Testing Safe Doses of Anti-Cancer Medicines, 5-Flurouracil (5-FU) and Tretinoin (ATRA), Added to the Usual Cancer Treatment of Ependymoma

NCT07848568 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: ACNS2422NCI-2026-06714U10CA180886
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial tests the safety, side effects best dose and how well giving fluorouracil and tretinoin along with standard of care radiation therapy works for the treatment of high risk posterior fossa ependymoma that has not spread to other parts of the body (localized). Fluorouracil is a type medication called an antimetabolite. It works by stopping cells from making DNA and it may kill tumor cells. Tretinoin, also called all-trans retinoic acid (ATRA), retinoic acid, and vitamin A acid is in a class of medications called retinoids. It is made in the body from vitamin A and helps cells to grow and develop, especially in the embryo. Laboratory made form of tretinoin works by slowing or stopping the growth of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Giving fluorouracil and tretinoin along with standard of care radiation therapy may be safe, tolerable and/or effective in treating patients with localized high risk posterior fossa ependymoma.

Conditions

Childhood Posterior Fossa Ependymoma

Outcome Measures

Primary Outcomes (3)

• Occurrence of dose limiting toxicity chemoradiotherapy (DLT) (phase 1)

  Will report the sample proportion of analysis patients experiencing DLTs with binominal exact 95% confidence intervals by dose level. Other toxicity data will also be described as appropriate for supportive analyses.

  From the start of chemoradiotherapy until 4 weeks after completing chemoradiotherapy

• Occurrence of DLT for maintenance therapy (phase 1)

  Will report the sample proportion of analysis patients experiencing DLTs with binominal exact 95% confidence intervals by dose level. Other toxicity data will also be described as appropriate for supportive analyses. A planned supportive analysis will descriptively assess any interaction between increasing chemoradiotherapy dose and maintenance therapy tolerability.

  From the start of the first maintenance therapy cycle until the end of the first maintenance therapy cycle (Cycle = 42 days)

• Event free survival (EFS)

  Will test whether the EFS in the prospective patients is superior to the historical control using a stratified log-rank test adjusting for resection status (subtotal resection \[STR\] or gross total resection/near total resection GTR/NTR\]) with a one-sided type-1 error rate of 0.10. The primary analysis will also report the Kaplan-Meier estimates of the prospective and historical control patients. Planned supportive analyses will assess whether EFS differs by resection status within the prospective patients, and conduct separate resection status-specific comparisons between the prospective and corresponding historical control patients. These analyses will use unadjusted log-rank tests.

  From enrollment to the first of any of the following events: disease progression, disease recurrence, second malignant neoplasm, or death from any cause, up to 5 years

Secondary Outcomes (2)

• Overall response

  After completing chemoradiotherapy (up to 49 days) and after completing maintenance therapy (Up to 6 cycles (Cycle= 42 days))

• Overall survival

  From enrollment to death from any cause, up to 5 years

Other Outcomes (6)

• Correlate presence of tumor cell free deoxyribonucleic acid (DNA) with methylation profiling and clinical outcome

  Up to 5 years

• Correlate histopathologic grade with clinical outcome

  Up to 5 years

• Correlate gene expression profiles with clinical outcome

  Up to 5 years

Study Arms (1)

Treatment (radiation, fluorouracil, tretinoin)

EXPERIMENTAL

CHEMORADIOTHERAPY: Patients receive standard of care radiation therapy over 6 or 7 weeks. Starting on day 1, 2 or 3 of radiation, patients receive fluorouracil IV over 3-15 minutes on days 1 and 15, days 1, 8 and 15, or days 1, 8, 15 and 22 depending upon assigned dose level. Treatment is given in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMOTHERAPY: Four weeks after completion of chemoradiotherapy, patients receive fluorouracil IV on days 1, 8, 15 and 22 of each cycle and tretinoin PO TID on days 1-3, 8-10, 15-17 and 22-24 of each cycle. Cycles repeat every 42 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA, MRI, lumbar puncture, and optional blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Echocardiography Test; Drug: Fluorouracil; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Radiation: Radiation Therapy; Drug: Tretinoin

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and CSF sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (radiation, fluorouracil, tretinoin)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (radiation, fluorouracil, tretinoin)

Fluorouracil DRUG

Given IV

Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (radiation, fluorouracil, tretinoin)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Treatment (radiation, fluorouracil, tretinoin)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (radiation, fluorouracil, tretinoin)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (radiation, fluorouracil, tretinoin)

Radiation Therapy RADIATION

Undergo standard of care radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (radiation, fluorouracil, tretinoin)

Tretinoin DRUG

Given PO

Also known as: 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten, all trans-Retinoic acid, All-trans Retinoic Acid, All-trans Vitamin A Acid, all-trans-Retinoic acid, all-trans-Vitamin A acid, ATRA, Avita, beta-Retinoic Acid, Cordes Vas, Dermairol, Epi-Aberel, Eudyna, Renova, Retin-A, Retin-A MICRO, Retin-A-Micro, Retinoic Acid, Retisol-A, Ro 5488, Stieva-A, Stieva-A Forte, Trans Retinoic Acid, Trans Vitamin A Acid, trans-Retinoic Acid, Tretinoinum, Vesanoid, Vitamin A Acid, Vitamin A acid, all-trans-, Vitinoin

Treatment (radiation, fluorouracil, tretinoin)

Eligibility Criteria

• Age: 12 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• PRE-ENROLLMENT: Patients must be \> 12 months and \< 21 years of age at the time of enrollment
• PRE-ENROLLMENT: Patient has newly diagnosed posterior fossa ependymoma based on institutional pathologic diagnosis
• PRE-ENROLLMENT: The patient and/or their parents or legal guardians must have signed informed consent for APEC14B1 Part A - Eligibility Screening
• PRE-ENROLLMENT: If relying on APEC14B1-MCI for molecular characterization, required specimens for molecular characterization should be submitted as soon as possible, preferably within 5 calendar days of definitive surgery
• Patients must be \> 12 months and \< 21 years at the time of study enrollment
• Patients must be newly diagnosed, localized and have eligibility confirmed by central review of molecular reports
• Histologically confirmed diagnosis of Posterior fossa ependymoma, group PFA
• Molecular high risk features including Chromosome 1q gain and/or chromosome 6q loss
• Patients must be enrolled on study within 56 days of definitive surgical resection. If applicable, the day of subsequent resection to remove residual tumor will be regarded as the day of definitive surgery and must be within a month (31 days) of the initial resection
• Patients must have negative lumbar CSF cytology.
• Note: CSF cytology for staging should be performed no sooner than 14 days post operatively to avoid false positive CSF. Ideally, CSF should be obtained between Day 14 and Day 21 to allow for final staging status before enrollment onto the study. Patients with positive lumbar CSF cytology obtained 0 to 14 days after surgery should have lumbar cytology repeated to determine eligibility and final CSF status. Patients with negative CSF lumbar cytology from lumbar puncture obtained 0 to 14 days after surgery do not need cytology repeated. Patients with negative CSF cytology from lumbar puncture obtained prior to surgery do not need cytology repeated post-operatively.
• CSF cytology does not need to be repeated if within 87 days prior to enrollment regardless of timing
• Patients must have localized disease. Pre and post-operative whole brain MRI with and without gadolinium and spine MRI with gadolinium must be performed
• Disease/staging imaging studies, including MRI brain (post operative) and spine (pre or post-operative), must be obtained within 31 days prior to enrollment and start of protocol therapy (repeat if necessary)
• No prior treatment other than surgical intervention and corticosteroids. Patients are allowed to have had more than one surgical resection prior to enrollment. For patients who have subsequent surgery, the day of the subsequent resection to remove residual tumor will be regarded as the day of definitive surgery and must be within a month (31 days) of initial resection

You may not qualify if:

• Patients with metastatic disease by either MRI evaluation or lumbar CSF cytology are not eligible. Patients who are unable to undergo a lumbar puncture for assessment of CSF cytology are ineligible
• Hypersensitivity to fluorouracil, tretinoin, other retinoids, or any component of the formulation
• Personal history of Torsades de pointes, atrial fibrillation, supraventricular tachycardia (SVT), or heart failure; personal history of prolonged QT Syndrome; other uncontrolled arrhythmia in the past 6 months prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation. Patients who could become pregnant should use effective contraception during treatment and 1 month following the last dose of tretinoin or for 3 months following last dose of fluorouracil, whichever is longer. Patients with partners who could become pregnant should also use effective contraception during treatment and for 1 week after the last dose of tretinoin or 3 months after the last dose of fluorouracil, whichever is longer

Sponsors & Collaborators

• Children's Oncology Group: lead

MeSH Terms

Interventions

Specimen Handling; Fluorouracil; dehydroftorafur; Spinal Puncture; Magnetic Resonance Spectroscopy; Radiotherapy; Radiation; Tretinoin

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Physical Phenomena; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Adam J Esbenshade

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 30, 2026
• Study Start (Estimated): December 11, 2026
• Primary Completion (Estimated): June 30, 2037
• Study Completion (Estimated): June 30, 2037
• Last Updated: September 30, 2026

Record last verified: 2026-09