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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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.


Detailed Summary:
Sponsor: Gustave Roussy, Cancer Campus, Grand Paris

Current Primary Outcome:

  • 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.
  • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Radiotherapy-free survival without event [ Time Frame: From inclusion up to 3 years ]
  • Overall Survival [ Time Frame: From inclusion up to 3 years ]


Original Secondary Outcome: Same as current

Information By: Gustave Roussy, Cancer Campus, Grand Paris

Dates:
Date Received: December 30, 2013
Date Started: September 2013
Date Completion: September 2022
Last Updated: June 8, 2016
Last Verified: June 2016