Anaplastic EpendymomaPhase 2NCT03727841
Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
A Phase 2 study testing Marizomib in people with Anaplastic Ependymoma and Ependymoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Anaplastic Ependymoma, Ependymoma, Ependymomas
- What is being tested?
- Marizomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Jan 2020to 30 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Stage 1 Eligibility (Cohort 1 and 2)
- Cohort 1
- Histologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology intra-cranial or spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)- fusion ependymoma of grade I, II or III.
- Has received two or fewer prior chemotherapy regimens
- Cohort 2
- Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal RELA-fusion ependymoma of grade I, II or III.
Show all 34Show fewer
- Has received more than two prior chemotherapy regimens
- Stage 2 Eligibility (Cohorts 3 and 4)
- Cohort 3
- Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III.
- Has received two or fewer prior chemotherapy regimens
- Cohort 4
- Histologically confirmed by NCI Laboratory of Pathology intra-cranial or spinal non RELA-fusion ependymoma of grade I, II or III.
- Has received more than two prior chemotherapy regimens.
- Patients must have an evidence of tumor progression.
- Patients must have had prior radiation therapy.
- Patients must be greater than or equal to 18 years old. Currently, no dosing or adverse event data is available on the use of marizomib in patients < 18 years of age; therefore, only adults are included in this study. Patients < 18 years of age will be eligible for future pediatric trials.
- Patients must have a Karnofsky performance status of greater than or equal to 60.
- Patients must have adequate organ and marrow function as defined below:
- leukocytes: greater than or equal to 3,000/microliters
- absolute neutrophil count: greater than or equal to 1,500/microliters
- platelets: greater than or equal to 100,000/microliters
- hemoglobin: greater than or equal to 10 gm/dL (can be achieved by transfusion)
- Aspartate aminotransferase (AST) Serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) Serum glutamic pyruvic transaminase (SGPT): less than or equal to 2.5 X institutional upper limit of normal
- Bilirubin: <1.5 mg/dL
- Creatinine up to 1.5-times upper institutional limits OR estimated glomerular filtration rate (eGFR) within normal as predicted by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (greater than or equal to 60 mL/min/1.73m(2).
- Negative urine protein or urine protein concentration less than or equal to 60 mg/dL
- The effects of marizomib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and up to 30 days after the last dose of the drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Because the drug manufacturer would like to study the effect of the study therapy on pregnancy, and because the required information cannot be collected unless a subject is enrolled per ruling of the OGC, the following additional groups of subjects may be enrolled if necessary.
- -A child whose parent (male or female) is/was an active participant in the study at any time during the childs gestation. Active participant is defined as having received at least one dose of study therapy through 6 months after the last dose of study therapy.
- OR
- An expectant mother of child whose father is/was an active participant in the study at any time during the childs gestation. The father must have received at least one dose of study therapy. Active participant is defined as having received at least one dose of study therapy through 6 months after the last dose of study therapy.
- The expectant mother must be age 18 or older and must have the capacity to provide informed consent.
Who cannot join
- Anticancer treatment within designated period of time before enrollment including:
- surgery within 14 days
- needle or core biopsy within 7 days
- prior cytotoxic therapy within 28 days,
- vincristine within 14 days
- nitrosoureas within 42 days,
Show all 23Show fewer
- procarbazine administration within 21 days
- non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid (radiosensitizer does not count) within 7 days; Avastin within 21 days. Any questions related to the definition of non-cytotoxic agents should be directed to the NCI Principal Investigator.
- Treatment with any investigational agent within 28 days before enrollment.
- History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless patient is in complete remission and off all therapy for that disease for a minimum of 3 years.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to marizomib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Inadequately controlled hypertension (defined as systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg).
- Current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
- New York Heart Association (NYHA) Grade II heart failure or greater or history of hospitalization for congestive heart failure diagnosis within 12 months prior to enrollment.
- History of myocardial infarction or unstable angina within 3 months prior to enrollment.
- A marked baseline prolongation of QT interval (QT)/corrected QT interval (QTc) (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using Frederica's QT correction
- formula.
- A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- Current use of concomitant medications that prolong the QT/QTc interval
- History of stroke or transient ischemic attack within 3 months prior to enrollment.
- Pregnant women are excluded from this study because marizomibs potential for teratogenic or abortifacient effects is unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with marizomib, breastfeeding should be discontinued if the mother is treated with marizomib.
- Patients receiving combination antiretroviral therapy for treatment of Human Immunodeficiency Virus (HIV) or active anti-viral treatment for Hepatitis A, B or C infection. Anti-viral therapy, when combined with marizomib, poses a potential for pharmacokinetic interactions. Marizomib also increases immunosuppression, placing patients at an increased risk of acquiring lethal infections. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
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.
Read more
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.
...
Read the detailed description
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:
- 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.
Design:
- 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.
- Conditions
- Anaplastic Ependymoma, Ependymoma, Ependymomas
- Being tested
- Marizomib
- Keywords
- Proteasome Inhibitor, Penetration Across the Blood-Brain-Barrier (BBB), Apoptosis Induction, Targeted Therapeutic Effect, Tumor Progression
- Medical subject headings
- Ependymoma, Disease Progression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MarizomibDrug
Also called MRZ
0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total.
| Study group | Role | What they receive |
|---|---|---|
| 1/Arm 1 Marizomib | Experimental | Marizomib at days 1, 8, and 15 of each 28-day cycle Receives: Drug: Marizomib |
| P/Pregnancy Evaluation | No intervention | Data collection on pregnancy, birth and Health of Child |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment
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).
Measured: 6 months
Secondary outcomes (8)
Number of Toxicities by Grade Using the Common CTCAE Version 5.0.
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).
Measured: At end of study, up to 16 months
Number of Participants That Have Progressive Disease After 6 Months
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 progression free disease after 6 months. Progression was assessed by the Response Assessment in Neuro-oncology (RANO) criteria 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).
Measured: 6 months
Number of Participants With 12-month Progression-free Survival (PFS12)
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).
Measured: 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
Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom severity.To longitudinally evaluate participant reported outcome measures using self-reported symptom severity with daily activities using the MDASI-BT and/or MDASI-SP instrument.
Measured: End of study
Number of Participants Assessed Using the Response Assessment in Neuro-oncology Criteria (RANO) for Complete Response (CR) + Partial Response (PR)
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. Complete Response is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Partial Response is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions.
Measured: Up to 16 months
Median Amount of Time Subject Survives 12 Months After Therapy
Median amount of time subject survives 12 months after therapy
Measured: 12 months after therapy
Overall Survival (OS) of RELAfusion and Non RELA-fusion Recurrent Ependymoma Patients Treated With Marizomib.
OS is defined as the time from treatment start date until date of death or date last known alive.
Measured: Start of treatment until end of study
Symptom Interference Using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) Instrument
Changes in quality of life using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) instrument was used to determine symptom interference.To longitudinally evaluate participant reported outcome measures using self-reported symptom interference with daily activities using the MDASI-BT and/or MDASI-SP instrument.
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2018
- Study start22 Jan 2020
- Primary completion30 Apr 2021
- Study completion30 Apr 2021
Why it stopped: The pharmaceutical company decided to close their program evaluating the study agent, Marizomib.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Anaplastic EpendymomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Mark Gilbert, M.D., National Cancer Institute (NCI)
- Investigators
- Mark R Gilbert, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03727841
- Sponsor's protocol ID
- 190011
- Other IDs
- 19-C-0011
- Status last verified
- Jul 2022
- First submitted
- 31 Oct 2018
- Last updated
- 27 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 1. Biomedical Translational Research Information System (BTRIS): All IPD recorded in the medical record will be shared with intramural investigators upon request. 2. Database of Genotypes and Phenotypes (dbGaP): All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Publications
Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro Oncol. 2016 Jul;18(7):902-13. doi: 10.1093/neuonc/now016. Epub 2016 Mar 28.
PubMed 27022130Harrison SJ, Mainwaring P, Price T, Millward MJ, Padrik P, Underhill CR, Cannell PK, Reich SD, Trikha M, Spencer A. Phase I Clinical Trial of Marizomib (NPI-0052) in Patients with Advanced Malignancies Including Multiple Myeloma: Study NPI-0052-102 Final Results. Clin Cancer Res. 2016 Sep 15;22(18):4559-66. doi: 10.1158/1078-0432.CCR-15-2616. Epub 2016 Apr 26.
PubMed 27117181Di K, Lloyd GK, Abraham V, MacLaren A, Burrows FJ, Desjardins A, Trikha M, Bota DA. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Neuro Oncol. 2016 Jun;18(6):840-8. doi: 10.1093/neuonc/nov299. Epub 2015 Dec 17.
PubMed 26681765
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Trial of Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma
- ClinicalTrials.gov ID
- NCT03727841
- Acronym / sponsor ID
- 190011
- Conditions
- Anaplastic Ependymoma, Ependymoma, Ependymomas
- Keywords
- Proteasome Inhibitor, Penetration Across the Blood-Brain-Barrier (BBB), Apoptosis Induction, Targeted Therapeutic Effect, Tumor Progression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The pharmaceutical company decided to close their program evaluating the study agent, Marizomib.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 22 Jan 2020 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 30 Apr 2021 (actual)
- First posted
- 1 Nov 2018 (actual)
- Results
- Posted 30 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
Detailed description
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:
- 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.
Design:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/Arm 1 Marizomib | Experimental | Drug: MarizomibMarizomib at days 1, 8, and 15 of each 28-day cycle |
| P/Pregnancy Evaluation | No intervention | –Data collection on pregnancy, birth and Health of Child |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (34 listed)
- Stage 1 Eligibility (Cohort 1 and 2)
- Cohort 1
- Histologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology intra-cranial or spinal V-Rel Avian Reticuloendotheliosis Viral Oncogene Homolog A (RELA)- fusion ependymoma of grade I, II or III.
- Has received two or fewer prior chemotherapy regimens
- Cohort 2
Key exclusion criteria (23 listed)
- Anticancer treatment within designated period of time before enrollment including:
- Treatment with any investigational agent within 28 days before enrollment.
- History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless patient is in complete remission and off all therapy for that disease for a minimum of 3 years.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to marizomib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MarizomibAlso: MRZ0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total. | Drug | 1/Arm 1 Marizomib |
Primary outcome
Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment
Time frame: 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).
8 secondary outcomes
Number of Toxicities by Grade Using the Common CTCAE Version 5.0.
Time frame: At end of study, up to 16 months
Number of Participants That Have Progressive Disease After 6 Months
Time frame: 6 months
Number of Participants With 12-month Progression-free Survival (PFS12)
Time frame: 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
Time frame: End of study
Number of Participants Assessed Using the Response Assessment in Neuro-oncology Criteria (RANO) for Complete Response (CR) + Partial Response (PR)
Time frame: Up to 16 months
Median Amount of Time Subject Survives 12 Months After Therapy
Time frame: 12 months after therapy
Overall Survival (OS) of RELAfusion and Non RELA-fusion Recurrent Ependymoma Patients Treated With Marizomib.
Time frame: Start of treatment until end of study
Symptom Interference Using the MD Anderson Symptom Inventory- Brain Tumor (MDASI-BT) and/or MD Anderson Symptom Inventory - Spine Tumor Module (MDASI-SP) Instrument
Time frame: End of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27022130Wu J, Armstrong TS, Gilbert MR. Biology and management of ependymomas. Neuro Oncol. 2016 Jul;18(7):902-13. doi: 10.1093/neuonc/now016. Epub 2016 Mar 28.
- Background: PubMed 27117181Harrison SJ, Mainwaring P, Price T, Millward MJ, Padrik P, Underhill CR, Cannell PK, Reich SD, Trikha M, Spencer A. Phase I Clinical Trial of Marizomib (NPI-0052) in Patients with Advanced Malignancies Including Multiple Myeloma: Study NPI-0052-102 Final Results. Clin Cancer Res. 2016 Sep 15;22(18):4559-66. doi: 10.1158/1078-0432.CCR-15-2616. Epub 2016 Apr 26.
- Background: PubMed 26681765Di K, Lloyd GK, Abraham V, MacLaren A, Burrows FJ, Desjardins A, Trikha M, Bota DA. Marizomib activity as a single agent in malignant gliomas: ability to cross the blood-brain barrier. Neuro Oncol. 2016 Jun;18(6):840-8. doi: 10.1093/neuonc/nov299. Epub 2015 Dec 17.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 1. Biomedical Translational Research Information System (BTRIS): All IPD recorded in the medical record will be shared with intramural investigators upon request. 2. Database of Genotypes and Phenotypes (dbGaP): All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Related trials for Anaplastic Ependymoma
RecruitingPhase 1
Phase I Study of Oral ONC206 in Recurrent and Rare Primary Central Nervous System Neoplasms
Central Nervous System Neoplasms, Glioblastoma
RecruitingPhase 1
HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
Neoplasms, Brain, Glioblastoma Multiforme
Recruiting
Individualized Treatment Plan in Children and Young Adults With Relapsed Medulloblastoma and Ependymoma
Medulloblastoma, Medulloblastoma, Childhood
RecruitingPhase 1/2
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
High Grade Glioma, Meningioma
Active, not recruitingPhase 1
A Pilot Study of SurVaxM in Children Progressive or Relapsed Medulloblastoma, High Grade Glioma, Ependymoma and Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Medulloblastoma, Glioblastoma Multiforme
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark R Gilbert, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Marizomib in people with Anaplastic Ependymoma and Ependymoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Are Progression-free at 6 Months Time Point After Initiation of Treatment (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03727841, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2022.