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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02025881|
Recruitment Status : Recruiting
First Posted : January 1, 2014
Last Update Posted : June 9, 2016
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||September 2013|
|Estimated Primary Completion Date :||September 2018|
|Estimated Study Completion Date :||September 2022|
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.
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
- 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.
- Radiotherapy-free survival without event [ Time Frame: From inclusion up to 3 years ]
- Overall Survival [ Time Frame: From inclusion up to 3 years ]
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
|Contact: Dufour Christelle, MD||0142114247 ext +firstname.lastname@example.org|
|Contact: Perrine Capolino||0142113590 ext +email@example.com|
|Villejuif, Val de Marne, France, 94805|
|Contact: Christelle Dufour, MD 0142114247 ext +33 firstname.lastname@example.org|
|Contact: Perrine Capolino 0142113590 ext +33 email@example.com|
|Principal Investigator: Christelle Dufour, MD|
|Principal Investigator:||Christelle Dufour, MD||Gustave Roussy, Cancer Campus, Grand Paris|