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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01125800




Registration number
NCT01125800
Ethics application status
Date submitted
12/05/2010
Date registered
18/05/2010
Date last updated
20/03/2017

Titles & IDs
Public title
A Phase I Dose Finding and Safety Study of Oral LDE225 in Children and a Phase II Portion to Assess Preliminary Efficacy in Recurrent or Refractory MB
Scientific title
A Phase I/II Study of LDE225 in Pediatric Patients With Recurrent or Refractory Medulloblastoma or Other Tumors Potentially Dependent on the Hedgehog-signaling Pathway and Adult Patients With Recurrent or Refractory Medulloblastoma
Secondary ID [1] 0 0
2010-019348-37
Secondary ID [2] 0 0
CLDE225X2104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Rhabdomyosarcoma 0 0
Neuroblastoma 0 0
Hepatoblastoma 0 0
Glioma 0 0
Astrocytoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LDE225

Experimental: LDE225 233mg/m2 daily dose - Pediatric dose.

Experimental: LDE225 372mg/m2 daily dose - Pediatric dose.

Experimental: LDE225 425 mg/m2 daily dose - Pediatric dose.

Experimental: LDE225 680 mg/m2 daily dose - Pediatric dose.

Experimental: LDE225 800 mg/m2 daily dose - Adult dose


Treatment: Drugs: LDE225
LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-limiting Toxicities (DLT) in Phase I
Timepoint [1] 0 0
Baseline, End of dose escalation part (Day 42)
Primary outcome [2] 0 0
Maximum Tolerated Dose (MTD) of Sonidegib for Prolonged Use
Timepoint [2] 0 0
Baseline, End of dose escalation part (Day 42)
Primary outcome [3] 0 0
Percentage of Participants With Objective Response Rate (ORR) by Treatment
Timepoint [3] 0 0
Baseline, Day 28 of Cycle 2, End of treatment (Within 14 days of last dose)
Secondary outcome [1] 0 0
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs and Death During the Study
Timepoint [1] 0 0
Baseline (start of study treatment) up to End of treatment (Within 14 days of last dose)
Secondary outcome [2] 0 0
Area Under the Drug Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC0-24h) of Sonidegib in Phase I
Timepoint [2] 0 0
Pre-dose, 0.5, 1, 2, 4, 7 hours (± 15 min) post-dose at Day 1 and Day 22 of Cycle 1
Secondary outcome [3] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sonidegib in Phase I
Timepoint [3] 0 0
Pre-dose, 0.5, 1, 2, 4, 7 hours (± 15 min) post-dose at Day 1 and Day 22 of Cycle 1
Secondary outcome [4] 0 0
Maximum Observed Plasma Concentration (Cmax) of Sonidegib in Phase I
Timepoint [4] 0 0
Pre-dose, 0.5, 1, 2, 4, 7 hours (± 15 min) post-dose at Day 1 and Day 22 of Cycle 1
Secondary outcome [5] 0 0
Percentage of Pediatric Participants With Objective Response Rate (ORR) by Hedgehog (Hh) Signaling Pathway Status
Timepoint [5] 0 0
Baseline, Day 28 of Cycle 2, End of treatment (Within 14 days of last dose)
Secondary outcome [6] 0 0
Duration of Response by Treatment
Timepoint [6] 0 0
Baseline, Day 28 of Cycle 2, End of treatment (Within 14 days of last dose)

Eligibility
Key inclusion criteria
* Phase I - Patients aged =12 months and <18 years, Phase II - Patients =12 months
* Phase I - Histologically confirmed diagnosis of medulloblastoma, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, high grade glioma, or osteosarcoma, that has progressed despite treatment with standard therapies, or for which no standard treatments are available (patients with brainstem gliomas are excluded). Phase II - Histologically confirmed diagnosis of recurrent or relapsed medulloblastoma with at least one measurable lesion.
* Performance Status: Karnofsky =60% for patients >10 yrs, Lansky =50 for patients less than or equal to 10 yrs
* Protocol-defined renal , liver and bone marrow function
* Negative pregnancy test before starting study treatment. If of child bearing potential must use 'highly effective' methods of contraception.
* All patients must consent to provide a tumor sample
Minimum age
12 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Systemic anti-cancer treatment within 2 weeks prior to first dose (6 weeks for nitrosourea, mitomycin and monoclonal antibodies).
* Focal radiotherapy within 4 weeks prior to first dose, or full spinal radiotherapy within 3 months of first dose.
* Unresolved toxicity greater than CTCAE grade 1 from previous anti-cancer therapy or radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia or other specifications in the eligibility criteria for this study), or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal Investigator (PI) and documented.
* Major surgery, serious illness or traumatic injury within 2 weeks of starting study therapy. Patients anticipated to require major surgery within the first 2 cycles of treatment.
* Patients requiring a nasogastric tube for drug administration (G-tubes are permitted)
* Impaired cardiac function
* Pregnant or breast-feeding females
* Impairment of gastrointestinal (GI) function or GI disease

Other protocol-defined inclusion/exclusion criteria may apply

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 1
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
1/02/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
76
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
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
Washington
Country [5] 0 0
Canada
State/province [5] 0 0
Ontario
Country [6] 0 0
France
State/province [6] 0 0
Paris
Country [7] 0 0
France
State/province [7] 0 0
Villejuif Cedex
Country [8] 0 0
Italy
State/province [8] 0 0
BO
Country [9] 0 0
Italy
State/province [9] 0 0
MI
Country [10] 0 0
Italy
State/province [10] 0 0
RM
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Surrey
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Newcastle Upon Tyne

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

Ethics approval
Ethics application status

Summary
Brief summary
Phase I dose-escalation study to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of LDE225 given orally on a daily dosing schedule in children with recurrent or refractory medulloblastoma, or other tumors potentially dependent on Hedgehog signaling pathway.

Phase II study is to assess preliminary efficacy in both adult and pediatric patients with recurrent or refractory MB.
Trial website
https://clinicaltrials.gov/study/NCT01125800
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01125800