CNS Embryonal TumorEarly Phase 1NCT06942039
Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation
A Early Phase 1 study testing Cytarabine IT, hydrocortisone and Cisplatin in people with CNS Embryonal Tumor and CNS, Medulloblastoma, run by C17 Council at 13 sites in Canada.
Trial summary
Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age. Read more about this study
- Who is it for?
- Ages Up to 6 years
- Conditions the study is for
- CNS Embryonal Tumor, CNS, Medulloblastoma, Atypical Teratoid Rhabdoid Tumor
- What is being tested?
- Cytarabine IT, hydrocortisone and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 13 sitesCanada
- Study dates
- 23 Sep 2025to 31 Dec 2032
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Tumor Tissue Sample
- Age: Patient must be aged ≥ 0 years to ≤ 6 years at the time of definitive confirmation of histologic diagnosis of eligible CNS tumor.
- Diagnoses. Participants must have Central nervous system (CNS) HR-EBT including atypical teratoid rhabdoid tumour (ATRT), group 3 and group 4 medulloblastoma (MB), pineoblastoma, CNS neuroblastoma, embryonal tumor with multi-layered rosettes (ETMR including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified. Metastatic disease included. Any extent of resection included.
- Cranial and Spine MRI. A baseline MRI brain and spine with and without contrast is required for all patients. cranial MRI (with and without gadolinium) must be done pre-operatively. Post-operatively, cranial MRI (with and without gadolinium) must be done.
- Lumbar Puncture (LP) CSF for cytopathology (strongly recommended but not mandatory; if medically feasible). A baseline LP CSF cytology either pre-operatively or post-operatively at least 10 days after definitive surgery for all patients if medically feasible (This is not mandatory and will not make the patient ineligible).
- Life expectancy: Patients must have a life expectancy of greater than 8 weeks from diagnosis.
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- Performance level: Patients must have a performance status corresponding of a Lansky score ≥ 50.
- Organ Function Requirements: Participants must have normal organ and marrow function as defined below:
- Adequate renal function defined as:
- Creatinine clearance (12-24-hour urine collection) or radioisotope glomerular filtration rate (GFR) ≥ 60 ml/min/1.73m2
- Adequate cardiac function defined as:
- Shortening fraction of ≥ 27% by echocardiogram, or
- Ejection fraction of ≥ 47% by radionuclide angiogram.
- Adequate pulmonary function defined as:
- No evidence of dyspnea at rest and a pulse oximetry > 94% on room air.
- Adequate Bone Marrow Function defined as:
- Peripheral absolute neutrophil count (ANC) > 1000/μL
- Platelet Count > 100,000/μL (without transfusion for 3 days)
- Hemoglobin greater than 8 gm/dL (may have received red blood cell (RBC) transfusions)
- Adequate liver function defined as:
- Total bilirubin ≤ 1.5X upper limit of normal (ULN) within normal institutional limits for age (patients with documented Gilbert's Disease may be enrolled with Study Chair approval and total bilirubin ≤ 2.0 × ULN)
- Alanine Aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 100 U/L
Who cannot join
- Patients who are receiving any other conventional anti-cancer agents or investigational agents.
- Patients who received previous therapy including radiotherapy or chemotherapy other than corticosteroids.
- Presence of another malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
- Concomitant medications restrictions: Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine), selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort or CYP450 3A4 stimulators or inhibitors.
- Other uncontrollable medical disease: Patient has a severe and uncontrollable medical disease (i.e., uncontrolled diabetes, hyperglycemia, chronic renal disease or active uncontrolled infection), has chronic liver disease (i.e., chronic active hepatitis and cirrhosis), hypercholesterolemia (serum cholesterol >300 mg/dL), intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hyperparathyroidism, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who have a known diagnosis of human immunodeficiency virus (HIV) infection, hepatitis B or C.
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- Ineligible diagnoses for study entry by neuropathology: This includes sonic hedgehog (SHH) and wingless (WNT) MBs, all ependymomas, all choroid plexus carcinomas, all high grade glial and glio-neuronal tumors, all diffuse midline gliomas, all primary CNS germ cell tumors, all primary CNS sarcomas, all primary or metastatic CNS lymphomas and solid leukemic lesions (chloromas, granulocytic sarcomas).
- The participant or parent(s)/guardian(s) cannot comply with the study visit schedule and other protocol requirements, in the investigator's opinion.
- All patients must meet inclusion/exclusion criteria prior to starting any protocol therapy.
Trial locations and contacts
13 sites in 1 country. Contact the study team or a site near you to ask about taking part.
C17 Council contact
13 sites in 1 country
Canada13 sites, 13 recruiting
- Recruiting
Alberta Children's Hospital
Calgary, Alberta
Oluwatosin Ogunleye, Oluwatosin.Ogunleye@albertahealthservices.ca
Lucie Lafay-Cousin, lucie.lafay-cousin@albertahealthservices.ca
- Recruiting
Stollery Children's Hospital
Edmonton
Guru Piragasam, Guru.Piragasam@albertahealthservices.ca
Liana Nobre
- Not yet recruiting
IWK Health Centre
Halifax, Nova Scotia
Tiffany Rent, Tiffany.Rent@iwk.nshealth.ca
Bruce Crooks
- Recruiting
McMaster Children's Hospital
Hamilton, Ontario
Shawde Campbell, campshaw@HHSC.CA
Adam Fleming
- Recruiting
London Health Sciences Centre
London, Ontario
Jessica Kuzyk, jessica.kuzyk@lhsc.on.ca
Shayna Zelcer
- Recruiting
CHU Sainte-Justine
Montreal, Quebec
Caroline Tra, caroline.tra.hsj@ssss.gouv.qc.ca
Sebastien Perreault
- Recruiting
Montreal Children's Hospital (McGill)
Montreal, Quebec
Poshia Boateng, poshia.boateng@muhc.mcgill.ca
Christina Coleman
- Recruiting
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Doaa Abdelfattah, 613-737-7600, DAbdelfattah@cheo.on.ca
Donna Johnston
- Recruiting
CHU de Québec-Université Laval
Québec, Quebec
Panagiota Giannakouros, Panagiota.Giannak@crchudequebec.ulaval.ca
Samuele Renzi
- Recruiting
Centre hospitalier universitaire de Sherbrooke (CHUS)
Sherbrooke, Quebec
Alexis Gonneaud, alexis.gonneaud.ciussse-chus@ssss.gouv.qc.ca
Stephanie Vairy
- Recruiting
The Hospital for Sick Children
Toronto
Grace Silver, grace.silver@sickkids.ca
Anthony Liu
- Recruiting
BC Children's Hospital
Vancouver, British Columbia
Sofie Jensen, sofie.jensen@cw.bc.ca
George Michaiel
- Recruiting
CancerCare Manitoba (CCMB)
Winnipeg, Manitoba
Divya Subburaj, MD, 204-787-4156, ctu_web@cancercare.mb.ca
Divya Subburaj
About this study
Official title: A Pilot Study of Intrathecal Topotecan and Maintenance Chemotherapy in the Post-consolidation Setting for the Treatment of High-risk Embryonal Central Nervous System Tumours in Children Less Than 6 Years of Age
Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.
Read the detailed description
This is a pilot study to determine feasibility of adding intrathecal (IT) chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age. Patients meeting all inclusion criteria will receive 3 cycles of multiagent chemotherapy induction (vinCRIStine, cyclophosphamide, CISplatin, etoposide) with IT cytarabine and hydrocortisone, and 3 cycles of consolidation with CARBOplatin, thiotepa, and autologous stem cell rescue (as per CCG 99703). Maintenance chemotherapy will then be given immediately after the completion of consolidation therapy and consist of risk-stratified oral chemotherapy using either "Maintenance A" (48 weeks) using tamoxifen and retinoic acid or "Maintenance B" (54 weeks) using metronomic isotretinoin, celecoxib, etoposide, temozolomide, and cyclophosphamide. Both arms of maintenance will receive monthly IT topotecan.
Following the end of treatment, patients will be scheduled for a follow-up visit every 3 months for 24 months to evaluate PFS and OS. Approximately 15 patients will be recruited as part of this clinical study.
Patients aged between 0 and 6 years old at the time of enrollment will be eligible. This study will only enrol patients with high risk Central Nervous System Embryonal Brain Tumors (CNS-EBTs) with histologic and/or molecular confirmation of diagnosis for ATRT intrinsic to the brain and spinal cord, group 3 and group 4 MB, pineoblastoma, CNS neuroblastoma, ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified.
Response to treatment will be evaluated using the modified RAPNO (Response Assessment in Pediatric Neuro-Oncology) 1.
This study will also explore the genetic landscape of CNS HR-EBTs. Our biological study will include genomic analyses of tumor and CSF with use of epigenomic analyses (methylation profiling) arrays, Nanostring sub-typing studies, Next generation sequencing analyses for DNA and/or RNA.
- Conditions
- CNS Embryonal Tumor, CNS, Medulloblastoma, Atypical Teratoid Rhabdoid Tumor, Medulloblastoma, Childhood, Medulloblastoma, Group 3, Medulloblastoma, Group 4
- Being tested
- Cytarabine IT, hydrocortisone, Cisplatin, Vincristine, Etoposide
- Keywords
- HR-EBT
- Medical subject headings
- Medulloblastoma, Rhabdoid Tumor, Pinealoma, Neuroblastoma, Neuroectodermal Tumors, Primitive, Pyloric Stenosis, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytarabine ITDrug
Age-based dosing as a part of double IT therapy (cytarabine, hydrocortisone) during induction (3 cycles, 1 cycle = 21 days) alongside CISplatin, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF).
hydrocortisoneDrug
Double IT therapy (cytarabine, hydrocortisone) during induction (3 cycles, 1 cycle = 21 days) alongside CISplatin, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF).
CisplatinDrug
Also called CDDP
Intravenous CISplatin given on Day 1 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF).
VincristineDrug
Also called VCR
Intravenous VinCRIStine given on Days 1, 8 \& 15 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF).
EtoposideDrug
Induction: Intravenous Etoposide given on Days 1, 2 \& 3 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, vinCRIStine, cyclophosphamide, mesna and filgrastim (G-CSF).
Maintenance Arm B (for high-risk patients): Oral Etoposide given on Days 1-21 every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) in combination with IT Topotecan, ISOtretinoin, Celecoxib, Cyclophosphamide and Temozolomide.
CyclophosphamideDrug
Also called CPM
Induction: Intravenous high-dose Cyclophosphamide given on Days 2 \& 3 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, vinCRIStine, etoposide, mesna and filgrastim (G-CSF).
Maintenance Arm B (for high-risk patients): Oral Cyclophosphamide given on Days 1-21 every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) in combination with IT Topotecan, ISOtretinoin, Celecoxib, Etoposide and Temozolomide.
MesnaDrug
Induction: Intravenous Mesna given at hour 0 of Cyclophosphamide delivery and 3, 6, 9 \& 12 hours post-dose during induction (3 cycles, 1 cycle = 21 days).
FilgrastimDrug
Also called G-CSF
Induction: Subcutaneous or intravenous Filgrastim (G-CSF) given 24-48 hrs after last dose of chemotherapy and/or as per institutional guidelines until count recovery.
Consolidation: Subcutaneous or intravenous Filgrastim (G-CSF) given 24-48 hours after last stem cell infusion and/or per institutional guidelienes until count recovery.
carboplatinDrug
Also called CARBO
Consolidation: Intravenous Carboplatin given on days -3 \& -2 during consolidation alongside thiotepa and filgrastim.
ThiotepaDrug
Also called THIO
Consolidation: Intravenous Thiotepa given on days -3 \& -2 during consolidation alongside carboplatin and filgrastim.
Topotecan ITDrug
Also called Intrathecal Topotecan
Maintenance A (for low-risk patients): IT Topotecan on Day 1 of each cycle (max 12 cycles, 1 cycle = 28 days) alongside Tamoxifen and ISOtretinoin.
Maintenance B (for high-risk patients): IT Topotecan every 4 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside ISOtretinoin, Celecoxib, Etoposide, Cyclophosphamide and Temozolomide.
TamoxifenDrug
Maintenance A (for low-risk patients): Oral Tamoxifen twice daily, Days 1-28 (max 12 cycles, 1 cycle = 28 days) alongside ISOtretinoin and IT Topotecan.
ISOtretinoinDrug
Maintenance A (for low-risk patients): Oral ISOtretinoin twice daily on Days 15-28 of each cycle (max 12 cycles, 1 cycle = 28 days) alongside Tamoxifen and IT Topotecan.
Maintenance B (for high-risk patients): Oral ISOtretinoin twice daily on Days 1-21, every 6 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, Celecoxib, Etoposide, Cyclophosphamide and Temozolomide.
CelecoxibDrug
Maintenance B (for high-risk patients): Oral Celecoxib twice daily on Days 1-21, every 6 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, ISOtretinoin, Etoposide, Cyclophosphamide and Temozolomide.
etoposide phosphateDrug
Also called Etopophos
During Induction and Maintenance B (for high-risk patients), etoposide phosphate may be given for subsequent doses to patients who have experienced etoposide allergic reactions.
TemozolomideDrug
Also called TMZ
Maintenance B (for high-risk patients): Oral Temozolomide daily on Days 1-21, every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, ISOtretinoin, Etoposide, Cyclophosphamide and Celecoxib.
| Study group | Role | What they receive |
|---|---|---|
| Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance | Experimental | Participants will undergo a comprehensive treatment regimen beginning with three 21-day cycles of Induction chemotherapy including intrathecal (IT) cytarabine with hydrocortisone, cyclophosphamide, etoposide, vinCRIStine, and cisplatin. Peripheral blood stem cells will be collected during this phase for later use. Patients who achieve complete response (CR) proceed directly to Consolidation; those who do not may undergo second-look surgery or national tumor board review.
Consolidation consists of three 28-day cycles of CARBOplatin and thiotepa followed by autologous stem cell rescue. Patients then proceed to up to 48-54 weeks of Maintenance chemotherapy based on risk stratification.
Low-risk patients receive monthly IT topotecan and a 28-day metronomic regimen including tamoxifen and ISOtretinoin.
High-risk patients receive monthly IT topotecan and a more intensive regimen every 9 weeks including ISOtretinoin, celecoxib, etoposide, cyclophosphamide, and temozolomide. Receives: Drug: Cytarabine IT; Drug: hydrocortisone; Drug: Cisplatin; Drug: Vincristine; Drug: Etoposide; Drug: Cyclophosphamide; Drug: Mesna; Drug: Filgrastim; Drug: carboplatin; Drug: Thiotepa; Drug: Topotecan IT; Drug: Tamoxifen; Drug: ISOtretinoin; Drug: Celecoxib; Drug: etoposide phosphate; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the feasibility of adding intrathecal (IT) topotecan and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.
Feasibility failure will be defined by ≥5 patients who stop maintenance therapy (all IT and oral agents) due to excessive toxicity, deemed attributable to maintenance therapy
Measured: At completion of maintenance therapy (approximately 48-54 weeks after start of maintenance therapy)
To test the feasibility of centralized diagnostics and national tumour board review for clinical management of HR-EBTs
Feasibility of centralized diagnostics will be defined as:
- 80% of patients will have central review and central molecular testing performed before timely start of therapy (~4 weeks post-surgery)
Feasibility of national tumour board review will be defined as:
- 80% of patients will be reviewed within treatment timeline of within ~4 weeks post-surgery
Measured: Within 4 weeks after definitive surgical resection, prior to start of induction chemotherapy
To establish a national HR infant brain tumor trial platform for future studies
Data will be gathered on whether platform is able to support future research projects, facilitate collaboration in Canada, and improve clinical outcomes for this population
Measured: At study completion (anticipated average duration of 2 years per participant)
Secondary outcomes (2)
To determine progression free and overall survival and patterns of failure for all enrolled patients
Time to progression (TTP), progression free survival (PFS) and overall survival (OS) up to two years following completion of treatment
Measured: Up to 24 months following completion of maintenance therapy
To describe the toxicities of adding intrathecal (IT) chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age
Incidence of grade ≥3 adverse events (AE) and serious adverse events (SAE) related to study treatment
Measured: 30 days after last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start23 Sep 2025
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CNS Embryonal TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All patients will receive 3 cycles of induction with IT chemotherapy and 3 cycles of consolidation therapy. Patients will then receive either Maintenance A or Maintenance B based on their risk profile.
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- C17 Council
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sylvia Cheng, Study chair, BC Cancer CentreAnnie Huang, Study chair, The Hospital for Sick ChildrenLucie Lafay-Cousin, Study chair, Alberta Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06942039
- Sponsor's protocol ID
- DECRYPT-BABYBRAIN
- Status last verified
- Oct 2026
- First submitted
- 9 Apr 2025
- Last updated
- 2 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Intrathecal Topotecan and Maintenance Chemotherapy in the Post-consolidation Setting for the Treatment of High-risk Embryonal Central Nervous System Tumours in Children Less Than 6 Years of Age
- ClinicalTrials.gov ID
- NCT06942039
- Acronym / sponsor ID
- DECRYPT-BABYBRAIN
- Conditions
- CNS Embryonal Tumor, CNS, Medulloblastoma, Atypical Teratoid Rhabdoid Tumor, Medulloblastoma, Childhood, Medulloblastoma, Group 3, Medulloblastoma, Group 4
- Keywords
- HR-EBT
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- C17 CouncilUniversity, hospital or other
- Study start
- 23 Sep 2025 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 24 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pilot study to determine feasibility of adding intrathecal chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.
Detailed description
This is a pilot study to determine feasibility of adding intrathecal (IT) chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age. Patients meeting all inclusion criteria will receive 3 cycles of multiagent chemotherapy induction (vinCRIStine, cyclophosphamide, CISplatin, etoposide) with IT cytarabine and hydrocortisone, and 3 cycles of consolidation with CARBOplatin, thiotepa, and autologous stem cell rescue (as per CCG 99703). Maintenance chemotherapy will then be given immediately after the completion of consolidation therapy and consist of risk-stratified oral chemotherapy using either "Maintenance A" (48 weeks) using tamoxifen and retinoic acid or "Maintenance B" (54 weeks) using metronomic isotretinoin, celecoxib, etoposide, temozolomide, and cyclophosphamide. Both arms of maintenance will receive monthly IT topotecan.
Following the end of treatment, patients will be scheduled for a follow-up visit every 3 months for 24 months to evaluate PFS and OS. Approximately 15 patients will be recruited as part of this clinical study.
Patients aged between 0 and 6 years old at the time of enrollment will be eligible. This study will only enrol patients with high risk Central Nervous System Embryonal Brain Tumors (CNS-EBTs) with histologic and/or molecular confirmation of diagnosis for ATRT intrinsic to the brain and spinal cord, group 3 and group 4 MB, pineoblastoma, CNS neuroblastoma, ETMR, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified.
Response to treatment will be evaluated using the modified RAPNO (Response Assessment in Pediatric Neuro-Oncology) 1.
This study will also explore the genetic landscape of CNS HR-EBTs. Our biological study will include genomic analyses of tumor and CSF with use of epigenomic analyses (methylation profiling) arrays, Nanostring sub-typing studies, Next generation sequencing analyses for DNA and/or RNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All patients will receive 3 cycles of induction with IT chemotherapy and 3 cycles of consolidation therapy. Patients will then receive either Maintenance A or Maintenance B based on their risk profile.
| Arm | Type | Receives |
|---|---|---|
| Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance | Experimental | Drug: Cytarabine IT, Drug: hydrocortisone, Drug: Cisplatin, Drug: Vincristine, Drug: Etoposide, Drug: Cyclophosphamide, Drug: Mesna, Drug: Filgrastim, Drug: carboplatin, Drug: Thiotepa, Drug: Topotecan IT, Drug: Tamoxifen, Drug: ISOtretinoin, Drug: Celecoxib, Drug: etoposide phosphate, Drug: TemozolomideParticipants will undergo a comprehensive treatment regimen beginning with three 21-day cycles of Induction chemotherapy including intrathecal (IT) cytarabine with hydrocortisone, cyclophosphamide, etoposide, vinCRIStine, and cisplatin. Peripheral blood stem cells will be collected during this phase for later use. Patients who achieve complete response (CR) proceed directly to Consolidation; those who do not may undergo second-look surgery or national tumor board review. Consolidation consists of three 28-day cycles of CARBOplatin and thiotepa followed by autologous stem cell rescue. Patients then proceed to up to 48-54 weeks of Maintenance chemotherapy based on risk stratification. Low-risk patients receive monthly IT topotecan and a 28-day metronomic regimen including tamoxifen and ISOtretinoin. High-risk patients receive monthly IT topotecan and a more intensive regimen every 9 weeks including ISOtretinoin, celecoxib, etoposide, cyclophosphamide, and temozolomide. |
Who may qualify
- Ages
- Up to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (22 listed)
- Tumor Tissue Sample
- Age: Patient must be aged ≥ 0 years to ≤ 6 years at the time of definitive confirmation of histologic diagnosis of eligible CNS tumor.
- Diagnoses. Participants must have Central nervous system (CNS) HR-EBT including atypical teratoid rhabdoid tumour (ATRT), group 3 and group 4 medulloblastoma (MB), pineoblastoma, CNS neuroblastoma, embryonal tumor with multi-layered rosettes (ETMR including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma and ETMR not otherwise specified), medulloepithelioma, CNS embryonal tumor with rhabdoid features (INI-1 intact) and CNS embryonal tumor, not otherwise specified. Metastatic disease included. Any extent of resection included.
- Cranial and Spine MRI. A baseline MRI brain and spine with and without contrast is required for all patients. cranial MRI (with and without gadolinium) must be done pre-operatively. Post-operatively, cranial MRI (with and without gadolinium) must be done.
- Lumbar Puncture (LP) CSF for cytopathology (strongly recommended but not mandatory; if medically feasible). A baseline LP CSF cytology either pre-operatively or post-operatively at least 10 days after definitive surgery for all patients if medically feasible (This is not mandatory and will not make the patient ineligible).
Key exclusion criteria (9 listed)
- Patients who are receiving any other conventional anti-cancer agents or investigational agents.
- Patients who received previous therapy including radiotherapy or chemotherapy other than corticosteroids.
- Presence of another malignancy, except if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
- Concomitant medications restrictions: Concurrent use of enzyme inducing anticonvulsants (e.g. phenytoin, phenobarbital, and carbamazepine), selected strong inhibitors of cytochrome P450 3A4 include azole antifungals, such as fluconazole, voriconazole, itraconazole, ketoconazole, and strong inducers include drugs such as rifampin, phenytoin, phenobarbitol, carbamazepine, and St. John's wort or CYP450 3A4 stimulators or inhibitors.
- Other uncontrollable medical disease: Patient has a severe and uncontrollable medical disease (i.e., uncontrolled diabetes, hyperglycemia, chronic renal disease or active uncontrolled infection), has chronic liver disease (i.e., chronic active hepatitis and cirrhosis), hypercholesterolemia (serum cholesterol >300 mg/dL), intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active hyperparathyroidism, or psychiatric illness/social situations that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytarabine ITAge-based dosing as a part of double IT therapy (cytarabine, hydrocortisone) during induction (3 cycles, 1 cycle = 21 days) alongside CISplatin, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF). | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| hydrocortisoneDouble IT therapy (cytarabine, hydrocortisone) during induction (3 cycles, 1 cycle = 21 days) alongside CISplatin, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF). | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| CisplatinAlso: CDDPIntravenous CISplatin given on Day 1 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF). | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| VincristineAlso: VCRIntravenous VinCRIStine given on Days 1, 8 \& 15 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF). | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| EtoposideInduction: Intravenous Etoposide given on Days 1, 2 \& 3 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, vinCRIStine, cyclophosphamide, mesna and filgrastim (G-CSF). Maintenance Arm B (for high-risk patients): Oral Etoposide given on Days 1-21 every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) in combination with IT Topotecan, ISOtretinoin, Celecoxib, Cyclophosphamide and Temozolomide. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| CyclophosphamideAlso: CPMInduction: Intravenous high-dose Cyclophosphamide given on Days 2 \& 3 during induction (3 cycles, 1 cycle = 21 days) alongside double IT therapy, CISplatin, vinCRIStine, etoposide, mesna and filgrastim (G-CSF). Maintenance Arm B (for high-risk patients): Oral Cyclophosphamide given on Days 1-21 every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) in combination with IT Topotecan, ISOtretinoin, Celecoxib, Etoposide and Temozolomide. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| MesnaInduction: Intravenous Mesna given at hour 0 of Cyclophosphamide delivery and 3, 6, 9 \& 12 hours post-dose during induction (3 cycles, 1 cycle = 21 days). | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| FilgrastimAlso: G-CSFInduction: Subcutaneous or intravenous Filgrastim (G-CSF) given 24-48 hrs after last dose of chemotherapy and/or as per institutional guidelines until count recovery. Consolidation: Subcutaneous or intravenous Filgrastim (G-CSF) given 24-48 hours after last stem cell infusion and/or per institutional guidelienes until count recovery. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| carboplatinAlso: CARBOConsolidation: Intravenous Carboplatin given on days -3 \& -2 during consolidation alongside thiotepa and filgrastim. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| ThiotepaAlso: THIOConsolidation: Intravenous Thiotepa given on days -3 \& -2 during consolidation alongside carboplatin and filgrastim. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| Topotecan ITAlso: Intrathecal TopotecanMaintenance A (for low-risk patients): IT Topotecan on Day 1 of each cycle (max 12 cycles, 1 cycle = 28 days) alongside Tamoxifen and ISOtretinoin. Maintenance B (for high-risk patients): IT Topotecan every 4 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside ISOtretinoin, Celecoxib, Etoposide, Cyclophosphamide and Temozolomide. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| TamoxifenMaintenance A (for low-risk patients): Oral Tamoxifen twice daily, Days 1-28 (max 12 cycles, 1 cycle = 28 days) alongside ISOtretinoin and IT Topotecan. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| ISOtretinoinMaintenance A (for low-risk patients): Oral ISOtretinoin twice daily on Days 15-28 of each cycle (max 12 cycles, 1 cycle = 28 days) alongside Tamoxifen and IT Topotecan. Maintenance B (for high-risk patients): Oral ISOtretinoin twice daily on Days 1-21, every 6 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, Celecoxib, Etoposide, Cyclophosphamide and Temozolomide. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| CelecoxibMaintenance B (for high-risk patients): Oral Celecoxib twice daily on Days 1-21, every 6 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, ISOtretinoin, Etoposide, Cyclophosphamide and Temozolomide. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| etoposide phosphateAlso: EtopophosDuring Induction and Maintenance B (for high-risk patients), etoposide phosphate may be given for subsequent doses to patients who have experienced etoposide allergic reactions. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
| TemozolomideAlso: TMZMaintenance B (for high-risk patients): Oral Temozolomide daily on Days 1-21, every 9 weeks (max 6 cycles, 1 cycle = 9 weeks) alongside IT Topotecan, ISOtretinoin, Etoposide, Cyclophosphamide and Celecoxib. | Drug | Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance |
Primary outcome
To determine the feasibility of adding intrathecal (IT) topotecan and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age.
Time frame: At completion of maintenance therapy (approximately 48-54 weeks after start of maintenance therapy)
Feasibility failure will be defined by ≥5 patients who stop maintenance therapy (all IT and oral agents) due to excessive toxicity, deemed attributable to maintenance therapy
To test the feasibility of centralized diagnostics and national tumour board review for clinical management of HR-EBTs
Time frame: Within 4 weeks after definitive surgical resection, prior to start of induction chemotherapy
Feasibility of centralized diagnostics will be defined as: * 80% of patients will have central review and central molecular testing performed before timely start of therapy (~4 weeks post-surgery) Feasibility of national tumour board review will be defined as: * 80% of patients will be reviewed within treatment timeline of within ~4 weeks post-surgery
To establish a national HR infant brain tumor trial platform for future studies
Time frame: At study completion (anticipated average duration of 2 years per participant)
Data will be gathered on whether platform is able to support future research projects, facilitate collaboration in Canada, and improve clinical outcomes for this population
2 secondary outcomes
To determine progression free and overall survival and patterns of failure for all enrolled patients
Time frame: Up to 24 months following completion of maintenance therapy
To describe the toxicities of adding intrathecal (IT) chemotherapy and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age
Time frame: 30 days after last dose of study treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
C17 Council contact
Sylvia Cheng study chair
BC Cancer Centre
Annie Huang study chair
The Hospital for Sick Children
Lucie Lafay-Cousin study chair
Alberta Children's Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Cytarabine IT, hydrocortisone and Cisplatin in people with CNS Embryonal Tumor and CNS, Medulloblastoma, run by C17 Council at 13 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sylvia Cheng (416-813-7654 ext. 414839, sylvia.cheng@cw.bc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the feasibility of adding intrathecal (IT) topotecan and maintenance therapy after high dose chemotherapy for treatment of newly diagnosed HR-EBTs in patients less than 6 years of age. (time frame: At completion of maintenance therapy (approximately 48-54 weeks after start of maintenance therapy)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.