Trial record 2 of 12 for:    Open Studies | "Hepatoblastoma"

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 is currently recruiting participants.
Verified March 2013 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01125800
First received: May 12, 2010
Last updated: March 7, 2013
Last verified: March 2013
  Purpose

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
Medulloblastoma,
Rhabdomyosarcoma,
Neuroblastoma,
Hepatoblastoma,
High Grade Glioma,
Astrocytoma
Drug: LDE225
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Parallel 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 ]

Estimated Enrollment: 91
Study Start Date: February 2011
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LDE225 Drug: LDE225

  Eligibility

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

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

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 21 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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 7, 2013
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:
Recurrent,
refractory,
medulloblastoma,
rhabdomyosarcoma,
neuroblastoma,
hepatoblastoma,
astrocytoma,
children,
pediatric,
hedgehog pathway inhibitor, adult

Additional relevant MeSH terms:
Hepatoblastoma
Astrocytoma
Glioma
Medulloblastoma
Neuroblastoma
Rhabdomyosarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on May 22, 2013