E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a prospective phase II study investigating well-known antimetabolite (doxorubicin) and antiepileptic (valproate) drugs, in combination, for the treatment of refractory or recurrent malignant mesothelioma for which no active treatment is available in this indication. |
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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 |
To determine, by an academical non-commercial trial, the response rate of the combination of valproate acid and doxorubicin in patients with unresectable malignant mesothelioma failing after at least one previous chemotherapy regimen including platinum derivatives according to local policy. |
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E.2.2 | Secondary objectives of the trial |
- to determine survival rates - to assess the toxicity of the combination of valproate acid and doxorubicin - to determine the value of the PET based response assessment. - to establish the prognostic value of FDG-PET. - to obtain tissue and serum samples for further biomarkers assessment |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histological diagnosis of malignant mesothelioma - Unresectable or inoperable malignant mesothelioma failing after at least one prior chemotherapy regimen including platinum derivatives (cisplatin or carboplatin) according to local policy. - At least one evaluable or measurable CT-lesion - Availability for participating in the detailed follow-up of the protocol - Signed informed consent.
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E.4 | Principal exclusion criteria |
- Patients who are candidates for surgery with curative intent - Patient who were previously treated with anthracyclin derivatives - Performance status < 60 on the Karnofsky scale - A history of prior malignant tumour, except non-melanoma skin cancer or in situ carcinoma of the cervix and cured malignant tumour (more than 5-year disease free interval) - A history of prior HIV infection - Polynuclear cells < 2,000/mm³ - Platelet cells < 100,000/mm³ - Abnormal coagulation tests (aPTT, PTT, prothrombin time) and/or decreased fibrinogen - Serum bilirubin >1.5 mg/100 ml - Transaminases more than twice the normal range - Serum creatinine > 1.5 mg/100 ml - Recent myocardial infarction (less than 3 months prior to date of diagnosis) - Congestive cardiac failure (ejectional fraction of the left ventricle < 50%) or uncontrolled cardiac arrhythmia - Uncontrolled infectious disease - Active epilepsy needing a specific treatment - Concomitant treatment with IMAO, carbamazepine, mefloquine, phenobarbital, primidone, phenytoïn, lamotrigine, zidovudine - Pregnancy or refusal to use active contraception - A known allergy to valproate acid and/or doxorubicin - Serious medical or psychological factors which may prevent adherence to the treatment schedule. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the response rate of the combination of valproate acid and doxorubicin in patients with unresectable malignant mesothelioma failing after at least one previous chemotherapy regimen including platinum derivatives according to local policy. |
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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 | No |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | 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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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16 evaluable patients need to be registered in the trial in a first step. Early closure should occur if there is less than 1 response among these first patients. Otherwise, inclusion of patients will be pursued until a total sample size of 41 patients. After this second step, the tested treatment will be rejected if less than 3 responding patients are observed.
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 3 |