Phase I Trial of Intratumoral Administration of a NIS-Expressing Derivative Manufactured From a Genetically Engineered Strain of Measles Virus in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Location:

Rochester, Minn.

Trial status:
Open for Enrollment
Why is this study being done?

PRIMARY OBJECTIVES: I. To determine the maximally tolerated dose (MTD) of intratumoral administration of an Edmonston strain measles virus genetically engineered to express human thyroidal sodium-iodide symporter (NIS) (oncolytic measles virus encoding thyroidal sodium iodide symporter [MV-NIS]) in patients with recurrent/metastatic squamous cell head and neck cancer. SECONDARY OBJECTIVES: I. To determine the safety and toxicity of intratumoral administration of MV-NIS in patients with recurrent/metastatic squamous cell head and neck cancer. II. To assess in a preliminary fashion antitumor efficacy of this approach by following, radiographic response, and time to progression. TERTIARY 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. OUTLINE: This is a dose-escalation study. Patients receive oncolytic measles virus encoding thyroidal sodium iodide symporter intratumorally on day 1. After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 1 year and then every 6 months for 1 year.

Who is eligible to participate?

Inclusion Criteria: - Pathologically confirmed squamous cell carcinoma of the head and neck - Measurable disease - Head and neck cancer for which standard therapy is not curative - Patient may have more than one site of recurrence/metastatic disease but only one lesion will be injected that is >= 1 cm in size (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 ULN - Creatinine =< 1.0 mg/dL - 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 enrolling institution for follow-up - Willingness to provide biologic samples for correlative research purposes - Life expectancy >= 12 weeks - Must have anti-measles immunity as demonstrated by serum immunoglobulin G (IgG) anti-measles antibody levels of >= 20.0 EU/ml as determined by enzyme immunoassay (Diamedix, FL) - Cluster of differentiation (CD) 4 count >= 200/uL or >= 15% of peripheral blood lymphocytes 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) - Active infection =< 5 days prior to registration - History of tuberculosis or history of tuberculin 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 - Requiring blood product support - Central nervous system (CNS) metastases or seizure disorder - 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 - Willing to avoid household contacts =< 15 months old or household contact with known immunodeficiency 1 week after treatment - 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

Last updated:
3/10/2014
NCT ID:
NCT01846091
IRB Number:
11-007350