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: 19.1Level: 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-SE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
- 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: 2
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
- Prior treatment with a Smoothened inhibitor
- 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:<br>- ORR according to local investigator assessment<br>- Progression free survival (PFS) according to both ICR and local investigator assessment<br>- Duration of response (DoR) according to both ICR and local investigator assessment<br>- Overall survival (OS)<br><br>To further characterize the safety and tolerability of LDE225 treatment <br><br>To further characterize the pharmacokinetics of LDE225 and any relevant metabolites<br>;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)<br>- DoR (duration of response)<br>- OS (overall survival)<br>- 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)<br>- PK (Cmin)<br>;Timepoint(s) of evaluation of this end point: As defined in table 7-1 of the protocol.<br>Adverse events: continuously.<br>