E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Glioblastoma multiforme and progression after prior VEGF-directed therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018337 |
E.1.2 | Term | Glioblastoma multiforme |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine the efficacy of this regimen, in terms of progression-free survival, in these patients. |
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E.2.2 | Secondary objectives of the trial |
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).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 < 1.0 OR 24-hour urine protein < 1,000 mg -Fasting cholesterol < 350 mg/dL (cholesterol medications are allowed) -Fasting triglycerides < 400 mg/dL -PT INR ≤ 1.5 -Hematocrit < 41% (for males) or < 38% (for females) -Fertile females must use oral contraceptive, IUD (intrauterine device) or preservatives. -Fertile males must use preservatives. |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Response rate (MacDonald) Time to progression Progression-free survival Overall survival Safety (CTCAE 3.0) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |