A Phase 1 Trial of Oncolytic Measles Virotherapy in Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Adverse event (AE) profile
研究概览
简要总结
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
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 exclusion criteria
- •Radiotherapy =< 4 weeks Failure to fully recover from acute, reversible effects of prior anti-cancer therapy regardless of interval since last treatment; NOTE: patients must have fully recovered from all acute, reversible toxicities (defined as Common Terminology Criteria for Adverse Events [CTCAE] 4.0 =< grade 1) associated with previous treatment
- •Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception
- •Any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA] approved indication and in the context of a research investigation) or any other treatment specifically for treating the current malignancy
- •Immunocompromised patients, including patients known to be HIV positive
- •Other active malignancy =< 2 years prior to pre-registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix
- •History of organ transplantation
- •Known hepatitis B or C
- •Treatment with oral/systemic corticosteroids; NOTE: with the exception of topical or inhaled steroids
- •Exposure to household contacts =<15 months old or household contact with a person with known immunodeficiency
- •Allergy to measles vaccine or history of severe reaction to prior measles vaccination
- •Allergy to iodine; NOTE: this does not include reactions to intravenous contrast materials
- •History of tuberculosis or purified protein derivative (PPD) skin test positivity
- •Inability or unwillingness to have pleural catheter placed
- •Requiring ongoing blood product support at time of pre-registration
结局指标
主要结局
Adverse event (AE) profile
时间窗: 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.
次要结局
- 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)