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

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

Interventions

DRUG

Cytarabine IT

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).

DRUG

hydrocortisone

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

DRUG

Cisplatin

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).

DRUG

Vincristine

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).

DRUG

Etoposide

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.

DRUG

Cyclophosphamide

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.

DRUG

Mesna

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).

DRUG

Filgrastim

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.

DRUG

carboplatin

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

DRUG

Thiotepa

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

DRUG

Topotecan IT

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.

DRUG

Tamoxifen

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.

DRUG

ISOtretinoin

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.

DRUG

Celecoxib

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.

DRUG

etoposide phosphate

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.

DRUG

Temozolomide

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.

Sponsors & Collaborators

• C17 Council

  lead OTHER

Principal Investigators

• Sylvia Cheng · BC Cancer Centre

• Annie Huang · The Hospital for Sick Children

• Lucie Lafay-Cousin · Alberta Children's Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

6 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-23

Primary Completion

2030-12-31

Completion

2032-12-31

Countries

• Canada

Study Locations