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

A Phase II Study of Intratumoral Injection of Interleukin-12 Plasmid and in Vivo Electroporation in Patients With Merkel Cell Carcinoma

This phase II trial studies the effectiveness of ImmunoPulse IL-12® in treating patients with Merkel cell cancer. ImmunoPulse IL-12® is the combination of intratumoral interleukin-12 gene (also known as tavokinogene telseplasmid [tavo]) and in vivo electroporation-mediated plasmid deoxyribonucleic acid [DNA] vaccine therapy (tavo-EP) administered using the OncoSec Medical System (OMS). Placing the gene for interleukin-12 into Merkel cells may help the mount an effective anti-tumor immune response to kill tumor cells.

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