Pilot Study of IT Topotecan and Maintenance Chemotherapy for HR-EBTs in Children < 6 Years, Post Consolidation

NCT06942039 | Recruiting Early Phase 1

• 1 other identifier: DECRYPT-BABYBRAIN
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

CNS Embryonal Tumor; CNS, Medulloblastoma; Atypical Teratoid Rhabdoid Tumor; Medulloblastoma, Childhood; Medulloblastoma, Group 3; Medulloblastoma, Group 4; Pineoblastoma; Neuroblastoma; Embryonal Tumor With Multilayered Rosettes; Embryonal Tumor With Abundant Neuropil and True Rosettes; Ependymoblastoma; Medulloepithelioma; CNS Embryonal Tumor With Rhabdoid Features; CNS Embryonal Tumor, Nos

Keywords

HR-EBT

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  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

  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

  30 days after last dose of study treatment

Other Outcomes (1)

• To test the feasibility of prospective banking of tumor tissue, serial plasma and cerebrospinal fluid (CSF) for all enrolled patients

  Through completion of study treatment (anticipated duration of 18-24 months per participant)

Study Arms (1)

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.

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

Interventions

hydrocortisone DRUG

Double IT therapy (cytarabine, hydrocortisone) during induction (3 cycles, 1 cycle = 21 days) alongside CISplatin, vinCRIStine, etoposide, cyclophosphamide, mesna and filgrastim (G-CSF).

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Cisplatin DRUG

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).

Also known as: CDDP

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Vincristine DRUG

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).

Also known as: VCR

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Etoposide DRUG

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.

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Mesna DRUG

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).

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Filgrastim DRUG

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.

Also known as: G-CSF

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

carboplatin DRUG

Consolidation: Intravenous Carboplatin given on days -3 \& -2 during consolidation alongside thiotepa and filgrastim.

Also known as: CARBO

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Thiotepa DRUG

Consolidation: Intravenous Thiotepa given on days -3 \& -2 during consolidation alongside carboplatin and filgrastim.

Also known as: THIO

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Topotecan IT DRUG

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.

Also known as: Intrathecal Topotecan

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Tamoxifen DRUG

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.

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

ISOtretinoin DRUG

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.

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Celecoxib DRUG

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.

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

etoposide phosphate DRUG

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.

Also known as: Etopophos

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Temozolomide DRUG

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.

Also known as: TMZ

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Cytarabine IT DRUG

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).

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Cyclophosphamide DRUG

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.

Also known as: CPM

Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• C17 Council: lead

Study Sites (12)

Alberta Children's Hospital

Calgary, Alberta, Canada

RECRUITING

BC Children's Hospital

Vancouver, British Columbia, Canada

RECRUITING

CancerCare Manitoba (CCMB)

Winnipeg, Manitoba, Canada

NOT YET RECRUITING

IWK Health Centre

Halifax, Nova Scotia, Canada

NOT YET RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, Canada

NOT YET RECRUITING

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

CHU Sainte-Justine

Montreal, Quebec, Canada

RECRUITING

Montreal Children's Hospital (McGill)

Montreal, Quebec, Canada

NOT YET RECRUITING

CHU de Québec-Université Laval

Québec, Quebec, Canada

NOT YET RECRUITING

Centre hospitalier universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, Canada

NOT YET RECRUITING

Stollery Children's Hospital

Edmonton, Canada

NOT YET RECRUITING

The Hospital for Sick Children

Toronto, Canada

RECRUITING

MeSH Terms

Conditions

Medulloblastoma; Rhabdoid Tumor; Pinealoma; Neuroblastoma; Neuroectodermal Tumors, Primitive; Pyloric Stenosis, Hypertrophic

Interventions

Hydrocortisone; Cisplatin; Vincristine; Etoposide; Cyclophosphamide; Mesna; Filgrastim; Granulocyte Colony-Stimulating Factor; Carboplatin; Thiotepa; Tamoxifen; Isotretinoin; Celecoxib; etoposide phosphate; Temozolomide

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Coordination Complexes; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Retinoids; Carotenoids; Polyenes; Alkenes; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Terpenes; Pigments, Biological; Benzenesulfonamides; Sulfonamides; Amides; Sulfones; Pyrazoles; Azoles; Dacarbazine; Triazenes; Imidazoles

Study Officials

• Sylvia Cheng

  BC Cancer Centre

  STUDY CHAIR

• Annie Huang

  The Hospital for Sick Children

  STUDY CHAIR

• Lucie Lafay-Cousin

  Alberta Children's Hospital

  STUDY CHAIR

Central Study Contacts

Sylvia Cheng

CONTACT

416-813-7654; sylvia.cheng@cw.bc.ca

C17 Council

CONTACT

DECRYPT-BABYBRAIN@C17.ca

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: April 24, 2025
• Study Start: September 23, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2032
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

CA (12)