E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory glioblastoma multiforme. |
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MedDRA Classification |
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 |
Phase I:The main objective is to determine the maximum tolerated dose and recommended phase II dose of lapatinib when given in combination with temozolomide in patients with recurrent or refractory glioblastoma multiforme and to assess the safety, tolerability and toxicity profile of this regimen in these patients.Phase II:The primary objective is to evaluate the activity of lapatinib monotherapy in patients with recurrent high grade gliomas by determining possible metabolic changes in the brain. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include the evaluation of Clinical Benefit (SD, PR and CR) of lapatinib OD treatment (monotherapy or combination with temozolomide), as assessed by RECIST criteria and volumetric measurements, as well as Time to disease progression (TTP), survival (OS), toxicity and biomarker analysis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria:1. Written informed consent 2. Age ³18 years3. Radiographic evidence of recurrent glioma (Gr IV glioblastoma multiforme or Gr III anaplastic astrocytoma). Patients should have achieved CR, PR or SD with prior treatment with RT/ temozolomide (adjuvant or 1st line setting). Early recurrence patients may be included in the phase I study.4. Measurable disease at screening according to RECIST5. ECOG performance status (PS) 0-26. Adequate haematological function (ANC ≥1.5 x 109/L, Platelet count ≥100 x 109/L and Haemoglobin ≥9 g/dL)7. Adequate liver and renal function (Total bilirubin <1.5 x upper limit of normal, AST, ALT <2.5xULN in pts without liver metastases; <5xULN in pts with liver metastase, serum creatinine ≤1.25xULN or calculated creatinine clearance ≥50 mL/min)8. LVEF within institutional normal range9. All patients must have archived tumour tissue available for translational research – In a subset of suitable patients fresh tumour tissue will be obtained at screening by stereotactic biopsy and at week 4 of lapatinib treatment.10. Drugs and several herbal constituents (e.g. bergamontin and glabridin), which are inducers or inhibitors of CYP3A4 must not be taken within 10 days prior to initiation of treatment and are prohibited while the patient is being treated with lapatinib (a detailed list is provided in section 5.7)11. If a patient requires anticoagulant therapy the patient may remain on study but should be monitored carefully. |
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E.4 | Principal exclusion criteria |
Exclusion criteria:1. Pregnant or lactating women2. Clinically significant non-controlled cardiovascular disease 3. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment4. Prior treatment with EGFR inhibitors will not be allowed5. Known hypersensitivity to drugs chemically related to lapatinib 6. Evidence of any other disease, neurological or metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications7. Treatment with EIAEDs will be excluded, use of valproate will be permitted. 8. Patients will be excluded if unable to swallow tablets.9. Active infection. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Metabolic changes in the brain of patients by SPECT/PET-CT scans. |
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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 | 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 | Yes |
E.7.1.3.1 | Other trial type description |
Safety of combination therapy |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |