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

NCT ID: NCT02700230

Last Updated: 2024-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-22

Study Completion Date

2024-04-17

Brief Summary

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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

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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.

Conditions

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Metastatic Malignant Peripheral Nerve Sheath Tumor Neurofibromatosis Type 1 Recurrent Malignant Peripheral Nerve Sheath Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Intervention Type BIOLOGICAL

Given intratumorally

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Single Photon Emission Computed Tomography

Intervention Type PROCEDURE

Undergo SPECT imaging

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Ultrasound Imaging

Intervention Type PROCEDURE

Undergo ultrasound imaging

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Biopsy

Intervention Type PROCEDURE

Undergo tissue biopsy

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter

Given intratumorally

Intervention Type BIOLOGICAL

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Single Photon Emission Computed Tomography

Undergo SPECT imaging

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Ultrasound Imaging

Undergo ultrasound imaging

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Biopsy

Undergo tissue biopsy

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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CAT CAT Scan Computerized Axial Tomography Computerized Tomography CT CT SCAN tomography MV-NIS Quality of Life Assessment 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 Magnetic Resonance Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan Nuclear Magnetic Resonance Imaging NMRI Structural MRI sMRI 2-Dimensional Grayscale Ultrasound Imaging 2-Dimensional Ultrasound Imaging 2D-US Ultrasonography Ultrasound Ultrasound Test Ultrasound, Medical US Biological Sample Collection Biospecimen Collected Specimen Collection Bx

Eligibility Criteria

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

* 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 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)
* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dusica Babovic-Vuksanovic, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Rochester, Minnesota, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 33641042 (View on PubMed)

Related Links

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Other Identifiers

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NCI-2016-00179

Identifier Type: REGISTRY

Identifier Source: secondary_id

MC1372

Identifier Type: OTHER

Identifier Source: secondary_id

W81XWH-15-1-0115

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

15-008308

Identifier Type: OTHER

Identifier Source: secondary_id

MC1372

Identifier Type: -

Identifier Source: org_study_id

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