PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications

NCT06161519 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001534001534-C
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glioma; Medulloblastoma; Ependymoma; Glioblastoma

Keywords

Brain Tumors; Recurrent or progressive primary CNS tumors; Patient-Reported Outcomes; Spine Tumors; MYC or MYCN genes

Outcome Measures

Primary Outcomes (2)

• Phase I: To confirm the RP2D of PLX038 in participants with progressive or recurrent primary CNS tumors

  Number of Dose Limiting Toxicities (DLT).

  Days 1-42 (cycles 1-2)

• Phase II: To assess the efficacy of PLX038 at RP2D in primary CNS tumors containing MYC or MYCN amplifications

  Adjuvant cohort: Defined as the time from the PLX038 treatment start date to the date of confirmed progression/death or last follow-up. Kaplan-Meier method will be used to estimate the survival function. The median PFS as well as the 95% CI will be summarized.Recurrent cohorts: Defined as the percentage of participants having CR, PR, or SD \>= 6 months as determined by investigator per RANO and/or RECIST v1.1. The DCR and its 95% exact binomial CI will be summarized.

  5 years

Secondary Outcomes (4)

• Determine overall survival (OS)

  5 years

• Determine progression free survival (PFS)

  5 years

• Determine the treatment-related toxicities

  Days 1-60

• Longitudinally evaluate patient reported outcomes (PRO)

  5 years

Study Arms (2)

Phase I

EXPERIMENTAL

Escalating and de-escalating doses of PLX038

Drug: PLX038

Phase II

EXPERIMENTAL

RP2D of PLX038

Drug: PLX038

Interventions

PLX038 DRUG

PLX038 is given intravenously (IV) at the assigned dose level over about 1 hour on day 1 of each 21-day cycle

Phase I; Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 tumor with MYC or MYCN amplifications.
• Cohort Phase IID: Any recurrent glioblastoma without MYC or MYCN amplifications.
• NOTE 1: Recurrence or progression may involve CNS, extra CNS, or both.
• NOTE 2: The presence of MYCN or MYC amplification will be determined by NSR device (via next-generation sequencing panel TruSight(TM) Oncology 500) and the threshold of MYCN or MYC amplification for eligibility purposes is a fold change (FC) of \>= 2.5X (5 copies) with a minimum tumor content of 20%.
• Participants must have archival tumor tissue (either a block or 15 formalin-fixed paraffin-embedded (FFPE) unstained slides) available for NCI LP review of MYC or MYCN amplification status and for correlative studies:
• Cohorts Phase I, Phase IIB, Phase IIC, and Phase IID: tumor tissue obtained at any point before trial treatment initiation, but preferably from most recent surgical resection before study treatment initiation.
• Cohort Phase IIA: tumor tissue obtained at original diagnosis.
• Participants in Cohort Phase IIA must have completed surgery followed by radiation at least 4 weeks and no more than 10 weeks from the last dose of radiation prior to study treatment initiation.
• Participants in Cohorts Phase I, Phase IIB, Phase IIC, and Phase IID must have completed prior cytotoxic chemotherapy or radiation at least 4 weeks prior to study treatment initiation (at least 6 weeks if the last regimen included lomustine (CCNU) or carmustine (BCNU); at least 3 weeks if the last regimen included bevacizumab; at least 4 weeks if the last regimen included a checkpoint inhibitor or any other type of immunotherapy or cellular therapy; at least 5 half-lives if the last regimen included any investigational agent(s). Participants previously treated with PHOTON radiation to at least 2 segments of the spine must have completed radiation at least 12 months before study treatment initiation.

You may not qualify if:

• History of allergic reactions to compounds of similar chemical composition to PLX038.
• Major surgery within 2 weeks prior to study treatment initiation. NOTE: The surgery is considered major if a mesenchymal barrier is opened (pleural cavity, peritoneum, meninges).
• Participants who require treatment with strong inhibitors or inducers of CYP3A or with UGT1A1 inhibitors during the planned period of investigational treatment with PLX038. Lists including medications and substances known or with the potential to interact with CYP3A or UGT1A1 are provided in https://drug-interactions.medicine.iu.edu/maintable.
• History of treatment with pegylated topoisomerase inhibitors.
• Has documented \>= grade 2 PHOTON craniospinal irradiation (CSI) induced GI dysfunction.
• Participants with history of homozygous for the UGT1A1\*28 variant allele with severely reduced UGT1A1 activity.
• Participants positive for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV).
• Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of childbearing potential at screening).
• Participants unable to have MRIs.
• Prior or concurrent malignancy unless its natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen (https://deainfo.nci.nih.gov/advisory/ctac/1117/4-JournalClinicalOncology.pdf, https://ctep.cancer.gov/protocolDevelopment/docs/CTEP\_Broadened\_Eligibility\_Criteria\_Guidance.pdf)
• Uncontrolled intercurrent illness evaluated by history, weight, and physical exam that would limit compliance with study requirements.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Glioma; Medulloblastoma; Ependymoma; Glioblastoma; Brain Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jing Wu, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI NOB Referral Group

CONTACT

(866) 251-9686; ncinobreferrals@mail.nih.gov

Jing Wu, M.D.

CONTACT

(240) 760-6036; jing.wu3@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2023
• First Posted: December 8, 2023
• Study Start: January 31, 2024
• Primary Completion (Estimated): November 14, 2028
• Study Completion (Estimated): November 14, 2033
• Last Updated: March 19, 2026

Record last verified: 2026-03-13

Data Sharing

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

Locations

US (1)