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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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)
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
Secondary ID [1] 0 0
CLDE225C2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [1] 0 0
Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
Timepoint [1] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [2] 0 0
PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
Timepoint [2] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [5] 0 0
Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016
Timepoint [5] 0 0
from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225)
Timepoint [6] 0 0
Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53

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
Minimum age
4 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/10/2016
Sample size
Target
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [2] 0 0
Novartis Investigative Site - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
6840 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Brazil
State/province [9] 0 0
SP
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
France
State/province [11] 0 0
Aquitaine
Country [12] 0 0
France
State/province [12] 0 0
Angers Cedex 1
Country [13] 0 0
France
State/province [13] 0 0
Lille Cedex
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
France
State/province [15] 0 0
Toulouse Cedex 9
Country [16] 0 0
France
State/province [16] 0 0
Vandoeuvre les Nancy
Country [17] 0 0
France
State/province [17] 0 0
Villejuif Cedex
Country [18] 0 0
Germany
State/province [18] 0 0
Augsburg
Country [19] 0 0
Germany
State/province [19] 0 0
Essen
Country [20] 0 0
Germany
State/province [20] 0 0
Hamburg
Country [21] 0 0
Italy
State/province [21] 0 0
BO
Country [22] 0 0
Italy
State/province [22] 0 0
MI
Country [23] 0 0
Italy
State/province [23] 0 0
RM
Country [24] 0 0
Italy
State/province [24] 0 0
TO
Country [25] 0 0
Netherlands
State/province [25] 0 0
Rotterdam
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Russia
Country [27] 0 0
Spain
State/province [27] 0 0
Andalucia
Country [28] 0 0
Spain
State/province [28] 0 0
Catalunya
Country [29] 0 0
Spain
State/province [29] 0 0
Comunidad Valenciana
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Sweden
State/province [31] 0 0
Goteborg
Country [32] 0 0
Switzerland
State/province [32] 0 0
Zürich
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Surrey
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Leeds

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01708174
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries