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Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma (HR MB-5)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02025881
Recruitment Status : Active, not recruiting
First Posted : January 1, 2014
Last Update Posted : February 25, 2021
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris

Brief Summary:

The trial includes i) the evaluation of the efficacy of a treatment strategy, designed as a phase II trial, and ii) a dose-finding part.

The Phase II trial is an open label, non-randomized, multicentre trial without control group. A Bayesian approach will be used to analyse the EFS, assuming a cure model. We will use three prior distributions of the EFS; (1) an enthusiastic prior distribution, (2) a pessimistic prior distribution, and (3) a non-informative prior distribution. As the patient outcomes in the trial will be recorded, the subsequent distribution of the outcome probability under experimental treatment will be computed by applying Bayes' theorem, which yields an estimated EFS probability with a 95% credibility interval (measure of Bayesian precision). Two interim analyses are planned to monitor the efficacy data (early stopping rules for futility or inefficacy).

The final analysis of efficacy will be made on an intention to treat basis, including all recruited patients, 3 years after recruitment of the last patient.

Due to the uncertainty on the dose of cyclophosphamide that can be given in combination with Busilvex for the last chemotherapy course in patients in complete response after intensification chemotherapy treatment, a dose-finding subtrial will be performed to address this issue (Phase I part). The dose escalation of cyclophosphamide will be performed using the Continual Reassessment Method in a Bayesian framework.

Condition or disease Intervention/treatment Phase
High-risk Medulloblastoma Drug: Carboplatin + etoposide Drug: Thiotepa Drug: Cyclophosphamide + Busilvex Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I / II Study of Sequential High-dose Chemotherapy With Stem Cell Support in Children Younger Than 5 Years of Age With High-risk Medulloblastoma
Actual Study Start Date : September 14, 2013
Actual Primary Completion Date : April 10, 2017
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Thiotepa

Arm Intervention/treatment
Experimental: Treatment
carboplatin + etoposide then thiotepa then Cyclophosphamide + Busilvex
Drug: Carboplatin + etoposide

Carboplatin 160 mg/m2 Day 1 to day 5 As an intravenous infusion over 1 hour. Dilution in 5 % glucose saline or sodium chloride 9 mg/ml (0.9%).

Etoposide 100 mg/m2 D ay 1 to day 5 As an intravenous infusion over 1 hour. Dilution in physiological saline or 5 % glucose saline while not exceeding a concentration of 0.4 mg/ml etoposide in the infusion bottle.

Drug: Thiotepa
Thiotepa 200 mg/m² Day-3 to day-1 As an intravenously infusion over 1 hour dilution in 200 ml/m² of 5% glucose saline or sodium chloride 9 mg/ml (0.9%)

Drug: Cyclophosphamide + Busilvex

Cyclophosphamide Level 1 20 mg/kg/day Level 2 30 mg/kg/day Level 3 40 mg/kg/day Level 4 50 mg/kg/day

Busilvex < 9 kgs 0.8 mg/kg/dose - 3.2 mg/kg/day 9 à < 16 kgs 0.96 mg/kg/dose - 3.84 mg/kg/day 16 à 23 kgs 0.88 mg/kg/dose - 3.52 mg/kg/day > 23 à 34 kgs 0.76 mg/kg/dose - 3.04 mg/kg/day > 34 kgs 0.64 mg/kg/dose

Primary Outcome Measures :
  1. Phase I - Maximum Tolerated Dose [ Time Frame: From inclusion to the Dose Limiting Toxicity up to 12 months ]
    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.

  2. Phase II - Event Free Survival [ Time Frame: From inclusion to Event up to 3 years ]
    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.

Secondary Outcome Measures :
  1. Radiotherapy-free survival without event [ Time Frame: From inclusion up to 3 years ]
  2. Overall Survival [ Time Frame: From inclusion up to 3 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 or other unfavourable histology confirmed by review and coordinating investigator
    • 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-Common Toxicity Criteria v4.0 grading system)
  • No prior irradiation or chemotherapy (except Vepesid - CBP)
  • Written informed consent from parents or legal guardian
  • All patients must be affiliated to a social security regimen or be a beneficiary of the same in order to be included in the study.

Inclusion criteria for the Phase I part of the study:

  • Complete response after intensification phase confirmed by central review
  • Adequate hepatic and renal function

Exclusion Criteria:

  • Desmoplastic medulloblastoma
  • Atypical Teratoid rhabdoid tumour
  • Uncontrolled active or symptomatic intracranial hypertension
  • Patient incapable of undergoing medical follow-up
  • Relapse of medulloblastoma

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02025881

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Gustave Roussy
Villejuif, Val De Marne, France, 94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
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Principal Investigator: Christelle Dufour, MD Gustave Roussy, Cancer Campus, Grand Paris
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Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT02025881    
Other Study ID Numbers: 2012-004842-14
2012/1908 ( Other Identifier: CSET number )
First Posted: January 1, 2014    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Additional relevant MeSH terms:
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Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors