High-risk medulloblastoma MedDRA version: 16.0 Level: PT Classification code 10027107 Term: Medulloblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Endoxan
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
CAS Number: 50-18-0
Concentration unit: mg milligram(s)
Sponsors
Institut de cancérologie Gustave Roussy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histological diagnosis of medulloblastoma with no INI-1 loss - High risk medulloblastoma defined by at least one of the following conditions: Newly diagnosed classical metastatic medulloblastoma Newly diagnosed anaplastic/large cell medulloblastoma Newly diagnosed medulloblastoma with amplification of c-myc or N-myc - Age at initial biopsy less or equal than 5 years - Weight compatible with leukapheresis - Ability to comply with requirements for submission of materials for central review - Nutritional and general status compatible with this therapy, Lansky play score = 30% - Estimated life expectancy =3 months - No organ toxicity other than neurological symptoms (grade >2 according to NCI-CTC v4.0 grading system) - No prior irradiation or chemotherapy (except VP16 – CBP) - Written informed consent from parents or legal guardian Inclusion criteria for the Phase I part of the study: - Complete response after intensification phase confirmed by central review - Adequate hepatic and renal function Are the trial subjects under 18? yes Number of subjects for this age range: 50 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Desmoplastic medulloblastoma - Atypical Teratoid rhabdoid tumour - Uncontrolled active or symptomatic intracranial hypertension - Patient incapable of undergoing medical follow-up - Relapse of medulloblastoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase II: To assess the efficacy in terms of Event Free Survival (EFS) of the strategy intended to treat children younger than 5 years of age suffering from high-risk medulloblastoma with sequential high-dose chemotherapy without radiotherapy. Phase I: To determine the Maximum Tolerated Dose (MTD) of cyclophosphamide in combination with a fixed dose of Busilvex in children with high-risk medulloblastoma who are in complete response after the intensification phase. ;Secondary Objective: To assess feasibility and efficacy of a strategy without radiotherapy by estimating the rate of patients alive free of disease without having received radiation therapy To assess efficacy of this strategy in terms of Overall Survival To assess the proportion of radiological tumour response of VP16-Carboplatin courses To assess the proportion of patients achieving complete response after 2 courses of VP16-carboplatine followed by 2 courses of thiotepa To characterize the pharmacokinetics of cyclophosphamide – Busilvex combination (Phase I) To assess efficacy, feasibility and tolerance of salvage treatment To evaluate the acute toxicity of this therapeutic strategy, overall and by treatment phase (induction / intensification / consolidation) To evaluate the prognostic value of some immunohistochemical markers on the risk of relapse or progression To evaluate neurocognitive development of patients within 10 years after the end of treatment ;Primary end point(s): For the whole study : Event Free Survival For the Phase I part of the study : Dose Limiting Toxicity | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Radiotherapy-free survival without event ; - Overall survival ; - Response (complete and partial response) to conventional chemotherapy assessed after the first two courses ; - Complete response to induction and intensification phases assessed after the two courses of thiotepa ; - Toxicity according to NCI-CTC v4.0 grading system, in particular after the course of cyclophosphamide in combination with Busilvex to estimate the maximum tolerated dose of cyclophosphamide in this setting (phase I part) ; - Pharmacokinetics of cyclophosphamide and Busilvex ; - Response to salvage treatment ; - Cognitive assessments ; | — |
Countries
France
Outcome results
None listed