EUCTR2010-019348-37-IT进行中（未招募）不适用
A phase 1 study of LDE225 in pediatric patients with refractory or recurrent medulloblastoma or other tumors potentially dependent on the Hedgehog signaling pathway - ND
适应症
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 24
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Patients aged = 12 months and < 18 years 2. 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). 3. Performance Status: • Karnofsky performance status score = 60% for patients >10 years of age (Table 7-2) • Lansky score = 50 for patients = 10 years of age (Table 7-3) Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. 4. Adequate renal function as defined by: • Either serum creatinine = 1.5 x upper limit of normal (ULN) for age, or • Creatinine clearance or radioisotope glomerular filtration rate (GFR) =1.17 mL/s/1.73 m2 5. Adequate liver function as defined by: • Bilirubin (sum of conjugated + unconjugated) = 1.5 x ULN for age • Serum alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGOT) = 5 x ULN for age • Serum albumin = 20 g/L 6. Adequate bone marrow function as defined as: • Peripheral absolute neutrophil count (ANC) = 1.0 x 109/L • Platelet count = 80 x 109/L • Hemoglobin (Hgb) = 90 g/L (may receive red blood cell [RBC] transfusions). Patients with a Hgb = 80 g/L are eligible if their anemia is unequivocally related to recent surgery (rather than suspected bone marrow suppression). 7. For females of child-bearing potential (reproductive or child-bearing potential for this study will be defined as per local site practice): a negative pregnancy test = 72 hours before starting study treatment is required. If sexually active, females of child bearing potential must use ‘highly effective’ methods of contraception for the study duration and for 3 months following the last dose of LDE225. See section 5.1 of the protocolo for the highly effective methods of contraception. 8. For males of reproductive potential: any sexually active male patient must use a condom while on study treatment and for 3 months following the last dose of LDE225. Reproductive or child-bearing potential for this study will be defined as per local site practice. 9. Written informed consent/assent before any study-specific procedures (routine procedures performed as part of standard clinical care are permitted). Consent will be obtained from parent(s) or legal guardians and the signature of at least 1 parent or guardian will be required. Investigators will also obtain assent of patients according to local, regional or national guidelines. 10. All patients must consent to provide a tumor sample (archival or fresh) for analyses of expression of specific Hh pathway genes and mutations in Smo and PTCH. The tumor material submitted for these analyses may have been obtained at any time during the course of the patient’s disease. It is accepted that it may not be possible to obtain all samples before commencement of study-related treatment. It is also accepted that it may not be possible to obtain a sample for every patient (eg, if sufficient sample does not exist), and in this situation inclusion of the patient should be discussed with Novartis (as this may not make a patient ineligible).
- •Are the trial subjects under 18? yes
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) no
- •F.1.2.1 Number of subjects for this age range
- •F.1.3 Elderly (>=65
排除标准
- •1. Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies). 2. 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. 3. Investigational agents within 2 weeks or = 5 x t1/2 (whichever is longer) before start of study therapy. 4. Unresolved toxicity greater than CTCAE grade 1 from previous anticancer therapy or radiation therapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopeniaa 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. aInclusion of a patient with ongoing lymphopenia > CTCAE grade 1 from prior therapy must be first discussed and agreed with the Novartis physician. 5. Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 (listed in Post-Text-Supplement 3), or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices (listed in Post-Text-Supplement 3), that cannot be discontinued at least 1 week before start of study therapy, and for the duration of the study. 6. Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms, dose must have been stabilized (or decreasing) for at least 7 days before initiating study therapy. 7. Patients receiving treatment with any enzyme-inducing anticonvulsant (listed in Post- Text-Supplement 3), that cannot be discontinued at least 1 week before start of study therapy, and for the duration of the study. Patients on nonenzyme-inducing anticonvulsants are eligible. 8. Major surgery, serious illness, or traumatic injury within 2 weeks of starting study therapy. Insertion of a gastric feeding tube (G-tube), 3rd ventriculostomy, ventriculoperitoneal (VP) shunt and central venous access are not considered major surgery. 9. Surgery for revision of an allograft within 3 months of starting study therapy. 10. Patients anticipated to require major surgery within the first 2 cycles of treatment. 11. Patients who require a nasogastric tube for drug administration (G-tubes are permitted) 12. Any concurrent severe and/or uncontrolled medical conditions (eg, uncontrolled diabetes, uncontrolled diarrhea, autoimmune disease including lupus, psoriasis, inflammatory bowel disease, severe infection, severe hypertension or severe cardiovascular disease or clinically significant ECG abnormalities) that in the investigator’s opinion could put the patient at greater risk for treatment-related toxicities or confound the interpretation of clinical outcomes. 13. Patients who have neuromuscular disorders that are associated with elevated CPK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy). 14. Impaired cardiac function or clinically significant heart disease, including any one of the following: • Clinically significant heart disease (eg, congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) • QTc interval corrected for heart rate using Fridericia’s formula [QTcF] > 450 msec for males an
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