Clinical Trials /

Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma

NCT02025881

Description:

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.

Related Conditions:
  • Medulloblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2012-004842-14
  • SECONDARY ID: 2012/1908
  • NCT ID: NCT02025881

Conditions

  • High-risk Medulloblastoma

Interventions

DrugSynonymsArms
Carboplatin + etoposideTreatment
ThiotepaTreatment
Cyclophosphamide + BusilvexTreatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalcarboplatin + etoposide then thiotepa then Cyclophosphamide + Busilvex
  • Carboplatin + etoposide
  • Thiotepa
  • Cyclophosphamide + Busilvex

Eligibility 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 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
      
Maximum Eligible Age:5 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I - Maximum Tolerated Dose
Time Frame:From inclusion to the Dose Limiting Toxicity up to 12 months
Safety Issue:
Description: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 Outcome Measures

Measure:Radiotherapy-free survival without event
Time Frame:From inclusion up to 3 years
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:From inclusion up to 3 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gustave Roussy, Cancer Campus, Grand Paris

Last Updated