Medulloblastoma
Conditions
Interventions
LDE225 oral suspension (50mg/mL) will be used for both adult and pediatric
patients and will be given on a daily basis for 4 weeks.
Sponsors
Novartis Pharma B.V.
Eligibility
Age
2 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients aged * 4 months Patients with histologically confirmed diagnosis of MB, who have experienced relapse or progression after standard-of-care therapy including radiotherapy or patients aged >4 months and * 6 years who are RT naive. Patients currently receiving steroids must have been on a stable (or decreasing) dose for at least 5 days before the brain/spine MRI obtained at screening. Patients with any number of prior relapses are eligible to enroll provided they have Hh-pathway activated tumors as assessed using the 5-gene Hh signature assay. Relapsed MB may be defined by imaging tumor biopsy, or evidence of tumor cells in the CSF. At least one measurable lesion.
Exclusion criteria
Exclusion criteria: Prior treatment with a Smoothened inhibitor Patients who have neuromuscular disorders that are associated with elevated CK Patients on concomitant treatment with drugs that are recognized to cause rhabdomyolysis that cannot be discontinued at least 2 weeks before first dose of study treatment. If it is essential that the patient stays on a statin to control hyperlipidemia only pravastatin may be used with extra caution. Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices that cannot be discontinued at least 2 weeks before first dose of study treatment and for the duration of the study. Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms, dose must have been stabilized (or decreasing) for at least 5 days before the brain/spine MRI obtained at screening. Patients receiving treatment with any enzyme-inducing anticonvulsant that cannot be discontinued at least 2 weeks before first dose of study treatment, and for the duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The overall response rate according to an independent review committee, defined as the proportion of patients with best overall response of complete response or partial response, as per tumor response guidelines and criteria for Medulloblastoma. | — |
Secondary
| Measure | Time frame |
|---|---|
| To investiagte the safety and efficacy of LDE225 with respect to ORR and PFS according to local investigator assessment To assess the efficacy of each treatment on duration of response (DoR) according to both ICR and local investigator assessment To assess the effect of each treatment on Overall survival (OS) To further characterize safety and tolerability of each treatment To further characterize the pharmacokinetics of LDE225 and any relevant metabolites | — |
Countries
Netherlands
Outcome results
None listed