Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
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|ClinicalTrials.gov Identifier: NCT03727841|
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : October 8, 2020
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.
To see if marizomib stops tumor growth and prlongs the time that the tumor is controlled.
Adults age 18 and older who have been diagnosed with ependymomas and have already been treated with standard therapies
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.
|Condition or disease||Intervention/treatment||Phase|
|Anaplastic Ependymoma Ependymoma Ependymomas||Drug: Marizomib||Phase 2|
- 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 C11orf95-RELA fusion which drives tumorigenesis in ependymomas by activating the 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.
-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).
- Histologically proven intra-cranial or spinal ependymoma.
- Radiographic evidence of tumor progression
- Patients must be greater than or equal to 18 years old.
Patients must have had prior radiotherapy.
- This is a phase II study to determine the efficacy of marizomib in recurrent ependymoma.
- A novel 2-stage sequential design will be employed to conduct the trial for recurrent ependymoma.
- In the first stage, we will enroll 18 patients with RELA-fusion ependymoma and if 4 or more patients in Cohort 1 are progression free at 6 months, we will proceed to stage 2; otherwise we will terminate the trial and conclude that marizomib is not effective.
- In the second stage, we will enroll 32 patients with non RELA-fusion ependymoma.
- Patients will be treated with marizomib in cycles consistent of 28 days until disease progression or a maximum of 24 cycles.
|Study Type :||Interventional|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma|
|Actual Study Start Date :||January 22, 2020|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2026|
Experimental: 1/Arm 1
Marizomib at days 1, 8, and 15 of each 28-day cycle
0.8mg/m2 IV on days 1, 8, and 15 of each 28-day cycle, 24 cycles total.
- Progression-free survival (PFS) [ Time Frame: 6 months ]Proportion of patients that are progression-free at 6 months time point after initiation of treatment
- Number of toxicities by grade and type scored using CTCAE version 5.0. [ Time Frame: end of study ]To determine the safety of marizomib in recurrent ependymoma patients and in a subset of patients with more than 2 prior chemotherapies (RELA-fusion Cohort 2 and non-RELA-fusion Cohort 4).
- Proportion of patients that have progressive disease after 6, 12 months. Median amount of time subject survives after therapy [ Time Frame: 6 month, 12 month and end of study ]To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by PFS6, PFS12, median PFS and OS.
- Median amount of time subject survives without disease progression after treatment and Median amount of time subject survives 12 months after therapy [ Time Frame: 12 month and end of study ]To estimate the 12-month progression-free survival (PFS12), median progressionfree survival (PFS) and overall survival (OS) of RELAfusion and non RELA-fusion recurrent ependymoma patients treated with marizomib.
- Proportion of patients that have changes in quality of life [ Time Frame: end of study ]To longitudinally evaluate patient reported outcome measures using self-reported symptom severity and interference with daily activities using the MDASI-BT and/or MDASI-SP instrument.
- Proportion of patients assessed using the RANO Criteria for Response [ Time Frame: end of study ]To estimate the efficacy of marizomib in recurrent ependymoma patients (RELA- fusion Cohort 2 and non RELA-fusion Cohort 4) with more than 2 prior chemotherapies as measured by objective response.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727841
|Contact: Kathleen Wall (Mendoza)||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Mark R Gilbert, M.D.||National Cancer Institute (NCI)|