Embryonal Tumor With Multilayered Rosettes (PNOC031)

April 20, 2026 updated by: University of California, San Francisco

PNOC031: Protocol for Embryonal Tumor With Multilayered Rosettes (ETMR)

This is an open-label, comprehensive, iterative investigation of evaluating the use of induction chemotherapy, high-dose chemotherapy, and focal radiation therapy in children with newly diagnosed Embryonal Tumor With Multilayered Rosettes (ETMR).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES I. To determine the six-month progression-free survival (PFS6) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR, treated using a regimen of induction chemotherapy and early focal radiotherapy (Cohort 1)

SECONDARY OBJECTIVES I. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 1).

II. To determine the two-year progression-free survival (PFS) and overall survival (OS) of participants with newly diagnosed, gross-totally resected, non-metastatic ETMR (Cohort 2).

III. To determine the two-year progression-free survival (PFS), overall survival (OS) and objective response rate of participants with newly diagnosed, incompletely resected and/or metastatic ETMR (Cohort 3A and 3B)

EXPLORATORY OBJECTIVES:

I. To validate the utility of a liquid miRNA biomarker in blood and Cerebral spinal fluid (CSF) as a correlative marker of a participant's disease status.

II. To better define the genomic landscape of ETMR.

OUTLINE:

Participants with newly diagnosed ETMR will obtain either gross total, or sub-total resection surgery prior to enrollment. After surgery, participants will be assigned to 1 of 4 possible cohorts:

Cohorts 1 and 2: Participants with newly diagnosed, gross-totally resected, non-metastatic ETMR.

Cohorts 3A and 3B: Participants with newly diagnosed, incompletely resected and/or metastatic ETMR.

Participants will be assessed for survival outcomes for up to 2 years. Follow-up procedures are to be captured under the PNOC COMP protocol. Participants will be followed under the Pediatric Neuro-Oncology Consortium (PNOC) COMP protocol until death or withdrawal from study.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: PNOC Operations Office
  • Phone Number: 415-502-1600
  • Email: PNOC031@ucsf.edu

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
        • Contact:
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Principal Investigator:
          • Sabine Mueller, MD, PhD, MAS
        • Contact:
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Riley Hospital for Children at Indiana University Health
        • Contact:
        • Contact:
          • Alex Lion, DO
          • Phone Number: 317-944-8784
          • Email: alion@iu.edu
    • Maryland
      • Baltimore, Maryland, United States, 21218
        • Recruiting
        • Johns Hopkins University
        • Contact:
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Recruiting
        • Washington University in St. Louis
        • Contact:
        • Contact:
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
    • Tennessee
      • Memphis, Tennessee, United States, 38105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

The eligibility criteria listed below are interpreted literally and cannot be waived.

Inclusion Criteria:

  1. Participants must have either a molecularly or histologically confirmed embryonal tumor with multilayered rosettes.
  2. For enrollment, a confirmation of a minimum of 10-20 unstained formalin-fixed paraffin-embedded (FFPE) slides or 1 block (15-20 mg) with tumor content of 40% or greater is required. Anything less must be discussed and approved by the study chairs prior to enrollment.

  3. Prior Therapy:

    1. Cohort 1 participants must not have received any prior tumor-directed therapy other than surgical resection.
    2. Cohort 2 and 3 participants may receive tumor-directed therapy prior to enrollment. These participants must be discussed with study chairs prior to enrollment.
  4. Participants must not have received prior radiation for treatment of tumor.
  5. Participants of any age are eligible.
  6. Participants should begin induction chemotherapy within 28 days of the most recent definitive surgical procedure. Participants beginning therapy beyond 28 days from surgery, will need to discuss with study chairs.

  7. Cohort specific eligibility

    1. Cohort 1: Gross-total resection, Eligible for early radiotherapy (please see age criteria below), and no evidence of metastatic disease.
    2. Cohort 2: Gross-total resection, high dose chemotherapy (please see age criteria below), and no evidence of metastatic disease.
    3. Cohort 3A: Metastatic or residual disease, and early radiotherapy.
    4. Cohort 3B: Metastatic or residual disease, and high dose chemotherapy.
    5. Radiotherapy Age Criteria (at the time of planned radiation): >12 months of age for participants with infratentorial tumor OR >15 months of age for participants with supratentorial tumor. For participants being treated on radiotherapy-containing arms, the legal parent/guardian or patient and the physician must be willing to allow the use of radiotherapy for treatment.
  8. Performance Score: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants <=16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

  9. Organ Function Requirements:

    1. Peripheral absolute neutrophil count (ANC) > 75,000/mm3
    2. Platelet count > 75,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 72 hours prior to enrollment).

  10. Adequate Renal Function defined as:

    a. Serum creatinine < 1.5 x upper limit normal (ULN) based on age and gender.

  11. Adequate Liver Function defined as:

    1. Total bilirubin < 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin < 3 x ULN or direct bilirubin < 1.5 x ULN,
    2. alanine aminotransferase (ALT) < 3 x ULN,
    3. aspartate aminotransferase (AST) < 3 x ULN,

  12. Adequate Neurologic Function defined as:

    a. Participants with seizure disorder may be enrolled if well controlled. Participants on enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drugs.

  13. As chemotherapeutic agents used in this trial are known to be teratogenic, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of study therapy. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  14. Participants must be enrolled on PNOC COMP prior to enrollment on PNOC031 if PNOC COMP is open to accrual at the enrolling institution.
  15. A legal parent/guardian or patient must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.

Exclusion Criteria

  1. Cohort 1 only: Participants who have received any prior tumor-directed therapy other than surgical intervention
  2. Participants who are receiving any other tumor directed investigational agents.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in study.
  4. Uncontrolled intercurrent illness.
  5. Women of childbearing potential must not be pregnant or breast-feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: Gross-total resection, non-metastatic, early radiotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 2 years.
Radiation: Radiotherapy (RT)
Undergo RT
Other Names:
  • Radiation Therapy
  • Focal Radiotherapy
Drug: Chemotherapy Drug, Cancer - Physician's Choice
One or more of the following may be assigned by the physician (physician's choice) per standard of care guidelines upon study enrollment following surgery: Cytarabine, Carboplatin, Cisplatin, Vincristine Sulfate injection (Vincristine PFS), Topotecan Hydrochloride, Dactinomycin, Thiotepa, Filgrastim, Cyclophosphamide, or Doxorubicin Hydrochloride. Not all participants will receive all possible drug regimens.
Other Names:
  • Standard of Care, High dose Chemotherapy
Procedure: Non-Investigational Surgical Resection
Undergo surgery directly before study enrollment as part of planned care.
Other Names:
  • Standard of Care Surgical Resection
  • Standard of Care Surgical Resection of Tumor
Drug: Temozolomide
Participants assigned to or whom receive optional RT will receive concurrent temozolomide
Other Names:
  • Temodar
Procedure: Tumor Tissue Sample
Tumor tissue will be collected for correlative studies
Other Names:
  • Tumor Specimen
Procedure: Blood Sample
Blood samples will be collected for correlative studies
Other Names:
  • Blood Specimen
Procedure: Cerebrospinal Fluid (CSF) Sample
CSF samples will be collected for correlative studies
Other Names:
  • CSF Specimen
Experimental: Cohort 2: Gross-total resection, non-metastatic, high-dose chemotherapy
Participants will undergo gross total resection of the tumor prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 2 years.
Radiation: Radiotherapy (RT)
Undergo RT
Other Names:
  • Radiation Therapy
  • Focal Radiotherapy
Drug: Chemotherapy Drug, Cancer - Physician's Choice
One or more of the following may be assigned by the physician (physician's choice) per standard of care guidelines upon study enrollment following surgery: Cytarabine, Carboplatin, Cisplatin, Vincristine Sulfate injection (Vincristine PFS), Topotecan Hydrochloride, Dactinomycin, Thiotepa, Filgrastim, Cyclophosphamide, or Doxorubicin Hydrochloride. Not all participants will receive all possible drug regimens.
Other Names:
  • Standard of Care, High dose Chemotherapy
Procedure: Non-Investigational Surgical Resection
Undergo surgery directly before study enrollment as part of planned care.
Other Names:
  • Standard of Care Surgical Resection
  • Standard of Care Surgical Resection of Tumor
Drug: Temozolomide
Participants assigned to or whom receive optional RT will receive concurrent temozolomide
Other Names:
  • Temodar
Procedure: Tumor Tissue Sample
Tumor tissue will be collected for correlative studies
Other Names:
  • Tumor Specimen
Procedure: Blood Sample
Blood samples will be collected for correlative studies
Other Names:
  • Blood Specimen
Procedure: Cerebrospinal Fluid (CSF) Sample
CSF samples will be collected for correlative studies
Other Names:
  • CSF Specimen
Experimental: Cohort 3A: Metastatic or residual disease, early radiotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort will receive standard dose induction chemotherapy and 6-weeks of early focal radiotherapy, followed by and a second standard dose induction chemotherapy for a total of 12 weeks of chemotherapy; 18 weeks of treatments in all. Participants will be followed for up to 5 years.
Radiation: Radiotherapy (RT)
Undergo RT
Other Names:
  • Radiation Therapy
  • Focal Radiotherapy
Drug: Chemotherapy Drug, Cancer - Physician's Choice
One or more of the following may be assigned by the physician (physician's choice) per standard of care guidelines upon study enrollment following surgery: Cytarabine, Carboplatin, Cisplatin, Vincristine Sulfate injection (Vincristine PFS), Topotecan Hydrochloride, Dactinomycin, Thiotepa, Filgrastim, Cyclophosphamide, or Doxorubicin Hydrochloride. Not all participants will receive all possible drug regimens.
Other Names:
  • Standard of Care, High dose Chemotherapy
Procedure: Non-Investigational Surgical Resection
Undergo surgery directly before study enrollment as part of planned care.
Other Names:
  • Standard of Care Surgical Resection
  • Standard of Care Surgical Resection of Tumor
Drug: Temozolomide
Participants assigned to or whom receive optional RT will receive concurrent temozolomide
Other Names:
  • Temodar
Procedure: Tumor Tissue Sample
Tumor tissue will be collected for correlative studies
Other Names:
  • Tumor Specimen
Procedure: Blood Sample
Blood samples will be collected for correlative studies
Other Names:
  • Blood Specimen
Procedure: Cerebrospinal Fluid (CSF) Sample
CSF samples will be collected for correlative studies
Other Names:
  • CSF Specimen
Experimental: Cohort 3B: Metastatic or residual disease, high-dose chemotherapy
Participants metastatic disease or residual disease following their initial surgical interventions prior to enrollment into this cohort. Participants will receive 6 weeks of induction chemotherapy and 3 cycles (approximately 4 weeks each) of high-dose chemotherapy with stem cell rescue and will have the option to receive radiotherapy at the completion of therapy, for a total of 18-24 weeks. Participants will be followed for up to 5 years.
Radiation: Radiotherapy (RT)
Undergo RT
Other Names:
  • Radiation Therapy
  • Focal Radiotherapy
Drug: Chemotherapy Drug, Cancer - Physician's Choice
One or more of the following may be assigned by the physician (physician's choice) per standard of care guidelines upon study enrollment following surgery: Cytarabine, Carboplatin, Cisplatin, Vincristine Sulfate injection (Vincristine PFS), Topotecan Hydrochloride, Dactinomycin, Thiotepa, Filgrastim, Cyclophosphamide, or Doxorubicin Hydrochloride. Not all participants will receive all possible drug regimens.
Other Names:
  • Standard of Care, High dose Chemotherapy
Procedure: Non-Investigational Surgical Resection
Undergo surgery directly before study enrollment as part of planned care.
Other Names:
  • Standard of Care Surgical Resection
  • Standard of Care Surgical Resection of Tumor
Drug: Temozolomide
Participants assigned to or whom receive optional RT will receive concurrent temozolomide
Other Names:
  • Temodar
Procedure: Tumor Tissue Sample
Tumor tissue will be collected for correlative studies
Other Names:
  • Tumor Specimen
Procedure: Blood Sample
Blood samples will be collected for correlative studies
Other Names:
  • Blood Specimen
Procedure: Cerebrospinal Fluid (CSF) Sample
CSF samples will be collected for correlative studies
Other Names:
  • CSF Specimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free survival at 6 months (PFS6) (Cohort 1)
Time Frame: Up to 6 months
The median PFS6 is defined as the median number of months for participants in Cohort 1 who have remained progression-free from the date of initial surgical resection until 6 months.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free survival at 2 years progression-free survival (PFS)
Time Frame: Up to 2 years
The median PFS6 is defined as the median number of months for participants by cohort who have remained progression-free from the date of initial surgical resection until 2 years post-surgery.
Up to 2 years
Median Overall Survival at 2 years (OS)
Time Frame: Up to 2 years
The median OS is defined as the median number of months for participants by cohort who are still alive from the date of initial surgical resection until 2 years post-surgery.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Solving Kids' Cancer
Pediatric Neuro-Oncology Consortium

Investigators

  • Principal Investigator: Sabine Mueller, MD, PhD, MAS, University of California, San Francisco
  • Study Chair: Derek Hanson, MD, Hackensack Meridian Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 6, 2025

Primary Completion (Estimated)

September 30, 2030

Study Completion (Estimated)

March 31, 2032

Study Registration Dates

First Submitted

February 28, 2025

First Submitted That Met QC Criteria

February 28, 2025

First Posted (Actual)

March 6, 2025

Study Record Updates

Last Update Posted (Actual)

April 23, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 240830
  • NCI-2025-01764 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data may be shared with study collaborators

IPD Sharing Time Frame

Until study close out

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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