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

This study has suspended participant recruitment.
(Enrollment to Dose Level 1 is complete)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02700230
First Posted: March 7, 2016
Last Update Posted: September 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
  Purpose
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.

Condition Intervention Phase
Metastatic Malignant Peripheral Nerve Sheath Tumor Neurofibromatosis Type 1 Recurrent Malignant Peripheral Nerve Sheath Tumor 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 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Anticipated Study Start Date: October 2017
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02700230


Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Dusica Babovic-Vuksanovic Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02700230     History of Changes
Other Study ID Numbers: MC1372
NCI-2016-00179 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1372 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: February 25, 2016
First Posted: March 7, 2016
Last Update Posted: September 11, 2017
Last Verified: December 2016

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Neoplasms
Neurofibromatoses
Neurofibroma
Neurofibromatosis 1
Nerve Sheath Neoplasms
Neurilemmoma
Neurofibrosarcoma
Neoplasms, Nerve Tissue
Neoplasms by Histologic Type
Neoplastic Syndromes, Hereditary
Neurocutaneous Syndromes
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Peripheral Nervous System Neoplasms
Nervous System Neoplasms
Peripheral Nervous System Diseases
Neuromuscular Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neuroma
Fibrosarcoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma


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