Phase I/II Trial of PLX038 in Primary Central Nervous System Tumors With and Without MYC or MYCN Amplifications
National Cancer Institute (NCI)
Summary
Background: About 90,000 new cases of brain and spinal cord tumors are diagnosed annually in the United States. Most of these tumors are benign; however, about 30% are malignant, and 35% of people with malignant tumors in the brain and spinal cord will die within 5 years. Many of these people have changes in certain genes (MYC or MYCN) that drive the development of their cancers. Objective: To test a study drug (PLX038) in people with tumors of the brain or spinal cord. Eligibility: People aged 18 years or older with a tumor of the brain or spinal cord. Some participants must also have tumors with changes in the MYC or MYCN genes. Design: Participants will be screened. They will have a physical exam and blood tests. They will have imaging scans and a test of their heart function. They may need to have a biopsy: A sample of tissue will be removed from their tumor. PLX038 is given through a tube attached to a needle inserted into a vein in the arm. All participants will receive PLX038 on the first day of each 21-day treatment cycle. They will take a second drug 3 days later to help reduce the risk of infection; for this drug, participants will be shown how to inject themselves under the skin at home. Blood tests, imaging scans, and other tests will be repeated during study visits. Hair samples will also be collected during these visits. Some participants may have an additional biopsy. Study treatment will continue up to 7 months. Follow-up visits will continue every few months for up to 5 years.
Description
Background: * The MYC genes encode a family of transcription factors (MYC-C, MYC-N, and MYC-L) that regulate the expression of a wide range of genes involved in cell division in development and adulthood. * Supraphysiologic levels of MYC are oncogenic and drive aggressive behavior across a range of human malignancies. Amplifications of MYC and MYCN are seen in multiple types of primary central nervous system (CNS) tumors, including high-grade gliomas, medulloblastomas, and ependymomas. * These CNS tumors are rare and there are limited prospective data to inform treatment choices and few effic…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Participants must have documented pathologic diagnosis of confirmed primary central nervous system (CNS) tumor with one of the below diagnoses: * Cohort Phase I: Any recurrent or progressive primary CNS tumor, regardless of molecular features. * Cohort Phase IIA: Newly diagnosed MYCN amplified ependymoma after surgery and radiation. * Cohort Phase IIB: * Recurrent or progressive MYCN amplified ependymoma, OR * Recurrent or progressive medulloblastoma with MYC or MYCN amplifications * Cohort Phase IIC: Any other recurrent or progressive primary CNS tumo…
Interventions
- DrugPLX038
PLX038 is given intravenously (IV) at the assigned dose level over about 1 hour on day 1 of each 21-day cycle
Location
- National Institutes of Health Clinical CenterBethesda, Maryland