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

Phase 1

• Conditions: Phase I part: pediatric patients with recurrent or refractory medulloblastoma or other tumors potentially dependent on the Hedgehog-signaling pathway (rhabdomyosarcoma, neuroblastoma, hepatoblastoma, high-grade glioma, or osteosarcoma) Phase II part: pediatric and adult patients with recurrent or refractory medulloblastoma; MedDRA version: 14.1 Level: PT Classification code 10039027 Term: Rhabdomyosarcoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1 Level: PT Classification code 10031296 Term: Osteosarcoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1 Level: PT Classification code 10019823 Term: Hepatoblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1 Level: PT Classification code 10065443 Term: Malignant glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1 Level: PT Classification code 10066595 Term: Neuroblastoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1 Level: PT Classification code 10066594 Term: Medulloblastoma recurrent System Organ Class: 10029104 - N; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-019348-37-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-11-29
• Study Completion: 2014-10-03
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 76

Inclusion Criteria

Phase I:
- Patients aged = 12 months and < 18 years
- Histologically confirmed diagnosis of MB, 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 from this study)
- Adequate renal function
- Adequate liver function
- Adequate bone marrow function
- Women of child-bearing potential must be using two forms of highly effective methods of contraception throughout the study and for 6 months after the last study treatment.
- Sexually active males must use a condom during intercourse while taking LDE225 and for 6 months after stopping LDE225 treatment

Phase II:
- Patients aged = 12 months
- Histologically confirmed diagnosis of recurrent or refractory MB,
- At least one measureable lesion
- Adequate renal function
- Adequate liver function
- Adequate bone marrow function
- Women of child-bearing potential must be using two forms of highly effective methods of contraception throughout the study and for 6 months after the last study treatment.
- Sexually active males must use a condom during intercourse while taking LDE225 and for 6 months after stopping LDE225 treatment

Other protocol defined inclusion criteria may apply.

Are the trial subjects under 18? yes
Number of subjects for this age range: 85
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

- Systemic anticancer treatment within 2 weeks before first dose of study
- Focal radiation therapy within 4 weeks before first dose of study treatment, or full spinal radiotherapy within 3 months of first dose of study treatment.
- Investigational agents within 2 weeks or = 5 x t1/2 (whichever is longer) before start of study therapy.
- Unresolved toxicity greater than CTCAE grade 1 from previous anticancer therapy or radiation therapy, or incomplete recovery from previous surgeryPatients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9,
- Patients receiving unstable or increasing doses of corticosteroids.
- Patients receiving treatment with any enzyme-inducing anticonvulsant
- 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 who require a nasogastric tube for drug administration
- Any concurrent severe and/or uncontrolled medical conditions that in the investigator’s opinion could put the patient at greater risk for treatment-related toxicities or confound the interpretation of clinical outcomes.
- Patients who have neuromuscular disorders that are associated with elevated CK
- Impaired cardiac function or clinically significant heart disease,
- Pregnant or nursing (lactating) females.
- Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C
- Impairment of GI function or GI disease
- Patients on concomitant treatment with drugs that are recognized to cause rhabdomyolysis,
- Patients who are planning on embarking on a new strenuous exercise regimen after initiation of study treatment.

Other protocol defined exclusion criteria may apply.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified