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Metastatic Malignant Peripheral Nerve Sheath TumorPhase 1NCT02700230

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

A Phase 1 study testing Computed Tomography, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter in people with Metastatic Malignant Peripheral Nerve Sheath Tumor and Neurofibromatosis Type 1, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Computed Tomography, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
22 Mar 2017to 17 Apr 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
  • The following laboratory values obtained =< 14 days prior to registration
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  • 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

Who cannot join

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
  • 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)
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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).

  1. 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.

Being tested
Computed Tomography, Laboratory Biomarker Analysis, Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter, Quality-of-Life Assessment, Single Photon Emission Computed Tomography
Medical subject headings
Neurofibrosarcoma, Neurofibromatosis 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography

    Undergo CT scan

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide SymporterBiological

    Also called MV-NIS

    Given intratumorally

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Single Photon Emission Computed TomographyProcedure or surgery

    Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, single-photon emission computed tomography, SPECT

    Undergo SPECT imaging

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR

    Undergo MRI

  • Ultrasound ImagingProcedure or surgery

    Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography

    Undergo ultrasound imaging

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • BiopsyProcedure or surgery

    Also called Bx

    Undergo tissue biopsy

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT02700230
Study groupRoleWhat they receive
Treatment (MV-NIS)ExperimentalPatients 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.
Receives: 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; Procedure: Magnetic Resonance Imaging; Procedure: Ultrasound Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Best response using the World Health Organization response criteria

    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).

    Measured: 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

  2. Incidence of adverse events according to the National Cancer Institute 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. 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.

    Measured: Up to 2 years after treatment

  3. 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

    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.

    Measured: 6 weeks

Secondary outcomes (12)

  1. Absolute percentage change in quality of life measured using the Brief Pain Inventory (short form) and Brief Fatigue Inventory

    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.

    Measured: Baseline to up to 2 years

  2. Change in biodistribution of virally infected cells at various time points after infection with MV-NIS using single photon emission computed tomography/computed tomography

    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.

    Measured: Baseline to up to day 8

  3. Growth-rate between treated and untreated lesions

    Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.

    Measured: Up to 2 years

  4. Humoral and cellular immune response to the injected virus

    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).

    Measured: Up to 2 years

  5. Incidence of measles virus shedding/persistence following intratumoral administration

    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.

    Measured: Up to 2 years

  6. Incidence of viral replication following intratumoral administration

    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.

    Measured: Up to 2 years

  7. Incidence of viremia following intratumoral administration

    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.

    Measured: Up to 2 years

  8. Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines

    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).

    Measured: At 3 months

  9. Time to progression

    Measured: Up to 2 years

  10. Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)

    Measured: Up to 2 years

  11. Viral gene expression

    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.

    Measured: Up to 2 years

  12. Virus elimination as monitored by single photon emission computed tomography/computed tomography imaging

    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.

    Measured: Up to day 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2016 (estimated)
  2. Study start22 Mar 2017
  3. Primary completion17 Apr 2024
  4. Study completion17 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02700230
Sponsor's protocol ID
MC1372
Other IDs
NCI-2016-00179, MC1372, W81XWH-15-1-0115, 15-008308
Status last verified
Sep 2024
First submitted
25 Feb 2016
Last updated
27 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hassan A, Pestana RC, Parkes A. Systemic Options for Malignant Peripheral Nerve Sheath Tumors. Curr Treat Options Oncol. 2021 Feb 27;22(4):33. doi: 10.1007/s11864-021-00830-7.

    PubMed 33641042

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Computed Tomography, Laboratory Biomarker Analysis and Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter in people with Metastatic Malignant Peripheral Nerve Sheath Tumor and Neurofibromatosis Type 1, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02700230, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2024; AzTrials last refreshed its copy on 6 Nov 2026.

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