Glioblastoma multiforme and progression after prior VEGF-directed therapy MedDRA version: 9.1 Level: LLT Classification code 10018337 Term: Glioblastoma multiforme
Conditions
Interventions
Trade Name: Torisel
Product Name: Temsirolimus
Product Code: CCI-779
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 162635043
Other descriptive name: TEMSIROLIMUS
Concentration
Sponsors
Rigshospitalet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Written informed consent -Histological verification of primary GBM and failure after radiotherapy and temozolomide (TMZ) previously treated with VEGF-directed therapy with bevacizumab -Previously received radiotherapy and temozolomide -More than 4 weeks since any of the following prior treatments: a: Chemotherapy (6 weeks for nitrosoureas or mitomycin C) b: Radiotherapy to nontarget lesions or lesions that are not to be biopsied c: VEGF-directed therapy (including bevacizumab) d: Investigational agents -More than 6 months since prior major surgery or open biopsy and recovered (only 6 weeks required if operation is for recurrent GBM) -No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of the following (with exception to enzyme-inducing anti-epileptic drugs, please see dosage adjustment for temsirolimus page 10): a: Temsirolimus b: Bevacizumab c: CYP450 isoenzymes -ECOG performance status 0-1 -WBC = 3,000 mm³ -Absolute neutrophil count = 1,500/mm³ -Platelet count = 100,000/mm³ -Bilirubin normal -AST and ALT = 2.5 times upper limit of normal -Creatinine normal OR creatinine clearance = 60 mL/min -Urine protein:creatinine ratio =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Clinically significant cardiovascular disease, including the following: -Cerebrovascular accident within the past 6 months -Transient ischemic attack within the past 6 months -Myocardial ischemia within the past 6 months -Myocardial infarction within the past 6 months -Other thromboembolic event within the past 6 months -Unstable angina within the past 6 months -Uncontrolled hypertension (i.e., hypertension despite maximal therapy) -New York Heart Association class II-IV heart disease -Congestive heart failure -Serious cardiac arrhythmia requiring medication -Clinically significant peripheral vascular disease -Uncontrolled intercurrent illness -Ongoing or active infection One of the following within the past 6 months: a: Abdominal fistula b. astrointestinal perforation c: Intra-abdominal abscess d Serious or nonhealing wound, ulcer, or bone fracture -Psychiatric illness or social situations that would preclude study compliance -Uncontrolled diabetes -Hemoglobin A1c > 7% -Concurrent nonstudy-related surgical procedures -Other concurrent anticancer agents or therapies -Significant traumatic injury within the past 28 days -History of allergic reactions to compounds of similar chemical or biological composition to temsirolimus or bevacizumab -Hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (e.g., infliximab) -Pregnancy or nursing -Patients previously intolerant to bevacizumab -Anticoagulant therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy of this regimen, in terms of progression-free survival, in these patients. ;Secondary Objective: 1. Describe the adverse event profile of this regimen in these patients. 2. Determine the objective tumor response rate (complete response and partial response) in patients with recurrent glioblastoma multiforme treated with temsirolimus and bevacizumab. 3. Compare pre- vs post-treatment measurements of biomarkers and vascular system/immune system parameters in patients treated with this regimen. 4. Correlate tumor and blood biomarkers with clinical response in these patients (VEGF, PTEN, Akt, p-Akt, p53). ;Primary end point(s): Response rate (MacDonald) Time to progression Progression-free survival Overall survival Safety (CTCAE 3.0) | — |
Countries
Denmark
Outcome results
None listed