Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Intrapleural Measles Virus Therapy in Patients With Malignant Pleural Mesothelioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01503177
First received: December 16, 2011
Last updated: September 12, 2014
Last verified: September 2014
  Purpose

This phase I clinical trial investigates the side effects and the best dose of local (intrapleural measles virus therapy in treating patients with malignant pleural mesothelioma (MPM). The investigators anticipate that the intrapleural of the vaccine strain measles virus will enable the virus to specifically infect and kill cancer cells and spare, without damaging normal cells. Furthermore, the investigators expect the measles virus to trigger an anti-tumor immune response which will result in additional destruction of the tumor by immune cells


Condition Intervention Phase
Recurrent Malignant Mesothelioma
Stage IA Malignant Mesothelioma
Stage IB Malignant Mesothelioma
Stage II Malignant Mesothelioma
Stage III Malignant Mesothelioma
Stage IV Malignant Mesothelioma
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Other: laboratory biomarker analysis
Procedure: single photon emission computed tomography
Procedure: computed tomography
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of Oncolytic Measles Virotherapy in Mesothelioma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Adverse event (AE) profile [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Describe the safety of the intrapleural administration of MV-NIS in patients with malignant pleural mesothelioma for all cycles out to 90 days. [ Time Frame: 90 Days ] [ Designated as safety issue: Yes ]
    The number and severity of adverse events (AE) over the course of up to 6 cycles of MV-NIS therapy will indicate the level of tolerance for MV-NIS in the therapy of MPM. AE will be evaluated similar to the primary outcome via the CTCAE v4.0 standard toxicity grading and frequency distributions and other descriptive measures will form the basis of the analysis of these variables.


Estimated Enrollment: 36
Study Start Date: November 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (viral therapy)
Patients receive MV-NIS intrapleurally on day 1. Treatment repeats every 28 days for up to 6 courses in absence of disease progression or unacceptable toxicity.
Biological: oncolytic measles virus encoding thyroidal sodium iodide symporter
Given intrapleurally
Other Name: MV-NIS
Other: laboratory biomarker analysis
Correlative studies
Procedure: single photon emission computed tomography
Correlative studies
Other Names:
  • SPECT imaging
  • tomography, emission computed, single photon
Procedure: computed tomography
Correlative studies
Other Name: tomography, computed

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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

TERTIARY OBJECTIVES:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PRE-REGISTRATION:

  • 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 pleural effusion with the ability to safely place an intrapleural catheter or have pre-existing intrapleural catheter
  • 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

REGISTRATION:

  • Anti-measles immunity as demonstrated by serum IgG anti-measles antibody levels of ≥ 1.1 EU/ml as determined by BioPlex Measles IgG multiplex flow 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:

PRE-REGISTRATION

  • 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 requirements
    • Symptomatic congestive heart failure New York Heart Association classification III or IV
    • 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 contraception

    • 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 malignancy
    • Immunocompromised patients, including patients known to be HIV positive
    • Other active malignancy =< 2 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 vaccination
    • Allergy to iodine; NOTE: this does not include reactions to intravenous contrast materials
    • History of tuberculosis or purified protein derivative (PPD) skin test positivity
    • Inability or unwillingness to have pleural catheter placed
    • Requiring ongoing blood product support at time of pre-registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01503177

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Tobias Peikert         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Tobias Peikert Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01503177     History of Changes
Other Study ID Numbers: MC1023, NCI-2011-03574
Study First Received: December 16, 2011
Last Updated: September 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Mesothelioma
Lung Neoplasms
Neoplasms, Mesothelial
Adenoma
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014