ClinicalTrials.gg
RecruitingNCT06161519Updated Nov 6, 2026

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

A Phase 1/2 interventional study of PLX038 in Glioma, Medulloblastoma and Ependymoma, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2026-11-06.

Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Jan 2024; still recruiting 2 years 9 months later.
Updated Nov 4, 2026Study contact changedGo to Updates ↓
Phase
Phase 1/2
Study type
Interventional
Enrollment
146
Allocation
Non-randomized
Ages
18 Years to 120 Years
Sex
All
01

Study 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.

Read the detailed 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 efficacious options. At present, they are typically treated with maximal safe surgical resection followed by external beam radiation therapy, with the variable inclusion of cytotoxic chemotherapy regimens as first-line treatment and/or at recurrence. These "standard" options have shown limited to no antitumor activity, leading to an extremely poor prognosis.
  • MYC-driven increase in transcription induces the formation of topoisome complexes (MYC-C/N, Topoisomerase 1 (TOP1), Topoisomerase 2 (TOP2), DNA) that are essential to managing the torsional strain that would otherwise oppose transcription and replication.
  • PLX038 is a PEGylated macromolecule that contains 4 molecules of SN-38, the active metabolite of irinotecan, that is currently being investigated in non-CNS solid tumor trials. SN38 binds to and inhibits topoisomerase 1 and the unique formulation of PLX038 lead to a longer half-life, which is thought to increase tumor accumulation and potentially decrease toxicity.

Objectives:

  • Phase I: To confirm the recommended Phase II dose (RP2D) of PLX038 in participants with progressive or recurrent primary CNS tumors.
  • Phase II: To assess the efficacy of PLX038 at RP2D in primary CNS tumors based on MYC or MYCN amplifications as measured by:

    • Progression-free survival (PFS) for Cohort Phase IIA (adjuvant treatment), and
    • Disease control rate (DCR), defined as confirmed complete response (CR) / partial response (PR) or durable stable disease (SD) (NOTE: Durable SD is SD lasting for at least 6 months) for Cohorts Phase IIB and Phase IIC (treatment for recurrence with a MYC or MYCN amplification).
    • Progression free Survival at 6 months (PFS6) for Cohort phase IID (recurrent glioblastoma without a MYC or MYCN amplification)

Eligibility:

  • Subjects with histologically confirmed primary CNS tumors corresponding to any progressive or recurrent tumor type (Phase I) or one of the following tumor types (Phase II):

    • Cohort Phase IIA: Newly diagnosed MYCN amplified ependymoma post resection and radiotherapy.
    • Cohort Phase IIB: Recurrent or progressive MYCN amplified ependymoma or medulloblastoma with MYC or MYCN amplifications.
    • Cohort Phase IIC: All other recurrent or progressive primary CNS tumors containing MYC or MYCN amplifications.
    • Cohort Phase IID: Recurrent glioblastoma that does not contain MYC or MYCN amplifications.
  • Age >= 18 years.
  • Karnofsky Performance Status >= 70%.
  • Ability to self-report symptoms and physical function as determined by assessment of the clinical team.
  • Tumor tissue availability for central review and correlative studies.

Design:

This is an open-label phase I/II clinical trial.

  • During Phase I RP2D and maximum tolerated dose (MTD) of PLX038 will be estimated.
  • In the Phase II component, participants will be treated with the TOP1 inhibitor PLX038 at the RP2D intravenously every 3 weeks (+/- 3 days, = 1 cycle). The Phase II study will be comprised of 4 independent disease cohorts that can enroll simultaneously and will be evaluated independently for efficacy.
  • Treatment will continue until progression or unacceptable toxicity, or a maximum of 10 cycles, whichever occurs first.
  • Safety and toxicity assessments will occur prior to each treatment cycle (every 3 weeks).
  • Efficacy (by magnetic resonance (MR) imaging and/or other imaging techniques if extra CNS tumor is present) and patient-reported outcomes measures (PROs): participant reported toxicity using predetermined patient-reported outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) symptoms, Patient Global Impression of Severity (PGI-S), Patient Global Impression-Change (PGI-C), Overall Side Effect Bother, self-reported symptom severity and interference with daily activities using MD Anderson Symptom Inventory for brain tumor (MDASI-BT), and/or MD Anderson Symptom Inventory for spine tumors (MDASI-SP) questionnaires; self-reported physical functioning using Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Functioning form 10b. PRO-CTCAE, PGI-S, PGI-C, Overall Side Effect Bother, and PROMIS Physical Function 10b will be obtained at baseline and weekly for the first two cycles of treatment then these and all other PRO assessments will be obtained at the time of disease imaging evaluation every 2 cycles (6 weeks). The only exceptions are the PGI-C and Overall Side Effect Bother which will not be obtained at baseline and Day 1 of Cycle 1. PRO measures will be completed prior to participants being informed of imaging results.
  • PLX038 drug distribution will be investigated in peripheral blood and tumor tissue post-treatment administration. Molecular biomarkers of treatment response or resistance will be investigated in an exploratory manner pre and post-treatment (after cycle 2 and after tumor progression) in tumor tissue, hair follicles, and peripheral blood.
02

Conditions studied

  • Glioma
  • Medulloblastoma
  • Ependymoma
  • Glioblastoma

Keywords

  • Brain Tumors
  • Recurrent or progressive primary CNS tumors
  • Patient-Reported Outcomes
  • Spine Tumors
  • MYC or MYCN genes
03

In context

Glioma

1,452 studies on the registry are indexed under Glioma; 349 are open to participants now.

This study's planned enrollment of 146 is above the median of 32 across 1,075 interventional studies indexed under Glioma.

Browse Glioma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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 must be confirmed by documented history. Participants who do not have documented history will be tested 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 (either a block or 15 formalin-fixed paraffin-embedded (FFPE) unstained slides) available for NCI LP review of MYC or MYCN amplification status (if necessary) 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 or any other type of immunotherapy or cellular therapy; at least 5 half-lives if the last regimen included any agent(s).
  • Age >= 18 years.
  • >= 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
    • >1,500/microliter
    • >100,000/microliter
    • >= 9 g/ dL (may be transfused within 2 weeks prior to treatment to achieve this level)
    • total within normal institutional limits
    • (AST) / alanine aminotransferase (ALT) \<2.5 X institutional (ULN)
    • creatinine within normal institutional limits OR
    • estimated glomerular filtrate rate () 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 (WOCBP) and those who can father children must agree to use effective (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 document.

Exclusion criteria

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 or with UGT1A1 inhibitors during the planned period of 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 unresolved or persistent grade 2 or higher GI toxicity from any type of RT at screening
  • Participants with history of homozygous for the UGT1A1*28 variant allele with severely reduced UGT1A1 activity.
  • Participants positive for (HIV), virus (HCV), and virus (HBV).
  • Pregnancy (confirmed with beta human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test performed in females of at screening).
  • Participants unable to have MRIs.
  • Prior or concurrent 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.
Terms in these criteria, in plain language(19)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
146 participants (estimated)

Study arms

  • Experimental
    Phase I

    Escalating and de-escalating doses of PLX038

    Drug: PLX038

  • Experimental
    Phase II

    RP2D of PLX038

    Drug: PLX038

Interventions

06

What researchers measure

Primary outcomes

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

    Number of Dose Limiting Toxicities (DLT).

    Time frame: Days 1-42 (cycles 1-2)

  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.

    Time frame: 5 years

Secondary outcomes

  1. Determine overall survival (OS)

    Measured the time from the start of PLX038 treatment to the date of death or last follow-up. OS will be estimated using the methods of Kaplan and Meier. The median OS and its 95%CI will be summarized. (All cohorts)

    Time frame: 5 years

  2. Determine progression free survival (PFS)

    Defined as the time from the PLX038 treatment start date to the date of conformed 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)

    Time frame: 5 years

  3. Determine the treatment-related toxicities

    Clinical safety data (i.e., vital signs, ECGs, routine laboratory tests, physical examinations, and AEs) will be summarized using descriptive statistics (e.g., mean, frequency) using the safety analysis set (SAS). All the toxicity data will be summarized by dose level and by cohort.

    Time frame: Days 1-60

  4. Longitudinally evaluate patient reported outcomes (PRO)

    Feasibility of PRO data collection for each questionnaire will be evaluated by calculating the compliance rates which is the number of received valid forms over the number of expected forms. Analysis of results will be based upon each separate questionnaire type to determine meaningful change.

    Time frame: 5 years

07

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
08

References and documents

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report

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.

09

Updates

3 registry updates since Sep 25, 2026
Contact
Study contact changed: j•••@nih.gov · •••6036→c•••@mail.nih.gov · •••6205. See the current contact
Nov 4, 2026
Show all 3 updates
  1. Nov 6, 2026
    Minor edits only
    + 1 other change: verification date
  2. Nov 4, 2026
    Contact Study contact changed: j•••@nih.gov · •••6036→c•••@mail.nih.gov · •••6205. See the current contact
  3. Oct 16, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT06161519
Responsible party
Sponsor
First posted
Dec 8, 2023
Start date
Jan 31, 2024
Primary completion
Nov 14, 2028 (estimated)
Completion
Nov 14, 2033 (estimated)
Last update
Nov 6, 2026

Study contacts

NCI NOB Referral Group
Contact
ncinobreferrals@mail.nih.gov
(866) 251-9686
Kevin A Camphausen, M.D.
Contact
camphauk@mail.nih.gov
(240) 760-6205
Kevin A Camphausen, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: DFP-13318 · Pegylated SN-38 Conjugate PLX038

Start the discussion