Last updated on September 2011

Immunotoxin Therapy Pemetrexed and Cisplatin in Treating Patients With Malignant Pleural Mesothelioma That Cannot Be Removed by Surgery


Brief description of study

RATIONALE: Immunotoxins can find tumor cells and kill them without harming normal cells. Drugs used in chemotherapy, such as pemetrexed and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with immunotoxin therapy may kill more malignant mesothelioma cells. PURPOSE: This phase I trial is studying the side effects and best dose of immunotoxin therapy when given together with pemetrexed and cisplatin in treating patients with malignant pleural mesothelioma that cannot be removed by surgery.

Detailed Study Description

OBJECTIVES: Primary - To estimate the maximum-tolerated dose (MTD) of SS1(dsFv)-PE38 immunotoxin when administered with pemetrexed disodium and cisplatin and to establish a safe dose, based on the MTD for subsequent clinical testing (phase II recommended dose) in patients with unresectable malignant epithelial pleural mesothelioma. - To characterize the toxicity profile of SS1(dsFv)-PE38 immunotoxin. - To study the clinical pharmacology (i.e., pharmacokinetics) which may dictate modification of SS1(dsFv)-PE38 immunotoxin schedule and administration in future studies. - To observe antitumor activity, if any, especially in patients who receive SS1(dsFv)-PE38 immunotoxin at or near the MTD (or phase II recommended dose). Secondary - To monitor antibody formation to SS1(dsFv)-PE38 immunotoxin and to assess the impact of these antibodies on SS1(dsFv)-PE38 immunotoxin pharmacokinetics (PKs). - To investigate the potential of soluble mesothelin levels to predict PKs or any therapeutic or toxic response. - To perform a pilot assessment of a validated quality-of-life instrument. OUTLINE: This is a multicenter, dose-escalation study of SS1(dsFv)-PE38 immunotoxin. Patients receive SS1(dsFv)-PE38 immunotoxin IV over 30 minutes on days 1, 3, and 5, pemetrexed disodium IV over 10 minutes on day 1, and cisplatin IV over 2 hours on day 1 in courses 1 and 2. Beginning in course 3 and all subsequent courses, patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Monocytes are collected via apheresis after the first course to identify and remove T-cell epitopes in the immunotoxin protein for the design and production of less immunogenic immunotoxins in the future. Patients also undergo blood sample collection at baseline, before course 2, and day 21 of course 2 for laboratory and pharmacokinetic studies. Samples are analyzed for the presence of anti-SS1(dsFv)-PE38 immunotoxin antibodies using a study drug-specific immunoassay and for concentrations of circulating mesothelin using enzyme-linked immunosorbent assay. Tumor cells from archival paraffin-block biopsy specimens are analyzed for expression of mesothelin via immunohistochemistry. Patients complete a quality-of-life questionnaire (i.e., LCSS-MESO) at baseline, after course 2, and subsequently after every even course to assess symptoms including appetite loss, fatigue, cough, dyspnea, and pain. After completion of study treatment, patients are followed up at 1, 3, 6, 12, 15, 18, 21, and 24 months.

Clinical Study Identifier: NCT00575770

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Recruitment Status: Open


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