A Phase II, multi-center, open-label, single-arm study of the efficacy and safety of oral LDE225 in patients with Hh-pathway activated relapsed medulloblastoma
- Conditions
- Medulloblastomamalignant brain tumor10029211
- Registration Number
- NL-OMON39614
- Lead Sponsor
- ovartis Pharma B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The overall response rate according to an independent review committee, defined<br /><br>as the proportion of patients with best overall response of complete response<br /><br>or partial response, as per tumor response guidelines and criteria for<br /><br>Medulloblastoma.</p><br>
- Secondary Outcome Measures
Name Time Method <p>To investiagte the safety and efficacy of LDE225 with respect to ORR and PFS<br /><br>according to local investigator assessment<br /><br>To assess the efficacy of each treatment on duration of response (DoR)<br /><br>according to both ICR and local investigator assessment<br /><br>To assess the effect of each treatment on Overall survival (OS)<br /><br>To further characterize safety and tolerability of each treatment<br /><br>To further characterize the pharmacokinetics of LDE225 and any relevant<br /><br>metabolites </p><br>