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
The purpose of this study is to find the 1) highest dose of the investigational drug LDE225 that can be given safely to children with medulloblastoma, rhabdomyosarcoma, neuroblastoma, hepatoblastoma, high grade glioma, or osteosarcoma and 2) best dose of LDE225 for use in future studies with children. The study results may also provide a better understanding of how well the drug works in children.
Inclusion criteria ï¿½ Patients aged less than / equal to 12 months and less than 18 years ï¿½ 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 from this study). ï¿½ Adequate Performance Status ï¿½ Adequate kidney, liver, and bone marrow function ï¿½ A negative pregnancy test for females, and use of highly effective contraception for males and females ï¿½ Written informed consent/assent before any study-specific procedures ï¿½ All patients must consent to provide a tumor sample (archival or fresh). The tumor material submitted for these analyses may have been obtained at any time during the course of the patient's disease. Exclusion criteria: ï¿½ Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies). ï¿½ 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. ï¿½ Investigational agents within 2 weeks or less than / equal to 5x t1/2 (whichever is longer) before starting study drug. ï¿½ Unresolved toxicity or incomplete recovery from previous surgery, unless agreed by Novartis and the Principal nvestigator (PI) and documented. ï¿½ Patients receiving treatment with certain medications that are known to interact with LDE225 that cannot be discontinued at least 1 week before start of study therapy, and for the duration of the study. ï¿½ Patients receiving unstable or increasing doses of corticosteroids. ï¿½ Patients receiving treatment with enzyme-inducing anticonvulsants that cannot be discontinued at least 1 week before start of study therapy, and for the duration of the study. Patients on non-enzyme-inducing anticonvulsants are eligible. ï¿½ Major surgery, serious illness, or traumatic injury within 2 weeks of starting study therapy. ï¿½ Patients anticipated to require major surgery during the first 2 cycles of treatment in this study. ï¿½ Patients who require a nasogastric tube for drug administration (G-tubes are permitted) ï¿½ Any concurrent severe and/or uncontrolled medical conditions hat in the investigator's opinion could put the patient at greater risk for treatment-related toxicities or confound the interpretation of clinical outcomes. ï¿½ Patients who have neuromuscular disorders that are associated with elevated CPK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). ï¿½ Impaired cardiac function or clinically significant heart disease ï¿½ Pregnant or breast-feeding females. ï¿½ Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C (testing is not mandatory for study entry). ï¿½ Impairment of GI function or GI disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) ï¿½ Patients who in the investigator's opinion may be unwilling, unable, or unlikely to comply with the requirements of the study protocol.
The dose-escalation part of the study has been completed. The highest safest dose has been determined. Once the highest dose that can be safely given to children is identified in the dose-escalation part, more patients will join the study; all patients in the safety-expansion part will receive the highest safe dose identified in the safety-expansion part. The purpose of the safety-expansion part of the study is to determine how well LDE225 is tolerated, what the side effects are, and whether it causes the tumor to shrink. If your child participates in the study, they will be asked to come to the study site for about 12 visits during the first 8 weeks of receiving study drug (Cycles 1 and 2) and about 2 visits during each subsequent 4 weeks of study drug administration (Cycle 3 onwards). Each visit should last a few hours, but two of the visits in Cycle 1 may last most of the day (up to 8 hours or more) because timed blood samples are needed.
06/20/2013 04:02 AM