A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: October 11, 2012
Last updated: October 7, 2016
Last verified: October 2016
This Phase II study evaluates the safety and efficacy of LDE225 in adult and pediatric patients with Hh-pathway activated, relapsed MB.
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Overall response rate (ORR) [ Time Frame: 8 weeks ]
ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR). (As per Tumor response guidelines and criteria for Medulloblastoma.
ORR will be done by independent central review.
Secondary Outcome Measures:
- Progression free survival (PFS) [ Time Frame: 8 weeks ]
PFS is defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause
- Overall response rate (ORR) [ Time Frame: 8 weeks ]
As per Tumor response guidelines and criteria for Medulloblastoma. ORR will be done by local investigator assessment.
- Duration of response (DoR) [ Time Frame: 8 weeks ]
DoR is defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma.
- Overall survival (OS) [ Time Frame: 4 weeks ]
OS is defined as the time from date of randomization to date of death due to any cause.
- Safety and tolerability of LDE225 treatment [ Time Frame: 4 weeks ]
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 (e.g., panorex or age appropriate dental x-ray), and dental exams (as appropriate for age)
- Pharmacokinetics (Pk) - Cmin [ Time Frame: 2 weeks ]
PK of LDE225 and any relevant metabolites
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||October 2016 (Final data collection date for primary outcome measure)
Experimental: relapsed after standard of care therapy
Relapsed after standard-of-care therapy including RT or children ≤ to 6 years who are RT-naive
|Ages Eligible for Study:
||4 Months and older (Child, Adult, Senior)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
- 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:
- Karnofsky performance status score ≥ 50 for patients >16 years of age
- Lansky performance status score ≥ 50 for patients ≤ 16 years of age
Adequate bone marrow function as defined as:
- Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 80 x 109/L
- Hemoglobin (Hgb) ≥ 9 g/dL
- Serum CK ≤1.5 ULN
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01708174
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 11, 2012
||October 7, 2016
Keywords provided by Novartis:
Hh pathway inhibitor,
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 22, 2017
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue