A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
Condition: Medulloblastoma
MeSH terms: Medulloblastoma
Intervention: LDE225; TMZ
Intervention description: Sonidegib for oral suspension was supplied in amber glass bottles. Sonidegib oral suspension was combined with the supplied reconstitution vehicle to a final concentration of 50 mg/mL.; Temozolomide capsules were obtained locally by the Investigator
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 4 Months
Healthy volunteers: No
Keywords: medulloblastoma,; relapsed,; pediatric,; children,; adults,; Hh pathway inhibitor,; LDE225

Summary:

      This Phase II study evaluated the safety and efficacy of LDE225 in adult and pediatric
      patients with Hh-pathway activated, relapsed MB.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically confirmed diagnosis of MB, who have experienced relapse
             or progression after standard-of-care therapy including radiotherapy. Patients
             currently receiving steroids must have been on a stable (or decreasing) dose for at
             least 5 days before initiating study therapy.

          -  Only patients with a test result, using the 5-gene Hh signature assay, indicating
             Hhpathway activated MB are eligible for this study. All available tumor material
             obtained at any time during the course of the patient's disease should be submitted
             for these analyses

          -  At least one measurable lesion defined as lesion(s) that can be accurately measured in
             at least two dimensions and is ≥ 10 mm in each dimension by Gadolinium (Gd)-MRI,
             irrespective of slice thickness/reconstruction interval, for CNS lesions and CT or MRI
             (with or without contrast) for non-CNS lesions. All patients with CNS lesions must
             have a brain MRI with and without gadolinium and a spine MRI with gadolinium within 2
             weeks prior to first dose of study treatment.

          -  Performance Status corresponding to ECOG score of 0, 1, or 2:

               1. Karnofsky performance status score ≥ 50 for patients >16 years of age

               2. Lansky performance status score ≥ 50 for patients ≤ 16 years of age

          -  Adequate bone marrow function as defined as:

               1. Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               2. Platelet count ≥ 80 x 109/L

               3. Hemoglobin (Hgb) ≥ 9 g/dL

          -  Serum CK ≤1.5 ULN

        Exclusion Criteria:

          -  Prior treatment with a Smoothened inhibitor Systemic anticancer treatment within 2
             weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and
             monoclonal antibodies).

          -  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 (eg,
             inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
             muscular atrophy).

          -  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 first dose of study
             treatment.