Phase 2
N=59
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
Medulloblastoma · Rhabdomyosarcoma · Neuroblastoma · Hepatoblastoma · Glioma
Bottom Line
View on ClinicalTrials.gov: NCT01125800 ↗Enrolled (actual)
59
Serious AEs
47.4%
Results posted
Mar 2016
Primary outcome: Primary: Number of Participants With Dose-limiting Toxicities (DLT) in Phase I — 0; 1; 0; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- LDE225 (Drug)
- Age
- Pediatric, Adult · 0+ yrs
- Sex
- All
- Sponsor
- Novartis Pharmaceuticals
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLT) in Phase I |
0; 1; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Sonidegib for Prolonged Use |
680 | — |
| PRIMARY Percentage of Participants With Objective Response Rate (ORR) by Treatment |
3.3; 12.5; 0; 6.3; 8.3; 37.5 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs and Death During the Study |
11; 16; 11; 22; 16; 8 | — |
| SECONDARY Area Under the Drug Concentration Time Curve From Time Zero to 24 Hours After Dosing (AUC0-24h) of Sonidegib in Phase I |
1981.56; 2194.29; 5309.44; 5117.61; 10589.53; 15431.43 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of Sonidegib in Phase I |
3.98; 2.03; 2.92; 2.08; 1.98; 2.06 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Sonidegib in Phase I |
191.18; 246.39; 642.5; 618.88; 769.22; 944.17 | — |
| SECONDARY Percentage of Pediatric Participants With Objective Response Rate (ORR) by Hedgehog (Hh) Signaling Pathway Status |
66.7 | — |
| SECONDARY Duration of Response by Treatment |
7; 8.1; 4.86 | — |
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.
Eligibility Criteria
Inclusion Criteria
- Phase I - Patients aged ≥12 months and 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
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
Data sourced from ClinicalTrials.gov (NCT01125800). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.