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
Overview
- Phase
- Phase 1
- Intervention
- Computed Tomography
- Conditions
- Metastatic Malignant Peripheral Nerve Sheath Tumor
- Sponsor
- Mayo Clinic
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Best response using the World Health Organization response criteria
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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: I. To determine the time course of viral gene expression and virus elimination and biodistribution of virally infected cells at various time points after infection with MV-NIS using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging. II. To assess viremia, viral replication, and measles virus shedding/persistence following intratumoral administration. III. To determine humoral and cellular immune response to the injected virus. IV. To assess the quality-of-life of patients treated with MV-NIS, using two inventories (Pain and Fatigue). V. To assess time to progression and differences in growth rates between treated and untreated tumor lesions. VI. To assess the overall survival time of patients treated with MV-NIS. OUTLINE: 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 magnetic resonance imaging (MRI), ultrasound imaging, blood sample collection and tissue biopsy throughout the trial. After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Computed Tomography
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
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.
Intervention: Quality-of-Life Assessment
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.
Intervention: Single Photon Emission Computed Tomography
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.
Intervention: Magnetic Resonance Imaging
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.
Intervention: Ultrasound Imaging
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.
Intervention: Biospecimen Collection
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.
Intervention: Biopsy
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.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Best response using the World Health Organization response criteria
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)