NCT06161519 PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
| NCT ID | NCT06161519 |
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Sponsor | National Cancer Institute (NCI) |
| Condition | Glioma |
| Study Type | INTERVENTIONAL |
| Enrollment | 146 participants |
| Start Date | 2024-01-31 |
| Primary Completion | 2028-11-14 |
Eligibility & Interventions
Eligibility Fast-Check
Enter your details for a quick preliminary check. This does not replace medical advice.
What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 146 participants in total. It began in 2024-01-31 with a primary completion date of 2028-11-14.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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.
Eligibility Criteria
* 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 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. * Age \>= 18 years. * Karnofsky \>= 70%. NOTE: Participants with severe paraparesis/paraplegia who need minimal assistance for self-care due to their motor deficit but are otherwise functionally independent will be eligible. * Participants must have adequate organ and marrow function as defined below: * leukocytes \>=3,000/microliter * absolute neutrophil count \>1,500/microliter * platelets \>100,000/microliter * hemoglobin \>= 9 g/ dL (may be transfused within 2 weeks prior to treatment to achieve this level) * total bilirubin within normal institutional limits * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \<2.5 X institutional upper limit of normal (ULN) * creatinine within normal institutional limits OR * estimated glomerular filtrate rate (eGFR) using chronic kidney disease epidemiology collaboration) (CKD-EPI) equation:\>= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal * Women of child-bearing potential (WOCBP) and those who can father children must agree to use effective contraception (barrier, hormonal contraception, intrauterine device (IUD), surgical sterilization, barrier at the study entry, for the duration of study treatment and up to 6 months (WOCBP) and 3 months (those who can father children) after the last dose of study treatment. * Breastfeeding participants must be willing to discontinue breastfeeding from study treatment initiation through 6 months after the last dose of the study drug. * Ability to self-report symptoms and physical function as determined by assessment of the clinical team performed at screening. * Participants must be able to understand and willing to sign a written informed consent document. EXCLUSION CRITERIA: * 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.
Contact & Investigator
Jing Wu, M.D.
PRINCIPAL INVESTIGATOR
National Cancer Institute (NCI)
Frequently Asked Questions
Who can join the NCT06161519 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, up to 120 Years, studying Glioma. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT06161519 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT06161519 currently recruiting?
Yes, NCT06161519 is actively recruiting participants. Contact the research team at ncinobreferrals@mail.nih.gov for enrollment information.
Where is the NCT06161519 trial being conducted?
This trial is being conducted at Bethesda, United States.
Who is sponsoring the NCT06161519 clinical trial?
NCT06161519 is sponsored by National Cancer Institute (NCI). The principal investigator is Jing Wu, M.D. at National Cancer Institute (NCI). The trial plans to enroll 146 participants.