A Phase I/II Safety and Exploratory Pharmacodynamic Study of Intravenous Temsirolimus (CCI-779) in Pediatric Subjects with Relapsed/Refractory Solid Tumors

• Conditions: Relapsed/refractory neuroblastoma, high-grade glioma, and rhabdomyosarcoma.; MedDRA version: 9.1Level: LLTClassification code 10018338Term: Glioma; MedDRA version: 9.1Level: LLTClassification code 10029260Term: Neuroblastoma; MedDRA version: 9.1Level: LLTClassification code 10039022Term: Rhabdomyosarcoma

• Registration Number: EUCTR2007-000371-42-DE
• Lead Sponsor: Wyeth Research Division of Wyeth Pharmaeuticals Inc. (A Pfizer Company)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 95

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 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
Histologic confirmation is required at time of initial diagnosis and not at time or replase. Histological confirmation is not required for brain stem gliomas.

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 3 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 Platelet count must not be transfusion dependent), 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 as referenced in Attachment 5) >= lower limit for age, or
-serum creatinine concentration <=2x normal for age.
10.Adequate hepatic function: Bilirubin <=1.5 x institutional upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 x institutional ULN.
11.Life expectancy of at least 2 months.
12.Subjects of childbearing potential or with partners of childbearing potential must be willing to use a reliable method of birth control during entire course of study and for 12 weeks after study completion.
13.Signed and dated, Independent Ethics Committee or institutional review board (IRB) approved informed consent form (and documented assent for subjects of appropriate age as required by each institution or local regulation) before any screening procedures not considered standard-of-care are performed

Are the trial subjects under 18? yes
Number of subjects for this age

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.History of known 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 temsirolimus or any of the components (refer to Attachment 4 for details of components) or other medical reasons for not being able to receive adequate pre-medication (e.g. antihistamine such as diphenhydramine).
11.Unwillingness or inability to comply with procedures required in this protocol

Study & Design

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