Study of Sequential High-dose Chemotherapy in Children With High Risk Medulloblastoma
Status:
Active, not recruiting
Trial end date:
2021-04-01
Target enrollment:
Participant gender:
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.