Relapsed/refractory neuroblastoma,high-grade glioma, and rhabdomyosarcoma. MedDRA version: 9.1 Level: LLT Classification code 10018338 Term: Glioma MedDRA version: 9.1 Level: LLT Classification code 10029260 Term: Neuroblastoma MedDRA version: 9.1 Level: LLT Classification code 10039022 Term: Rhabdomyosarcoma
Conditions
Interventions
Product Name: Temsirolimus IV
Product Code: CCI-779
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Temsirolimus
CAS Number: 162635043
Current Sponsor code: CCI-779
Con
Sponsors
Wyeth Research Division of Wyeth Pharmaeuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1 only: (Now closed) 1. Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system [CNS] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brains team gliomas and optic pathway tumors). 2. Evaluable disease. Part 2 only: 1. Subjects with a histologically confirmed diagnosis of refractory or relapsed: - Neuroblastoma - High-grade gliomas: gliobalstoma multiforme, anaplastic astrocytmas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas) - Rhabdomyosarcoma 2. Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted). Part 1 and Part 2: 1. At least 3 months since prior autologous or allogenic bone marrow transplantation (BMT) or stem cell transplant (SCT) at the time of study entry. 2. Prior Radiotherapy: - at least 2 weeks since prior local radiation therapy at the time of study entry - at least 3 months since prior craniospinal radiotherapy at the time of study entry - at least 6 months since prior radiotherapy to: whole abdomen or pelvis, whole lungs, >25% of bone marrow reserve, or total body irradiation at the time of study entry 3. At least 3 weeks since prior chemotherapy (6 weeks since nitrosoureas) at the time of study entry 4. At least 3 weeks since prior immunotherapy at the time of study entry 5. At least 3 weeks since any other prior investigational therapy at the time of study entry. Investigational therapy is defined as treatment that is not approved for any indication 6. Age: 1-21 years or up to pediatric age limit as defined by local regulations at the time of study entry 7. Lansky performance status 60%-100% for subjects aged 1 to 10 or Karnofsky performance status 60%-100% for subjects aged 11 to 21 or up to pediatric age limit as defined by local regulations 8. Absolute Neutrophil Count (ANC) >= 1,000/mm3, platelet count >=75,000/mm3 (>= 50,000/mm3 for subjects with bone marrow involvement), and hemoglobin (Hgb) >=8 g/dL (transfusion of packed red cells is permitted if subject is known to have bone marrow involvement). 9. Adequate renal function based on either of the following criteria: - creatinine clearance (estimated from the Schwartz formula) >= lower limit for age, or - serum creatinine concentration =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects known to be human immunodeficiency virus (HIV) positive 2. Active infection or serious intercurrent illness 3. Subjects with known hepatitis C or known active hepatitis B 4. Pulmonary hypertension or pneumonitis 5. Any other major illness which in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in this study 6. Concomitant therapy with any other investigational therapy 7. Subjects receiving enzyme-inducing anticonvulsants 8. Major surgery within 6 weeks prior to study entry 9. Pregnant or lactating women 10. Known hypersensitivity to any of the components in the temsirolimus infusion or other medical reasons for not being able to receive adequate pre-medication 11. Unwillingness or inability to comply with procedures required in this protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 (Part 1 is now closed): Primary Objective - To evaluate the safety of IV temsirolimus given once weekly to children with solid tumors with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. Part 2: Primary objective - To obtain preliminary information on the anti-tumor activity of IV temsirolimus in children with relapsed/refractory neuroblastoma, high-grade glioma, and rhabdomyosarcoma. Anti-tumor activity will be assessed by determining the percentage of subjects exhibiting objective response (CR + PR) within 12 weeks.;Secondary Objective: Part 1 (Part 1 is now closed): 1) To identify the maximum tolerated dose or a biologically effective dose of IV temsirolimus when administered once weekly. 2) To obtain preliminary information on the anti-tumor activity of IV temsirolimus. 3) To determine the single- and multiple-dose pharmacokinetics of temsirolimus in children with once-weekly IV treatment. 4) To determine the effects of IV temsirolimus on changes in the mTOR signaling pathway in the PBMCs. Part 2: 1) To verify the safety of the selected dose. 2) To evaluate the percentage of subjects exhibiting freedom from progression (disease stabilization defined as CR+VGPR+MR+PR+SD for subjects with neuroblastoma and CR+PR+SD for all other subjects) at 3 months. 3) To determine the multiple-dose pharmacokinetics of temsirolimus in children with once-weekly IV treatment. 4) To determine the effects of IV temsirolimus on changes in the mTOR signaling pathway in the bone marrow. ;Primary end point(s): The primary endpoint of Part 2 of this study is objective response (CR+PR) rate within 12 weeks. | — |
Countries
France, Germany, Poland
Outcome results
None listed