A clinical study to test the efficacy and safety of LDE225 compared to temozolomide in patients with a specific type of brain tumour
- Conditions
- Relapsed medulloblastoma characterised by Hedgehog (Hh)-pathway activationMedDRA version: 14.1Level: PTClassification code 10066594Term: Medulloblastoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-003066-40-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 109
- Patients aged >= 4 months - Patients with histologically confirmed diagnosis of MB, who have experienced relapse or progression - Only patients with a test result, using the 5-gene Hh signature assay, indicating Hh-pathway activated MB are eligible for this study. - At least one measurable lesion - Adequate renal function - Adequate liver function - Adequate bone marrow function - Serum CK <= 1.5 ULN Other protocol defined inclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
- Systemic anticancer treatment within 2 weeks before first dose of study treatment - Focal radiation therapy within 4 weeks before first dose of study treatment, or full spinal radiotherapy within 3 months before first dose of study treatment. - Patients who have neuromuscular disorders that are associated with elevated CK - Any concurrent severe and/or uncontrolled medical conditions that in the investigator's opinion could put the patient at greater risk for treatment-related toxicities or confound the interpretation of clinical outcomes. - Impaired cardiac function - Clinically significant heart disease - Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C - Impairment of GI function or GI disease - Major surgery, serious illness, or traumatic injury within 2 weeks of first dose of study treatment. - Unresolved toxicity greater than CTCAE grade 1 from previous anticancer therapy - Patients anticipated to require major surgery within the first 8 weeks of treatment - Patients who require a nasogastric tube for drug administration - Patients on concomitant treatment with drugs that are recognized to cause rhabdomyolysis - Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9. - Patients receiving unstable or increasing doses of corticosteroids - 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 - Investigational agents within 4 weeks or = 5 x t1/2 (whichever is longer) before first dose of study treatment. - Pregnant females. - Patients who are not willing to apply highly effective contraception. - Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. Other protocol defined exclusion criteria may apply.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess efficacy of LDE225 with respect to the Overall Response Rate (ORR) according to independent central review (ICR);Secondary Objective: To assess the efficacy of LDE225 with respect to: - ORR according to local investigator assessment - Progression free survival (PFS) according to both ICR and local investigator assessment - Duration of response (DoR) according to both ICR and local investigator assessment - Overall survival (OS) To further characterize the safety and tolerability of LDE225 treatment To further characterize the pharmacokinetics of LDE225 and any relevant metabolites;Primary end point(s): ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR).;Timepoint(s) of evaluation of this end point: every 8 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - PFS (progression free survival) - DoR (duration of response) - OS (overall survival) - Adverse and serious adverse events, clinically significant changes in hematology and chemistry values, assessment of physical and/or neurological examinations, vital signs, electrocardiograms, bone x-rays, dental x-rays, and dental exams (as appropriate for age) - PK (Cmin);Timepoint(s) of evaluation of this end point: Efficacy endpoint: Every 8 weeks. Adverse events: continuously. PK: every other week during the first 8 weeks of treatment