Phase II Study of Valproate and Doxorubicin in Malignant Mesothelioma

Study Overview
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Brief Summary
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The purpose of this study is to determine the response rate to the combination of doxorubicin and valproate acid in patients with MM failing after at least one previous chemotherapy regimen including platinum derivatives .

Official Title
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A Phase II Study Assessing the Activity of Valproate Acid Plus Doxorubicin in Refractory or Recurrent Malignant Mesothelioma

Conditions
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Malignant Mesothelioma

Intervention / Treatment
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* Drug: Valproate plus doxorubicin


Participation Criteria
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Eligibility Criteria
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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) At least one evaluable or measurable CT-lesion Availability for participating in the detailed follow-up of the protocol Signed informed consent 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Continuous oral administration of valproate plus every 3 weeks, intravenous administration of doxorubicin | Drug: Valproate plus doxorubicin<br>* Valproate 20-30 mg/kg orally (in order to obtain serum concentration between 50-100 mcg/ml) Doxorubicin 60 mg/m² intravenously every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | Every 3 courses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Survival will be dated from the day of registration until death or last follow up | 
| Toxicity |  | After each course of chemotherapy and at the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelioma, Valproate, Doxorubicin, Chemotherapy, Phase II