E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of imatinib in combination with hydroxyurea (HU) plus initial radiotherapy (RT) after surgery in patients with newly diagnosed glioblastoma multiforme (GBM) who are receiving or who are not receiving EIACD in phase I. |
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E.2.2 | Secondary objectives of the trial |
1. To characterize the safety and tolerability of imatinib in combination with HU plus initial RT after surgery, including acute and chronic toxicities, in these patient populations. 2. To characterize the single-dose and repeated-dose pharmacokinetic assessments of imatinib and HU combination therapy in these patient populations. 3. At MTD dose level expansion: • To evaluate preliminary efficacy (overall response rates [RR], duration of response, progression-free survival (PFS) at 6 month , and overall survival) in these patient populations (in phase II).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients must have newly diagnosed uni- or bilocular glioblastoma multiforme (GBM) WHO °IV following partial or complete tumor resection. The results of a biopsy alone are not sufficient for diagnosis. The diagnosis of primary malignant glioma must be histologically confirmed. The original tissue paraffin block for each patient must be available for central diagnostic review. • MRI finding after surgery: (T1w axial, contrast agent dose 0,2ml/kg body weight; within 48h/ max. 72 hours) No evidence of contrast agent-accumulating residual tumor Or Contrast agent-accumulating residual tumor with a (maximal) Diameter ≤ 1,0 cm (RECIST) • Patients taking steroids: must have been on a stable dose for ≥ 7 days • ECOG performance score 2 • Hemoglobin ≥ 10g/dL (or hematocrit > 29%), ANC > 1,500 cells/l, platelets > 100,000 cells/l. • Serum creatinine < 1.5 mg/dl, BUN < 25 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal. • Male and female patients with age ≥ 18 years. • Male and female patients who are sexually active must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation. • Female patients of child bearing potential must have had a negative pregnancy test within 48 hours prior to visit 1 (start of study drug). • Patients with a life expectancy of at least 12 weeks • Signed informed consent by the patient prior to patient entry and any study procedure
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E.4 | Principal exclusion criteria |
• Patients who have ever received previous imatinib for any duration prior to study entry • Patients with ≥ grade 2 peripheral edema, or pulmonary or pericardial effusions or ascites of any grade. • Patients who have an excessive risk of an intracranial hemorrhagic event (defined by stroke within the prior 6 months, history of CNS (excluding post-operative grade 1) or intraocular bleed. • Patients who have any uncontrolled systemic infection. • Patients who have any concurrent severe and/or uncontrolled medical disease. • Patients with evidence of intra-tumor hemorrhage on pretreatment diagnostic imaging. • Patients who have had major surgery within 2 weeks prior to study entry, or who have not recovered from prior major surgery. • Patients who received chemotherapy prior to study start or other investigational agents (biological, immunotherapeutic or cytostatic agents) prior to study start. • Patients with an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of imatinib • Patients who are taking Coumadin (warfarin sodium). • For the purposes of MRI imaging, patients with a pacemaker; ferromagnetic metal implants other than those approved as safe for use in MR scanners (e.g. some types of aneurysm clips, shrapnel); patients suffering from uncontrollable claustrophobia or physically unable to fit into the machine (e.g. obesity etc.). • Patients with another primary malignancy treated within the prior three years except excised squamous cell carcinomas of the skin and carcinoma in situ lesions of other organs which have been treated for cure. • Patients with a known history of Human Immunodeficiency Virus (HIV) seropositivity; testing for HIV is not required at study entry. • Patients who are considered by the investigator as unlikely to be able to be compliant with the study, take the study medications, travel for the necessary assessment visits, or have other medical conditions likely to interfere with the study assessments must not be entered onto the trial. • Patients who are not able to provide reliable informed consent and who do not have a legal representative for healthcare decisions on their behalf must not be entered onto the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of imatinib in combination with hydroxyurea plus initial radiotherapy. |
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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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | 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 | 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 |