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

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: May 12, 2010
Last updated: March 25, 2015
Last verified: March 2015

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.

Condition Intervention Phase
High Grade Glioma,
Drug: LDE225
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Phase I - Determine the maximum tolerated dose of and characterize the dose limiting toxicities of LDE225. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Phase II - Assess preliminary efficacy of LDE225, as determined by objective response rate [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Characterize the safety and tolerability of LDE225 treatment [ Time Frame: 28 day cycles ] [ Designated as safety issue: Yes ]
  • Characterize the pharmacokinetics of LDE225 [ Time Frame: 28 day cycles ] [ Designated as safety issue: No ]
  • Determine tumor response [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
  • Assess the Hh gene expression signature and the mutational status of Hh pathway genes [ Time Frame: once ] [ Designated as safety issue: No ]

Enrollment: 76
Study Start Date: February 2011
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDE225 Drug: LDE225


Ages Eligible for Study:   12 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01125800

United States, Georgia
Children's Healthcare of Atlanta Childern Hosp - ATL
Atlanta, Georgia, United States, 30342
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. John Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Dana Farber Cancer Institute DFCI (3)
Boston, Massachusetts, United States, 02115
United States, Washington
Seattle Children's Hospital CPKC412A2114
Seattle, Washington, United States, 98105
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3052
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1X8
Novartis Investigative Site
Paris, France, 75231
Novartis Investigative Site
Villejuif Cedex, France, 94805
Novartis Investigative Site
Bologna, BO, Italy, 40139
Novartis Investigative Site
Milano, MI, Italy, 20133
Novartis Investigative Site
Roma, RM, Italy, 00168
United Kingdom
Novartis Investigative Site
Sutton, Surrey, United Kingdom, SM2 5PT
Novartis Investigative Site
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01125800     History of Changes
Other Study ID Numbers: CLDE225X2104  2010-019348-37 
Study First Received: May 12, 2010
Last Updated: March 25, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Australia: Department of Health and Ageing Therapeutic Goods Administration
Italy: Ministry of Health
Spain: Spanish Agency of Meicines
Canada: Health Canada

Keywords provided by Novartis:
hedgehog pathway inhibitor, adult

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Muscle Tissue
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral

ClinicalTrials.gov processed this record on February 04, 2016