IL-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Patients With Merkel Cell Cancer

PRIMARY OBJECTIVES:

I. To measure the effect of intratumoral injection of tavo followed by in vivo
electroporation (EP) (electroporation-mediated plasmid DNA vaccine therapy) on the local
expression of interleukin-12 (IL-12) in the tumor microenvironment in patients with Merkel
cell carcinoma (MCC).

SECONDARY OBJECTIVES:

I. To assess the safety of tavo-EP in MCC. II. To assess the clinical efficacy of this
treatment approach in MCC. III. To assess the immunologic changes resulting from this
treatment approach.

OUTLINE:

Patients receive tavo intratumorally (IT) and undergo electrical discharge via OMS around the
tumor site for electroporation-mediated plasmid DNA vaccine therapy on days 1, 5, and 8.
Patients with unresectable disease may receive a second course of treatment in 12 weeks.
Patients with localized disease proceed to definitive treatment as determined by the treating
physician starting 2-4 weeks after the first injection.

After completion of study treatment, patients are followed up at weeks 4-8 (for patients who
received definitive treatment) or 12 (for patients with unresectable disease) and then
annually for up to 5 years.

Inclusion Criteria:

- Patients must have biopsy-confirmed Merkel cell carcinoma

- Patients must have at least one injectable lesion, defined as an easily palpable
superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be
accurately localized, stabilized by palpation, and is superficial enough to enable
intratumoral injection and electroporation; the injectable lesion must not be in close
proximity to another tissue (e.g. nerve, bone) that could put patient safety at risk

- Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2

- Life expectancy of greater than three months

- Absolute neutrophil count > 1,000/uL

- Platelet count > 50,000/uL

- Creatinine =< 2.0 x upper limit of normal (ULN)

- Bilirubin =< 2.0 x ULN

- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 x ULN

- Patients must be willing, at the time of the entry to the study, to undergo the
pre-treatment fine needle aspiration (FNA) plus biopsy (if indicated) AND the
post-treatment FNA plus biopsy (or surgery) of at least one injected lesion (FNA is
essential to determine the primary endpoint of the study); NOTE: The pre-treatment
biopsy will be obtained from a superficial not-to-be-injected lesion; the
post-treatment biopsy of an injected lesion will be obviated if definitive surgical
resection is planned

- The effects of this treatment approach on the developing human fetus are unknown; for
this reason, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry and for the duration of study participation; should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her
treating physician immediately

- Patients must have the ability to understand and the willingness to sign a written
informed consent document

- Both men and women, and members of all races and ethnic groups are eligible for this
trial

Exclusion Criteria:

- Patients who have had prior chemotherapy, investigational therapy or a major surgical
procedure within 4 weeks or radiotherapy within 2 weeks prior to first day of
treatment

- Patients must not be receiving concurrently any other anti-cancer treatment (including
topical agents such as imiquimod) or investigational agents, which could potentially
interfere with the study treatment and/or study endpoints

- Patients with active untreated brain metastases will be excluded

- Pregnant or breast feeding women are excluded because effects of this treatment on the
fetus or passage through milk are unknown

- Patients with electronic pacemakers or defibrillators or those with a history of life
threatening cardiac arrhythmia or uncontrolled seizure disorder are excluded

- Use of any immunosuppressive treatments including corticosteroids, cyclosporine,
mycophenolate mofetil et cetera, within 4 weeks prior to Day 1 of treatment will not
be allowed; NOTE: Patients on topical or physiologic doses (for hormone-replacement
therapy) of corticosteroids will be allowed

- Patients, who are judged to be immunosuppressed due to uncontrolled human
immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent
hematological malignancy, or other comorbidities, will be excluded

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
serious infection, symptomatic congestive heart failure, unstable angina pectoris,
serious autoimmune conditions or psychiatric illness/social situations that would
limit compliance with study requirements

- Patients receiving concurrent therapeutic-dose anticoagulation will be excluded