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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01708174
Registration number
NCT01708174
Ethics application status
Date submitted
11/10/2012
Date registered
16/10/2012
Date last updated
11/08/2017
Titles & IDs
Public title
A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
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Scientific title
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
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Secondary ID [1]
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CLDE225C2301
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma
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Condition category
Condition code
Cancer
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Children's - Brain
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Cancer
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Brain
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LDE225
Treatment: Drugs - TMZ
Experimental: Sonidegib (LDE225) - 600 mg orally for adults and 500 mg/m2 orally for children
Active comparator: Temozolamide (TMZ) - 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study.
Treatment: Drugs: LDE225
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.
Treatment: Drugs: TMZ
Temozolomide capsules were obtained locally by the Investigator
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [1]
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ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants.
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Timepoint [1]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [1]
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Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [1]
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PFS was 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 (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). TMZ participants without event prior to crossover were censored.
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Timepoint [1]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [2]
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PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [2]
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PFS was 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. PFS was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma.
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Timepoint [2]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [3]
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Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [3]
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ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). ORR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. Assessments after crossover were not included for TMZ patients.
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Timepoint [3]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [4]
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Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [4]
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DoR was 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. DoR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. TMZ participants without an event prior to crossover were censored.
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Timepoint [4]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [5]
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Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
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Assessment method [5]
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OS was defined as the time from date of randomization to date of death due to any cause. All deaths are considered, including deaths occurred after crossover for TMZ participants.
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Timepoint [5]
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from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
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Secondary outcome [6]
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Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225)
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Assessment method [6]
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Blood samples were collected for assessment. The children's group was analyzed up until week 25 only.
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Timepoint [6]
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Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53
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Eligibility
Key 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
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Minimum age
4
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
6/05/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
5/10/2016
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Sample size
Target
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Accrual to date
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Final
22
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Recruitment in Australia
Recruitment state(s)
QLD,WA
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Recruitment hospital [1]
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Novartis Investigative Site - Herston
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Recruitment hospital [2]
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Novartis Investigative Site - Perth
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Recruitment postcode(s) [1]
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4029 - Herston
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Recruitment postcode(s) [2]
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6840 - Perth
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Recruitment outside Australia
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United States of America
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Illinois
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United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Pennsylvania
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United States of America
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Texas
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United States of America
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Washington
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Brazil
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SP
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Canada
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Ontario
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France
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Aquitaine
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France
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Angers Cedex 1
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France
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Lille Cedex
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France
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Paris
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France
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Toulouse Cedex 9
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France
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Vandoeuvre les Nancy
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France
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Villejuif Cedex
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Germany
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Augsburg
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Germany
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Essen
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Germany
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Hamburg
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Italy
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BO
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Italy
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MI
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Italy
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RM
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Italy
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TO
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Netherlands
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Rotterdam
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Russian Federation
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Russia
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Spain
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Andalucia
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Madrid
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Sweden
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Goteborg
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Switzerland
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Zürich
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United Kingdom
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Surrey
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United Kingdom
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Leeds
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This Phase II study evaluated the safety and efficacy of LDE225 in adult and pediatric patients with Hh-pathway activated, relapsed MB.
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Trial website
https://clinicaltrials.gov/study/NCT01708174
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Contact person for public queries
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01708174
Download to PDF