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

Sponsor
C17 Council
Study ID
NCT06942039
Phase
EARLY_PHASE1
Status
Recruiting
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Conditions

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

Eligibility Criteria

Sex
ALL
Age
N/A - 6 Years
Healthy Volunteers
Not accepted

Interventions

  • 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).
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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).
  • 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.
  • carboplatin — DRUG
    Consolidation: Intravenous Carboplatin given on days -3 \& -2 during consolidation alongside thiotepa and filgrastim.
  • Thiotepa — DRUG
    Consolidation: Intravenous Thiotepa given on days -3 \& -2 during consolidation alongside carboplatin and filgrastim.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.

Study Details

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.

Key Dates

Start date
Sep 23, 2025
Status verified
Jun 2026
Primary completion
Dec 31, 2030
Completion
Dec 31, 2032

Study Design

Enrollment
15 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Comprehensive Multimodal Therapy Including Induction, Consolidation, and Risk-Adapted Maintenance
    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.

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) ]

Central Contacts

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