divide properly. Some tumor cells can repair that damage and therefore be resistant to temozolomide.
详细描述
Primary Objective
Arm 1:
To determine Maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) in patients with unmethylated MGMT high-grade glioma (HGG)
Arm 2:
To determine Maximum tolerated dose (MTD) of ruxolitinib with radiation (2 Gy x 30) and daily temozolomide at 75 mg/m2 in patients with methylated MGMT high-grade glioma (HGG)
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
- •Patients must have unmethylated MGMT supratentorial high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma).
- •Patients must have supratentorial methylated MGMT high-grade glioma (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed astro oligodendroglioma or glioblastoma).
- •Patients must have MRI or CT with contrast within 28 days prior to starting treatment.
- •Patients must have a Karnofsky performance status ≥ 70% (i.e. the patient must be able to care for himself/herself with occasional help from others).
- •Patients must have adequate blood, kidney and liver function
- •Patients must be able to provide written informed consent.
- •Patients and their sexual partners must agree to avoid conception while on the study due to possible risks from experimental drugs. Women will need a negative pregnancy test to be on the study
- •Patients may not have any other cancers except skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago
排除标准
- •Patients with other serious diseases
- •Pregnant women
- •Patients getting other cancer treatments
- •Patients with other cancers except for localized skin cancer and localized bladder, prostate, cervical, or breast cancer which were cured more than 3 years ago
- •Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.
- •Patients who have previously received other treatments for their cancers
- •Patient has previously taken ruxolitinib or is allergic to components of the study drug
- •Use of blood thinners
- •Human immunodeficiency virus (HIV) infection
- •Active hepatitis B or C infection
- •Heart diseases including abnormal electrocardiogram (EKG)
- •Patients unwilling or unable to follow this protocol
研究组 & 干预措施
ruxolitinib + radiation x 60 Gy for 6 weeks
Unmethylated O6-methylguanine DNA methyltransferase (MGMT) Glioblastoma and grade III glioma Every patient gets ruxolitinib + radiation x 60 Gy for 6 weeks over 6 weeks. The dose of radiation therapy is fixed at 60 Gy over 6 weeks
干预措施: radiation (Radiation)
ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m
Methylated MGMT Glioblastoma and grade III glioma. Arm 2 will start once the safe dose has been established for Arm 1 for every dose level.
Every patient gets ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks.
The dose of radiation therapy is fixed at 60 Gy over 6 weeks (2 Gy x 30). The dose of temozolomide is 75 mg/m2 daily for 6 weeks
干预措施: ruxolitinib (Drug)
ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m
Methylated MGMT Glioblastoma and grade III glioma. Arm 2 will start once the safe dose has been established for Arm 1 for every dose level.
Every patient gets ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks.
The dose of radiation therapy is fixed at 60 Gy over 6 weeks (2 Gy x 30). The dose of temozolomide is 75 mg/m2 daily for 6 weeks
干预措施: radiation (Radiation)
ruxolitinib + radiation x 60 Gy for 6 weeks
Unmethylated O6-methylguanine DNA methyltransferase (MGMT) Glioblastoma and grade III glioma Every patient gets ruxolitinib + radiation x 60 Gy for 6 weeks over 6 weeks. The dose of radiation therapy is fixed at 60 Gy over 6 weeks
干预措施: ruxolitinib (Drug)
ruxolitinib + radiation x 60 Gy + temozolomide 75 mg/m
Methylated MGMT Glioblastoma and grade III glioma. Arm 2 will start once the safe dose has been established for Arm 1 for every dose level.
Every patient gets ruxolitinib + radiation x 60 Gy + daily temozolomide at 75 mg/m2 for 6 weeks over 6 weeks.
The dose of radiation therapy is fixed at 60 Gy over 6 weeks (2 Gy x 30). The dose of temozolomide is 75 mg/m2 daily for 6 weeks
干预措施: temozolomide (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of ruxolitinib with radiation and daily Temozolomide in study patients
时间窗: Up to 6 weeks
Maximum tolerated dose (MTD) of ruxolitinib with radiation in study patients
时间窗: Up to 6 weeks
次要结局
- Number of patient study specific adverse events as a measure of safety(Up to 8 weeks after beginning treatment)
- Number of patients who have experienced progression free survival as defined by the response assessment in neuro-oncology (RANO) criteria(Up to 6 weeks)
- Average time patients stayed alive on study(Up to 6 weeks)