A Phase 1 Dose-Escalation Study of RRx-001 in Combination With Whole Brain Radiation in Subjects With Brain Metastases (BRAINSTORM)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 5
- 主要终点
- Number, frequency and type of adverse events
研究概览
简要总结
In this dose-escalation study, the safety and tolerability of escalating dose levels of RRx-001 administered intravenously twice a week in subjects with brain metastases receiving whole brain radiation therapy (WBRT) will be assessed. Once a maximum tolerated dose is identified, further (up to approximately 30) participants will be recruited. The study will use MRI to monitor changes in tumor blood flow associated with RRx-001.
详细描述
The purpose of this research study is to test the safety and activity of whole brain radiation therapy with RRx-001, an experimental radiation sensitizer, in participants with brain metastases. As a radiation sensitizer, RRx-001 may increase the effect of whole brain radiation, the standard of care for brain metastases, on cancer cells in a specific target area while reducing damage to normal healthy cells. The ability to sensitize the cancer cells to radiation sets off a 'domino effect' of free radical damage in the tumor from a given amount or dose of radiation.
This study, which is called BRAINSTORM, since RRx-001 is associated with the development of a "free radical storm" in the brain tumors, is divided into two stages. In the first stage, approximately 3 participants at a time will be entered at a particular dose level of RRx-001 and then observed in order to see whether that dose results in side effects with radiation. If no bad side effects are observed, a second group of approximately 3 subjects will be given a slightly higher dose of RRx-001 and also monitored for side effects with radiation. This process will be repeated until a dose is reached, which has the most activity against the cancer cells without unacceptable side effects. At this point, more participants will be entered at this dose level until a maximum enrollment of approximately 30 participants has been reached.
RRx-001 releases a gas called nitric oxide, which widens the diameter of blood vessels, and allows the delivery of more oxygen to tumors. The presence of oxygen in tumors is critical for the effectiveness of radiation therapy, since cancer cells are about two to three times more vulnerable to radiation when oxygen is present. The reason that cancer cells are so much more vulnerable to the effects of radiation when oxygen is present is that radiation relies on the formation of harmful molecules known as free radicals that damage proteins and genetic material (DNA); without oxygen lower levels of free radicals are produced. Changes in the diameter go blood vessels will be studied by magnetic resonance imaging.
Unlike chemotherapies or other radiation sensitizers, RRx-001 does not have to enter the tumor to be effective because nitric oxide, as a gas, is able to spread or diffuse from the bloodstream into cancer cells.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Age ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •One or more brain metastases
- •Prior radiation therapy to the brain is allowed with the exception of whole brain irradiation
- •Subjects must be neurologically stable for at least 14 days prior to first dose of study drug;
- •Male and female subjects who are not surgically sterile or post-menopausal must agree to use reliable methods of birth control for the duration of the study and for 90 days after the last dose of study drug administration; male partners of female subjects should use condoms for the duration of the study, and for 90 days after the last dose of study drug administration
排除标准
- •Pregnant or lactating females
- •Any evidence of severe or uncontrolled diseases
- •Inadequate bone marrow reserve
- •Previous whole brain radiotherapy
- •Prior RRx-001 therapy
- •Insufficient recovery from all side effects of previous anticancer therapies
- •Evidence of blood clotting or bleeding abnormalities
研究组 & 干预措施
RRx-001 + WBRT
RRx-001 administered intravenously twice a week (10, 17, 33, 55 mg) in subjects with brain metastases receiving whole brain radiation therapy (WBRT).
干预措施: RRx-001 + WBRT (Drug)
结局指标
主要结局
Number, frequency and type of adverse events
时间窗: 42 days
To identify the maximum tolerated dose (MTD) of RRx-001 in combination with WBRT, defined as the dose of RRx-001 associated with a 20% probability of dose-limiting toxicity (DLT) in subjects with brain metastases
次要结局
- Brain Imaging Parameters(6 weeks)
- Objective Response Rate(4 months)
- Clinical Benefit Rate(4 months)
- Intracranial Progression Free Survival(4 months)
- Overall Survival(10 months)