Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment
研究概览
简要总结
Background:
Ependymomas are rare tumors that arise from the ependyma. That is a tissue of the central nervous system. They can develop in the brain or the spine. They are usually treated with surgery, radiation, and/or chemotherapy. Researchers want to see if the new drug marizomib can help people with a certain kind of ependymoma.
Objective:
To see if marizomib stops tumor growth and prolongs the time that the tumor is controlled.
Eligibility:
Adults age 18 and older who have been diagnosed with ependymomas and have already been treated with standard therapies
Design:
Participants will be screened with the following tests or recent results from similar tests:
- Medical history
- Physical exam
- Neurological assessment
- Electrocardiogram (EKG) to evaluate the heart
- Review of symptoms and ability to perform normal activities
- Computed tomographic scan (CT) or magnetic resonance imaging (MRI) to produce an image of the brain or spine.
- Blood and urine tests
- Tests of tumor samples. Participants may have to have new tumor samples taken.
Participants will get the study drug in cycles. Each cycle is 4 weeks. Participants will have up to 24 cycles.
Participants will get the study drug through a small plastic tube in a vein on days 1, 8, and 15 of each cycle.
During each cycle, some screening tests will be repeated.
Participants will answer questions about their general well-being and functioning.
About 4 5 weeks after finishing the study drug, participants will have a follow-up visit. They will answer questions about their health, get a physical and a neurological exam, and have blood tests. They may have an MRI or CT scan.
...
详细描述
Background:
- Ependymomas are rare primary brain tumors arising from radial glial stem cells. They comprise 5.2% of all pediatric primary brain tumors and 1.9% of all adult primary brain tumors.
- The standard therapy for newly diagnosed ependymoma is gross total resection followed by radiation therapy. For anaplastic ependymoma, recurrence rate is high with a median progression free survival (PFS) of 2.3 years.
- There are limited chemotherapy options for recurrent ependymomas, which have already been irradiated. Therefore, there is an unmet need to target novel pathways for treatment of ependymomas.
- About 70% of supratentorial ependymomas have a characteristic signature C11 orf95-V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA) fusion which drives tumorigenesis in ependymomas by activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) transcription pathway.
- Marizomib is a second-generation irreversible proteasome inhibitor which penetrates across the blood-brain-barrier (BBB). It inhibits the activity of 20S proteasome in glioma cells, activates caspases, builds up reactive oxygen species and thus induces apoptosis. Marizomib blocks the NF-pathway by proteasome inhibition. Thus, it may have an additional targeted therapeutic effect in the RELA-fusion molecular subgroup of ependymomas.
Objective:
-To evaluate the efficacy of treatment with marizomib in RELA-fusion recurrent ependymoma and non RELA-fusion recurrent ependymoma as measured by progression-free survival at 6 months (PFS6).
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 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
1/Arm 1 Marizomib
Marizomib at days 1, 8, and 15 of each 28-day cycle
干预措施: Marizomib (Drug)
结局指标
主要结局
Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment
时间窗: 6 months
Progression was assessed by the Response assessment in neuro-oncology criteria (RANO) and is defined as a 25% increase in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Appearance of new lesions, or clear worsening of any evaluable disease. Failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
次要结局
- Symptom Interference Using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) Instrument(End of study)
- Number of Toxicities by Grade Using the Common CTCAE Version 5.0.(At end of study, up to 16 months)
- Number of Participants That Have Progressive Disease After 6 Months(6 months)
- Number of Participants With 12-month Progression-free Survival (PFS12)(12 months)
- Symptom Severity Using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) Instrument(End of study)
- Number of Participants Assessed Using the Response Assessment in Neuro-oncology Criteria (RANO) for Complete Response (CR) + Partial Response (PR)(Up to 16 months)
- Median Amount of Time Subject Survives 12 Months After Therapy(12 months after therapy)
- Overall Survival (OS) of RELAfusion and Non RELA-fusion Recurrent Ependymoma Patients Treated With Marizomib.(Start of treatment until end of study)
研究者
Mark Gilbert, M.D.
Principal Investigator
National Cancer Institute (NCI)