Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma

NCT03727841 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 19001119-C-0011
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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. 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. ...

Conditions

Anaplastic Ependymoma; Ependymoma; Ependymomas

Keywords

Proteasome Inhibitor; Penetration Across the Blood-Brain-Barrier (BBB); Apoptosis Induction; Targeted Therapeutic Effect; Tumor Progression

Outcome Measures

Primary Outcomes (1)

• 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).

  6 months

Secondary Outcomes (8)

• 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

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 14 months and 27 days, and 7 months and 22 days for the first and second group respectively.

Study Arms (2)

1/Arm 1 Marizomib

EXPERIMENTAL

Marizomib at days 1, 8, and 15 of each 28-day cycle

Drug: Marizomib

P/Pregnancy Evaluation

NO INTERVENTION

Data collection on pregnancy, birth and Health of Child

Interventions

Marizomib DRUG

0.8mg/m(2) intravenous (IV) on days 1, 8, and 15 of each 28-day cycle, 24 cycles total.

Also known as: MRZ

1/Arm 1 Marizomib

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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,
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 27022130 BACKGROUND

• Harrison 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.

  PMID: 27117181 BACKGROUND

• Di 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.

  PMID: 26681765 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Ependymoma; Disease Progression

Interventions

marizomib

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Mark Gilbert
• Organization: National Cancer Institute

mark.gilbert@nih.gov

240-760-6023

Study Officials

• Mark R Gilbert, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 1, 2018
• Study Start: January 22, 2020
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: July 27, 2022
• Results First Posted: November 30, 2021

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: BTRIS: Clinical data available during the study and indefinitely. dbGaP: Genomic data are available once genomic data are uploaded per protocol genomic data sharing (GDS) plan for as long as database is active.
• Access Criteria: BTRIS: Clinical data will be made available via subscription to BTRIS and with the permission of the study principal investigator (PI). dbGaP: Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)