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Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery

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ClinicalTrials.gov Identifier: NCT02700230
Recruitment Status : Recruiting
First Posted : March 7, 2016
Last Update Posted : June 18, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE February 25, 2016
First Posted Date  ICMJE March 7, 2016
Last Update Posted Date June 18, 2021
Actual Study Start Date  ICMJE December 8, 2017
Estimated Primary Completion Date June 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
  • 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).
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
  • Best response using the WHO 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).
  • Incidence of adverse events according to the National Cancer Institute CTCAE v. 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.
  • MTD 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 according to CTCAE v. 4.0 [ Time Frame: 6 weeks ]
    The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2017)
  • Absolute percentage change in quality of life measured using the Brief Pain Inventory (short form) and Brief Fatigue Inventory [ Time Frame: Baseline to up to 2 years ]
    Determination of significant changes in quality of life over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. Quality of life will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in quality of life scores over time as well as associations between change in quality of life scores at different time points and per dose level.
  • Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography/computed tomography [ Time Frame: Baseline to up to day 8 ]
    Patients may be imaged on days 15, 28 and week 6. Absolute and percent change from baseline along with t-tests to evaluate change from baseline to all observed timepoints.
  • Growth-rate between treated and untreated lesions [ Time Frame: Up to 2 years ]
    Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
  • Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
    Correlations between these laboratory values and other outcome measures will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Incidence of measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
  • Incidence of viral replication following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
  • Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
  • Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines [ Time Frame: At 3 months ]
    A progression-free survival at 3 months success is defined as a patient who is alive and their treated lesion is progression free at three months after they have treatment with oncolytic measles virus encoding thyroidal sodium iodide symporter (MV-NIS).
  • Time to progression [ Time Frame: Up to 2 years ]
  • Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin) [ Time Frame: Up to 2 years ]
  • Viral gene expression [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
  • Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging [ Time Frame: Up to day 8 ]
    Patients may be imaged on days 15, 28 and week 6. Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Absolute and percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
  • Absolute percentage change in quality of life (QOL) measured using the Brief Pain Inventory (short form) [ Time Frame: Baseline to up to 2 years ]
    Determination of significant changes in QOL over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. QOL will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in QOL scores over time as well as associations between change in QOL scores at different time points and per dose level.
  • Absolute percentage change in quality of life (QOL) measured using the Brief Fatigue Inventory [ Time Frame: Baseline to up to 2 years ]
    Determination of significant changes in QOL over time will be assessed using a signed rank test comparing the change at each assessment point from baseline. QOL will be used as a descriptive supplement to other clinical information. Simple exploratory analysis may be undertaken to look for changes in QOL scores over time as well as associations between change in QOL scores at different time points and per dose level.
  • Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using SPECT/CT [ Time Frame: Baseline to up to week 6 ]
    Patients may be imaged on days 15, 28 and week 6. Absolute change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
  • Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using SPECT/CT [ Time Frame: Baseline to up to week 6 ]
    Patients may be imaged on days 15, 28 and week 6. Percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
  • Growth-rate between treated and untreated lesions [ Time Frame: Up to 2 years ]
    Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.
  • Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
    Correlations between these laboratory values and response will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Humoral and cellular immune response to the injected virus [ Time Frame: Up to 2 years ]
    Correlations between these laboratory values and dose levels will be carried out by standard parametric and nonparametric correlation procedures (Pearson's and Spearman's coefficients).
  • Incidence of measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and response will be carried out in an exploratory manner.
  • Incidence of measles virus shedding/persistence following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and dose levels will be carried out in an exploratory manner.
  • Incidence of viral replication following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response, and dose levels will be carried out in an exploratory manner.
  • Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and response will be carried out in an exploratory manner.
  • Incidence of viremia following intratumoral administration [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and dose levels will be carried out in an exploratory manner.
  • Progression-free survival (PFS) by radiographic response of the treated lesion using WHO response criteria guidelines [ Time Frame: At 3 months ]
    A PFS3 success is defined as a patient who is alive and their treated lesion is progression free at three months after they have treatment with MV-NIS.
  • Time to progression [ Time Frame: Up to 2 years ]
  • Time until hematologic nadirs (ANC) [ Time Frame: Up to 2 years ]
  • Time until hematologic nadirs (Platelets) [ Time Frame: Up to 2 years ]
  • Time until hematologic nadirs (Hemoglobin) [ Time Frame: Up to 2 years ]
  • Viral gene expression [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and response will be carried out in an exploratory manner.
  • Viral gene expression [ Time Frame: Up to 2 years ]
    Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and dose levels will be carried out in an exploratory manner.
  • Virus elimination as monitored by SPECT/CT imaging [ Time Frame: Up to week 6 ]
    Patients may be imaged on days 15, 28 and week 6. Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Percent change from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
  • Virus elimination as monitored by SPECT/CT imaging [ Time Frame: Up to week 6 ]
    Patients may be imaged on days 15, 28 and week 6. Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Absolute from baseline along with t-Tests to evaluate change from baseline to all observed timepoints.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery
Official Title  ICMJE 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
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.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Malignant Peripheral Nerve Sheath Tumor
  • Neurofibromatosis Type 1
  • Recurrent Malignant Peripheral Nerve Sheath Tumor
Intervention  ICMJE
  • Procedure: Computed Tomography
    Undergo CT scan
    Other Names:
    • CAT
    • CAT Scan
    • Computerized Axial Tomography
    • Computerized Tomography
    • CT
    • CT SCAN
    • tomography
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
    Given intratumorally
    Other Name: MV-NIS
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Procedure: Single Photon Emission Computed Tomography
    Undergo SPECT imaging
    Other Names:
    • Medical Imaging, Single Photon Emission Computed Tomography
    • Single Photon Emission Tomography
    • single-photon emission computed tomography
    • SPECT
    • SPECT imaging
    • SPECT SCAN
    • SPET
    • tomography, emission computed, single photon
    • Tomography, Emission-Computed, Single-Photon
Study Arms  ICMJE Experimental: 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.
Interventions:
  • Procedure: Computed Tomography
  • Other: Laboratory Biomarker Analysis
  • Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
  • Other: Quality-of-Life Assessment
  • Procedure: Single Photon Emission Computed Tomography
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 1, 2016)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 15, 2022
Estimated Primary Completion Date June 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

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
    • 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
  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02700230
Other Study ID Numbers  ICMJE MC1372
NCI-2016-00179 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1372 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Dusica Babovic-Vuksanovic Mayo Clinic
PRS Account Mayo Clinic
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP