Clinical Trials

OBJECTIVES:

     Primary

       -  To determine if maintenance therapy with pemetrexed disodium versus observation improves progression-free survival of patients with malignant pleural mesothelioma who have at least stable disease after completion of first-line therapy comprising pemetrexed disodium with cisplatin or carboplatin.

     Secondary

       -  To determine the overall survival of patients treated with this regimen versus observation.

       -  To evaluate the frequency of responses in patients treated with this regimen.

       -  To assess the toxicity of this regimen in these patients.

     OUTLINE: This is a multicenter study. Patients are stratified according to first-line chemotherapy regimen (cisplatin/pemetrexed disodium vs carboplatin/pemetrexed disodium), histologic subtype (epithelioid vs other) and number of courses received (< 6 vs 6).

       -  Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

       -  Arm II: Patients undergo observation until disease progression. After completion of study therapy, patients are followed up every 6 months for 3 years.

PRIMARY OBJECTIVES:

     Maximum tolerated dose (MTD) for the intrapleural administration of a modified vaccine strain measles virus (MV) genetically engineered to produce human thyroidal sodium iodine symporter (NIS) (MV-NIS [oncolytic measles virus encoding thyroidal sodium iodide symporter])in patients with MPM.

     SECONDARY OBJECTIVES:

     Safety and toxicity of the repeated (up to 6 cycles) intrapleural administration of MV-NIS in patients with malignant pleural mesothelioma.

     TERTIARY OBJECTIVES:

     I. Time course of viral infection, dissemination and elimination by non-invasive measurements of NIS gene expression using radioactive iodine and single-photon emission computed tomography (SPECT)/ computed tomography (CT) imaging with.

     II. Viremia, viral replication, and viral shedding following intrapleural administration.

     III. Changes in humoral and cellular anti-MV immunity following the intrapleural administration of MV-NIS.

     IV. Antitumor efficacy of this approach by serial measurements of radioiodine uptake by SPECT/CT, radiographic response, and time to disease progression.

     V. Changes in both local and systemic innate and adaptive anti-tumor immunity following the intrapleural administration of MV-NIS.

     VI. Effect of MV-NIS administration on the eukaryotic initiation factor (eIF) 4F translation complex in mesothelioma cells.

     OUTLINE: This is a dose-escalation study.

     Patients receive the oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS) intrapleurally. In the absence of unacceptable side effects or disease progression treatment can be repeated every 28 days for up to 6 courses.

     After completion of study treatment, patients are followed up every 3 to 6 months for up to 5 years.

Mesothelioma is a cancer that develops from serosal surfaces usually in response to prior asbestos exposure. A history of asbestos exposure can be elicited in more than 80% of mesothelioma victims. However, asbestos exposure alone is not sufficient to cause the development of mesothelioma. Nearly 27 million individuals in the US, were exposed to asbestos in the work place between 1940 and 1979 but just 3,000 new cases of mesothelioma are diagnosed each year. Therefore, the investigators hypothesis is that genetic variation in addition to asbestos exposure, and host factors contribute to the development of mesothelioma. It is estimated, based on the investigators preliminary studies, that a population in excess of 1,000 subjects with mesothelioma is required to perform a valid GWAS. Therefore a multicenter approach is necessary to collect data and DNA on sufficient numbers with mesothelioma to adequately evaluate genetic risk. It is the aim of this proposal to develop a consortium of mesothelioma investigators to share phenotypic data and DNA samples and to perform genome wide association scanning (GWAS).