Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma

Inclusion Criteria:

• Diagnosis of histologically or cytologically documented, malignant pleural effusions (primary non-small-cell lung carcinoma, mesothelioma, and other histologies), who have free pleural space (partial or total) that permits the intrapleural drug instillation. This includes cytologically negative pleural effusion in conjunction with histologically proven malignancy involving the pleura.
• Age must be ≥ 18 years.
• All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade ≤ 1. Any surgery, where anesthesia was administered, must have occurred at least 14 days prior to study enrolment.
• Chemotherapy, radiotherapy or immunotherapy must have stopped more than 14 days prior to receiving study drug; however, small field palliative radiotherapy, TKI therapies and hormonal therapies are allowed.
• ECOG Zubrod ≤ 2.
• Required baseline laboratory data include:

Absolute neutrophil count (ANC) ≥ 1.5 × 109 [SI units 109/L],

• Platelets ≥ 100 ×109 [SI units 109/L],
• Hemoglobin ≥ 9.0 g/dL [SI units gm/L],
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN),
• Bilirubin ≤ 1.5 × ULN,
• AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases)
• Negative pregnancy test for females of childbearing potential.

Exclusion Criteria:

• Pregnant or breast-feeding women.
• Patients with fever or any active systemic infections, including known HIV, hepatitis B or C.
• Patients on immunosuppressive therapy or with immune system disorders, including autoimmune diseases.
• Concurrent steroid use of more than an equivalent of 20 mg/day prednisone (or equivalent).
• Prior splenectomy.
• Previous organ transplant.
• Patients with clinically significant dermatological disorders, e.g., eczema or psoriasis, as judged by the principal investigator, or any unhealed skin wounds or ulcers.
• Patients with symptomatic brain metastases requiring treatment.
• Clinically significant cardiac disease (New York Heart Association, Class III or IV).
• Dementia or altered mental status that would prohibit informed consent.
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the principal investigator, would make the patient inappropriate for this study.
• Known allergy to ovalbumin or other egg products.
• Prior gene therapy treatments or prior therapy with cytolytic virus of any type.
• Concurrent therapy with any other investigational anticancer agent.
• Concurrent antiviral agent active against vaccinia virus (e.g. cidofovir, vaccinia immunoglobulin) during the study.