Phase I Trial of Intratumoral Administration of a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Best response using the World Health Organization response criteria
研究概览
简要总结
This phase I trial studies the side effects and the best dose of a vaccine therapy in treating patients with malignant peripheral nerve sheath tumor that cannot be removed by surgery (unresectable) or has come back after a period of improvement (recurrent). Vaccines made from a gene-modified virus may kill tumor cells expressing a gene called neurofibromin 1 (NF1) without affecting surrounding normal cells and may also help the body build an effective immune response to kill tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of intratumoral administration of an Edmonston strain measles virus genetically engineered to express neurofibromatosis type 1 (NIS) (oncolytic measles virus encoding thyroidal sodium iodide symporter [MV-NIS]) in patients with inoperable or recurrent malignant peripheral nerve sheath tumor (MPNST).
II. To determine the safety and toxicity of intratumoral administration of MV-NIS in patients with inoperable recurrent MPNST.
III. To preliminarily assess antitumor efficacy of intratumoral MV-NIS administration by the rate of progression-free survival at 3 months, achieved by following radiographic response of the treated lesion using World Health Organization (WHO) response criteria guidelines.
SECONDARY 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
- •Age >= 18 years
- •Pathologically confirmed MPNST, with or without underlying diagnosis of neurofibromatosis type 1 (diagnostic criteria for neurofibromatosis type 1)
- •Measurable disease as defined by at least one tumor that is measurable in two dimensions on CT or magnetic resonance imaging (MRI) scan (minimum size 1.0 cm for at least one lesion)
- •MPNST for which standard therapy is not curative, including patients with surgically unresectable lesions, progression (WHO criteria) or recurrence of an MPNST in a previously radiated field (if it has been at least 4 weeks prior to registration since the last dose of radiation); Note: patients with metastatic disease also are eligible for participation
- •Patient may have more than one site of recurrent or metastatic disease but only one lesion that is >= 1 cm in size will be injected (if in the lung, the lesion must be >= 2 cm and adjacent to the pleura in the lung)
- •Absolute neutrophil count (ANC) >= 1500
- •Platelet (PLT) >= 100,000
- •Hemoglobin (HgB) >= 9.0 g/dL
- •Total bilirubin =< institutional upper limit of normal (ULN)
- •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x upper limit of normal (ULN)
- •Creatinine =< 1.0 mg/dL
- •International normalized ratio (INR) =< 2.0
- •Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- •Provide informed written consent
- •Willingness to return to Mayo Clinic Rochester for follow-up
- •Willingness to provide biologic samples for correlative research purposes
- •Life expectancy >= 12 weeks
- •Cluster of differentiation (CD)4 count >= 200/uL or >= 15% of peripheral blood lymphocytes
- •Ability to complete questionnaire(s) by themselves or with assistance
排除标准
- •Any of the following
- •Pregnant women
- •Nursing women
- •Men or women of childbearing potential who are unwilling to employ adequate contraception during treatment and 8 weeks following the completion of treatment
- •Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- •Receiving therapeutic anticoagulation (Coumadin or low molecular weight heparin, heparin, apixaban, dabigatran, rivaroxaban, warfarin)
- •Active infection =< 5 days prior to registration
- •History of tuberculosis or history of purified protein derivative (PPD) positivity
- •Any of the following prior therapies:
- •Chemotherapy =< 3 weeks prior to registration
- •Immunotherapy =< 4 weeks prior to registration
- •Biologic therapy =< 4 weeks prior to registration
- •Radiation therapy =< 3 weeks prior to registration
- •Failure to fully recover from acute, reversible effects defined as =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.0 of prior chemotherapy regardless of interval since last treatment except alopecia and neuropathy
- •Requiring blood product support
- •Patient has central nervous system (CNS) metastases or seizure disorder. Note: Patients with seizures controlled by medication are eligible.
- •Human immunodeficiency virus (HIV)-positive test result or history of other immunodeficiency
- •History of organ transplantation
- •History of chronic hepatitis B or C
- •Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- •Treatment with oral/systemic corticosteroids, with the exception of topical or inhaled steroids
- •Current exposure to household contacts =< 15 months old or household contact with known immunodeficiency; NOTE: patient must avoid contact during documented viral shedding; participants with continuous viral shedding will be given recommendations for restricted activities to avoid contact with immunocompromised persons
- •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
- •Allergy to lidocaine, fentanyl, midazolam, or propofol (may be used during tumor biopsy or injection)
研究组 & 干预措施
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Computed Tomography (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter (Biological)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Quality-of-Life Assessment (Other)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Single Photon Emission Computed Tomography (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Ultrasound Imaging (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Biopsy (Procedure)
Treatment (MV-NIS)
Patients receive MV-NIS intratumorally on day 1. Patients also undergo SPECT/CT at baseline and at 3 and 8 days after MV-NIS. Patients may also undergo SPECT/CT at 15 and 28 days, and at 6 weeks based on whether there is uptake on prior imaging studies. Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Best response using the World Health Organization response criteria
时间窗: From the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started), assessed up to 2 years
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and dose level).
Maximum tolerated dose defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience dose-limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experience DLT
时间窗: 6 weeks
Assessed according to according to Common Terminology Criteria for Adverse Events version 4.0. The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.
Incidence of adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
时间窗: Up to 2 years after treatment
The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
次要结局
- Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines(At 3 months)
- Absolute percentage change in quality of life measured using the Brief Pain Inventory (short form) and Brief Fatigue Inventory(Baseline to up to 2 years)
- Incidence of measles virus shedding/persistence following intratumoral administration(Up to 2 years)
- Viral gene expression(Up to 2 years)
- Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging(Up to day 8)
- Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography/computed tomography(Baseline to up to day 8)
- Growth-rate between treated and untreated lesions(Up to 2 years)
- Humoral and cellular immune response to the injected virus(Up to 2 years)
- Incidence of viral replication following intratumoral administration(Up to 2 years)
- Incidence of viremia following intratumoral administration(Up to 2 years)
- Time to progression(Up to 2 years)
- Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)(Up to 2 years)