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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	N/A - 5 Years
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02025881
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Gustave Roussy, Cancer Campus, Grand Paris
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Christelle Dufour, MD
Principal Investigator Affiliation	Gustave Roussy, Cancer Campus, Grand Paris
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	France
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	High-risk Medulloblastoma

Arms & Interventions

Arms

Experimental: Treatment

carboplatin + etoposide then thiotepa then Cyclophosphamide + Busilvex

Interventions

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

Contact a Trial Team

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