E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Phase I/II study for patients with newly diagnosed glioblastoma testing nelfinavir in combination with radiotherapy and concomitant and adjuvant temozolomide |
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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 | 10018336 |
E.1.2 | Term | Glioblastoma |
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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 |
To assess safety, tolerability and activity of nelfinavir given neo-adjuvant and concomitant to radiotherapy and temozolomide in newly diagnosed GBM. |
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E.2.2 | Secondary objectives of the trial |
• To describe the possible effect of nelfinavir on functional imaging • To describe the activity of nelfinavir in vivo on blocking the AKTpathway.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histological confirmed glioblastoma multiforme at primary diagnosis • Tumours which do enhance on pre-operative imaging • Age >=18-65 • WHO performance status 0-2, RTOG- RPA class III-IV. • No recent (< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction) • Willing and able to comply with the study prescriptions • Have given written informed consent before patient registration • Patient able to tolerate full course of radiotherapy • No previous radiotherapy to the head and neck area. • Prior neurosurgery within 6 weeks of treatment • No previous irradiation of the brain. • No previous chemotherapy • No prior or concurrent medical condition which would make treatment difficult to complete. Medication with steroids is allowed (See concomitant treatment chapter). • No uncontrolled infectious disease • No use of terfenadine, astemizol, cisapride, sildenafil, lovastatin or simvastatin • No concurrent medication that is metabolized by the CYP3A4 isoenzyme and cannot be replaced with other equivalent medications for the period of the study: antiarrhythmics (amiodarone, quinidine), neuroleptics (pimozide), sedative/hypnotic agents (midazolam, triazolam), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), HMG-CoA reductase inhibitors (lovastatin, simvastatin, atorvastatin), rifampin, rifabutin, felodipine, nifedipine, and sildenafil or St. John's wort. • Adequate haematological, renal and hepatic function • Absence of known HIV infection, chronic hepatitis B or hepatitis C infection • Absence of any medical condition, which could interfere with oral medication intake (e.g., frequent vomiting, partial bowel obstruction) • All patients of reproductive potential (male and female) must use effective contraception for the whole duration of the treatment and until 6 months thereafter. Females must not be pregnant or lactating
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E.4 | Principal exclusion criteria |
the opposite of the above |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints phase I: To determine the MTD of nelfinavir as an adjuvant in the radiochemotherapy treatment in primary glioblastoma patients by assessing the incidence of any grade 3 or higher non-haematological or grade 4 or higher haematological acute toxicity (according to CTCAE v3.0), excluding toxicities that can be expected from the standard treatment of concomitant radiotherapy with temozolomide.
Primary endpoints phase II: Progression free survival at 6 months
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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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
No treatment with Nelfinavir |
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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.8.5 | The trial involves multiple Member States | No |
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 | Yes |
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 | |
E.8.9.1 | In the Member State concerned days | |