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A Phase 1 Trial of Oncolytic Measles Virotherapy in Mesothelioma

Phase 1
18 Years
Open (Enrolling)
Recurrent Malignant Mesothelioma, Stage IA Malignant Mesothelioma, Stage IB Malignant Mesothelioma, Stage II Malignant Mesothelioma, Stage III Malignant Mesothelioma, Stage IV Malignant Mesothelioma

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Trial Information

A Phase 1 Trial of Oncolytic Measles Virotherapy in Mesothelioma


Maximum tolerated dose (MTD) for the intrapleural administration of a modified vaccine
strain measles virus (MV) genetically engineered to produce human thyroidal sodium iodine
symporter (NIS) (MV-NIS [oncolytic measles virus encoding thyroidal sodium iodide
symporter])in patients with MPM.


Safety and toxicity of the repeated (up to 6 cycles) intrapleural administration of MV-NIS
in patients with malignant pleural mesothelioma.


I. Time course of viral infection, dissemination and elimination by non-invasive
measurements of NIS gene expression using radioactive iodine and single-photon emission
computed tomography (SPECT)/ computed tomography (CT) imaging with.

II. Viremia, viral replication, and viral shedding following intrapleural administration.

III. Changes in humoral and cellular anti-MV immunity following the intrapleural
administration of MV-NIS.

IV. Antitumor efficacy of this approach by serial measurements of radioiodine uptake by
SPECT/CT, radiographic response, and time to disease progression.

V. Changes in both local and systemic innate and adaptive anti-tumor immunity following the
intrapleural administration of MV-NIS.

VI. Effect of MV-NIS administration on the eukaryotic initiation factor (eIF) 4F translation
complex in mesothelioma cells.

OUTLINE: This is a dose-escalation study.

Patients receive the oncolytic measles virus encoding thyroidal sodium iodide symporter
(MV-NIS) intrapleurally. In the absence of unacceptable side effects or disease progression
treatment can be repeated every 28 days for up to 6 courses.

After completion of study treatment, patients are followed up every 3 to 6 months for up to
5 years.

Inclusion Criteria:


- Diagnosis of MPM, confined to single pleural cavity, with histologic confirmation of
the primary tumor

- Measurable disease per modified Response Evaluation Criteria in Solid Tumors (RECIST)
criteria for mesothelioma

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1, or 2

- Ability to provide informed consent

- Willingness to return to Mayo Clinic Rochester or the University of Minnesota Cancer
Center for follow up

- Life expectancy >= 12 weeks (in the opinion of the enrolling investigator)

- Willingness to provide the biologic specimens and participate in the SPECT/CT imaging
as required by the protocol

- Presence of a non-localized pleural effusion (layering on a lateral decubitus chest
x-ray [CXR] and absence of septations by thoracic ultrasound)

- Absolute neutrophil count (ANC) >= 1500/μL

- Platelet count >= 100,000/μL

- Total bilirubin =< 1.5 x upper limit of institutional normal

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =<
2 x upper limit of institutional normal

- Serum Creatinine =< 1.5 x upper limit of institutional normal

- Hemoglobin >= 9.0 g/dL

- Must be willing to implement contraception throughout study and for the 4 weeks
following last viral administration


- Anti-measles immunity as demonstrated by serum IgG anti-measles antibody levels of >=
20.0 EU/ml as determined by Enzyme Immunoassay

- Hepatitis B and C negative

- Human immunodeficiency virus (HIV) negative

- CD4 count >= 200/μL

- CT imaging review submission to confirm unilateral pleural involvement; this review
for CT imaging is mandatory prior to registration to confirm eligibility; it should
be initiated as soon as possible after pre-registration

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only

Exclusion Criteria:


- Uncontrolled intercurrent illness including, but not limited to:

- Active infection =< 5 days prior to pre-registration

- Psychiatric illness/social situations that would limit compliance with study

- Symptomatic congestive heart failure New York Heart Association classification

- Symptomatic coronary artery disease (CAD)

- Symptoms of CAD on systems review

- Cardiac arrhythmias

Any of the following therapies prior to pre-registration:

- Chemotherapy =< 4 weeks

- Immunotherapy =< 4 weeks

- Biologic therapy =< 4 weeks; Note exception: prior viral and/or gene therapy are
exclusion criteria

- Radiotherapy =< 4 weeks Failure to fully recover from acute, reversible effects of
prior anti-cancer therapy regardless of interval since last treatment; NOTE: patients
must have fully recovered from all acute, reversible toxicities (defined as Common
Terminology Criteria for Adverse Events [CTCAE] 4.0 =< grade 1) associated with
previous treatment

Any of the following because this study involves an investigational agent whose genotoxic,
mutagenic and teratogenic effects on the developing fetus and newborn are unknown:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate

- Any ancillary therapy considered investigational (utilized for a non-Food and
Drug Administration [FDA] approved indication and in the context of a research
investigation) or any other treatment specifically for treating the current

- Immunocompromised patients, including patients known to be HIV positive

- Other active malignancy =< 5 years prior to pre-registration; EXCEPTIONS:
non-melanotic skin cancer or carcinoma-in-situ of the cervix

- History of organ transplantation

- Known hepatitis B or C

- Treatment with oral/systemic corticosteroids; NOTE: with the exception of
topical or inhaled steroids

- Exposure to household contacts =<15 months old or household contact with a
person with known immunodeficiency

- Allergy to measles vaccine or history of severe reaction to prior measles

- Allergy to iodine; NOTE: this does not include reactions to intravenous contrast

- History of tuberculosis or purified protein derivative (PPD) skin test

- Prior pleurodesis or preexisting pleural catheter >= 4 weeks prior to

- Inability or unwillingness to have pleural catheter placed

- Requiring ongoing blood product support at time of pre-registration

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Adverse event (AE) profile

Outcome Description:

The number and severity of toxicity incidents will indicate the level of tolerance for MV-NIS in the therapy of MPM. Non-hematologic toxicities will be evaluated via the CTCAE v4.0 standard toxicity grading. Hematologic toxicity measures such as anemia, neutropenia and thrombocytopenia will be assessed using continuous variables as the outcome measures (nadir and percent change from baseline values) as well as categorization via CTCAE v4.0 standard toxicity grading. Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

Outcome Time Frame:

90 Days

Safety Issue:


Principal Investigator

Tobias Peikert

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

Related Keywords:

  • Recurrent Malignant Mesothelioma
  • Stage IA Malignant Mesothelioma
  • Stage IB Malignant Mesothelioma
  • Stage II Malignant Mesothelioma
  • Stage III Malignant Mesothelioma
  • Stage IV Malignant Mesothelioma
  • Measles
  • Mesothelioma



Mayo Clinic Rochester, Minnesota  55905