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

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Glioma; Neuroblastoma; Astrocytoma; Rhabdomyosarcoma; Medulloblastoma; Hepatoblastoma

Treatments: Drug: LDE225

Study type: Interventional

Funder types: Industry

Identifiers

NCT01125800

CLDE225X2104

2010-019348-37 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 76 patients

Sex: All

Ages: 12 months to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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76 participants in 5 patient groups

LDE225 233mg/m2 daily dose

Experimental group

Description:

Pediatric dose.

Treatment:

Drug: LDE225

LDE225 372mg/m2 daily dose

Experimental group

Description:

Pediatric dose.

Treatment:

Drug: LDE225

LDE225 425 mg/m2 daily dose

Experimental group

Description:

Pediatric dose.

Treatment:

Drug: LDE225

LDE225 680 mg/m2 daily dose

Experimental group

Description:

Pediatric dose.

Treatment:

Drug: LDE225

LDE225 800 mg/m2 daily dose

Experimental group

Description:

Adult dose

Treatment:

Drug: LDE225