- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02700230
Vaccine Therapy in Treating Patients With Malignant Peripheral Nerve Sheath Tumor That is Recurrent or Cannot Be Removed by Surgery
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
Study Overview
Status
Conditions
Intervention / Treatment
- Other: Laboratory Biomarker Analysis
- Other: Quality-of-Life Assessment
- Other: Questionnaire Administration
- Procedure: Magnetic Resonance Imaging
- Procedure: Biospecimen Collection
- Procedure: Computed Tomography
- Procedure: Biopsy
- Procedure: Ultrasound Imaging
- Biological: Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
- Procedure: Single Photon Emission Computed Tomography
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
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Rochester, Minnesota, United States, 55905
- Recruiting
- Mayo Clinic
-
Contact:
- Clinical Trials Referral Office
- Phone Number: 855-776-0015
- Email: mayocliniccancerstudies@mayo.edu
-
Principal Investigator:
- Dusica Babovic-Vuksanovic, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
- 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. 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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
Patients also undergo MRI, ultrasound imaging, blood sample collection and tissue biopsy throughout the trial.
|
Correlative studies
Ancillary studies
Other Names:
Ancillary studies
Undergo MRI
Other Names:
Undergo blood sample collection
Other Names:
Undergo CT scan
Other Names:
Undergo tissue biopsy
Other Names:
Undergo ultrasound imaging
Other Names:
Given intratumorally
Other Names:
Undergo SPECT imaging
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
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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
|
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
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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.
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Up to 2 years after treatment
|
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.
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6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to progression
Time Frame: Up to 2 years
|
Up to 2 years
|
|
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.
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Baseline to up to 2 years
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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.
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Baseline to up to day 8
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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.
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Up to 2 years
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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).
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Up to 2 years
|
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.
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Up to 2 years
|
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.
|
Up to 2 years
|
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.
|
Up to 2 years
|
Progression-free survival by radiographic response of the treated lesion using World Health Organization response criteria guidelines
Time Frame: At 3 months
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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).
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At 3 months
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Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)
Time Frame: Up to 2 years
|
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.
|
Up to 2 years
|
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.
|
Up to day 8
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Dusica Babovic-Vuksanovic, M.D., Mayo Clinic
Publications and helpful links
General Publications
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Disease Attributes
- Genetic Diseases, Inborn
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Neoplasms, Nerve Tissue
- Peripheral Nervous System Diseases
- Nervous System Neoplasms
- Heredodegenerative Disorders, Nervous System
- Neoplastic Syndromes, Hereditary
- Neoplasms, Connective Tissue
- Sarcoma
- Neurocutaneous Syndromes
- Peripheral Nervous System Neoplasms
- Neoplasms, Fibrous Tissue
- Fibrosarcoma
- Neurofibroma
- Neoplasms
- Recurrence
- Neurofibromatoses
- Neurofibromatosis 1
- Nerve Sheath Neoplasms
- Neurofibrosarcoma
Other Study ID Numbers
- MC1372 (Other Identifier: Mayo Clinic)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2016-00179 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- W81XWH-15-1-0115 (Other Grant/Funding Number: Department of Defense)
- 15-008308 (Other Identifier: Mayo Clinic Institutional Review Board)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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