Recurrent Malignant Mesothelioma, Stage IA Malignant Mesothelioma, Stage IB Malignant Mesothelioma, Stage III Malignant Mesothelioma, Stage II Malignant Mesothelioma, Stage IV Malignant Mesothelioma
Conditions
Brief summary
This phase I clinical trial investigates the side effects and the best dose of local (intrapleural measles virus therapy in treating patients with malignant pleural mesothelioma (MPM). The investigators anticipate that the intrapleural of the vaccine strain measles virus will enable the virus to specifically infect and kill cancer cells and spare, without damaging normal cells. Furthermore, the investigators expect the measles virus to trigger an anti-tumor immune response which will result in additional destruction of the tumor by immune cells
Detailed description
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.
Interventions
Given intrapleurally
OTHERlaboratory biomarker analysis
Correlative studies
PROCEDUREsingle photon emission computed tomography
Correlative studies
PROCEDUREcomputed tomography
Correlative studies
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
PRE-REGISTRATION: * Diagnosis of MPM, confined to single pleural cavity, with histologic confirmation of the primary tumor * Measurable disease per modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for mesothelioma * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2 * Ability to provide informed consent * Willingness to return to Mayo Clinic Rochester or the University of Minnesota Cancer Center for follow up * Life expectancy \>= 12 weeks (in the opinion of the enrolling investigator) * Willingness to provide the biologic specimens and participate in the SPECT/CT imaging as required by the protocol * Presence of a pleural effusion with the ability to safely place an intrapleural catheter or have pre-existing intrapleural catheter * Absolute neutrophil count (ANC) \>= 1500/μL * Platelet count \>= 100,000/μL * Total bilirubin =\< 1.5 x upper limit of institutional normal * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 2 x upper limit of institutional normal * Serum Creatinine =\< 1.5 x upper limit of institutional normal * Hemoglobin \>= 9.0 g/dL * Must be willing to implement contraception throughout study and for the 4 weeks following last viral administration REGISTRATION: * Anti-measles immunity as demonstrated by serum IgG anti-measles antibody levels of ≥ 1.1 EU/ml as determined by BioPlex Measles IgG multiplex flow immunoassay. * Hepatitis B and C negative * Human immunodeficiency virus (HIV) negative * CD4 count \>= 200/μL * CT imaging review submission to confirm unilateral pleural involvement; this review for CT imaging is mandatory prior to registration to confirm eligibility; it should be initiated as soon as possible after pre-registration * Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
Exclusion criteria
PRE-REGISTRATION * Uncontrolled intercurrent illness including, but not limited to: * Active infection =\< 5 days prior to pre-registration * Psychiatric illness/social situations that would limit compliance with study requirements * Symptomatic congestive heart failure New York Heart Association classification III or IV * Symptomatic coronary artery disease (CAD) * Symptoms of CAD on systems review * Cardiac arrhythmias Any of the following therapies prior to pre-registration: * Chemotherapy =\< 4 weeks * Immunotherapy =\< 4 weeks * Biologic therapy =\< 4 weeks; Note exception: prior viral and/or gene therapy are
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event (AE) profile | 90 Days | The number and severity of toxicity incidents will indicate the level of tolerance for MV-NIS in the therapy of MPM. Non-hematologic toxicities will be evaluated via the CTCAE v4.0 standard toxicity grading. Hematologic toxicity measures such as anemia, neutropenia and thrombocytopenia will be assessed using continuous variables as the outcome measures (nadir and percent change from baseline values) as well as categorization via CTCAE v4.0 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Describe the safety of the intrapleural administration of MV-NIS in patients with malignant pleural mesothelioma for all cycles out to 90 days. | 90 Days | The number and severity of adverse events (AE) over the course of up to 6 cycles of MV-NIS therapy will indicate the level of tolerance for MV-NIS in the therapy of MPM. AE will be evaluated similar to the primary outcome via the CTCAE v4.0 standard toxicity grading and frequency distributions and other descriptive measures will form the basis of the analysis of these variables. |
Countries
United States
Outcome results
None listed