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

Neurofibromatosis Type 1 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02700230
• Other study ID #: MC1372
• Secondary ID: NCI-2016-00179MC
• Status: Recruiting
• Phase: Phase 1
• Start date: March 22, 2017
• Est. completion date: September 14, 2024

Study information

• Verified date: January 2024
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 14, 2024
• Est. primary completion date: September 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Metastatic Malignant Peripheral Nerve Sheath Tumor
• Neoplasms
• Nerve Sheath Neoplasms
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1
• Recurrence
• Recurrent Malignant Peripheral Nerve Sheath Tumor

Intervention

Procedure:
• Computed Tomography
Undergo CT scan

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Oncolytic Measles Virus Encoding Thyroidal Sodium Iodide Symporter
Given intratumorally

Other:
• Quality-of-Life Assessment
Ancillary studies

Procedure:
• Single Photon Emission Computed Tomography
Undergo SPECT imaging
• Magnetic Resonance Imaging
Undergo MRI
• Ultrasound Imaging
Undergo ultrasound imaging
• Biospecimen Collection
Undergo blood sample collection
• Biopsy
Undergo tissue biopsy

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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
Primary	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.	Up to 2 years after treatment
Primary	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.	6 weeks
Secondary	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.	Baseline to up to 2 years
Secondary	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.	Baseline to up to day 8
Secondary	Growth-rate between treated and untreated lesions	Differences in growth-rate between treated and untreated lesions will be compared using paired t-tests.	Up to 2 years
Secondary	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).	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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).	At 3 months
Secondary	Time to progression		Up to 2 years
Secondary	Time until hematologic nadirs (absolute neutrophil count, platelets, hemoglobin)		Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to day 8

External Links

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