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

NCT ID: NCT01125800

Last Updated: 2017-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2014-10-31

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.

Conditions

Medulloblastoma; Rhabdomyosarcoma; Neuroblastoma; Hepatoblastoma; Glioma; Astrocytoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LDE225 233mg/m2 daily dose

Pediatric dose.

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

LDE225 372mg/m2 daily dose

Pediatric dose.

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

LDE225 425 mg/m2 daily dose

Pediatric dose.

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

LDE225 680 mg/m2 daily dose

Pediatric dose.

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

LDE225 800 mg/m2 daily dose

Adult dose

Group Type: EXPERIMENTAL

LDE225

Intervention Type: DRUG

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

Interventions

LDE225

LDE225/sonidegib capsules were supplied to the Investigators at dose strengths of 50 mg, 100 mg, 200 mg, and 250 mg.

Intervention Type: DRUG

Other Intervention Names

sonidegib

Eligibility 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

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Children's Healthcare of Atlanta Childern Hosp - ATL

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. John Hopkins

Baltimore, Maryland, United States

Dana Farber Cancer Institute DFCI (3)

Boston, Massachusetts, United States

Seattle Children's Hospital CPKC412A2114

Seattle, Washington, United States

Novartis Investigative Site

Parkville, Victoria, Australia

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Villejuif, , France

Novartis Investigative Site

Bologna, BO, Italy

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Roma, RM, Italy

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Novartis Investigative Site

Newcastle upon Tyne, , United Kingdom

Countries

United States; Australia; Canada; France; Italy; United Kingdom

Other Identifiers

2010-019348-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLDE225X2104

Identifier Type: -

Identifier Source: org_study_id