Study of Intratumoral REOLYSIN® in Combination With Gemcitabine and Cisplatin as Neoadjuvant Therapy in Muscle-invasive Transitional Cell Carcinoma of the Bladder

Inclusion Criteria:

• Histologically and clinically confirmed muscle-invasive bladder cancer (T2-4) with or without pelvic lymph nodes involvement (N1-2) in Stage III and IV (M0).
• ECOG performance status ≤2.
• Adequate liver function with a bilirubin within normal limits. Transaminases up to 3 x ULN (Grade 1) and alkaline phosphatase may be up to 2.5 x ULN (Grade 1).
• Adequate bone marrow function, as defined by neutrophils count of ≥1,500/mm3, and platelet count ≥100,000/ mm3.
• Adequate renal function (serum creatinine ≤1.5 times the ULN).
• Negative pregnancy test and reliable and appropriate contraceptive method during the study for a woman of childbearing potential. All female patients of childbearing age and all male patients with partners of childbearing age should use a reliable method of contraception, such as the barrier method, throughout the study and for 60 days after last treatment.
• Informed of the investigational nature of this study and must sign a written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

• Received any prior therapy for invasive bladder cancer including surgery, radiation therapy, chemotherapy or any other systemic anti-cancer therapy (prior intravesical therapy for non-invasive bladder cancer is acceptable including intravesical BCG and/or mitomycin and interferon).
• Evidence of lymph nodes or other metastatic disease beyond the pelvis (N3 and/or M1).
• Pre-existing immunosuppressive or connective tissue disorders that require immune suppressive drugs.
• History of HIV or active hepatitis.
• Any serious concurrent illness including; but not limited to, unstable angina pectoris, uncompensated congestive cardiac failure; myocardial infarct in the previous 6 months; cardiac arrhythmias or psychiatric illness that would limit compliance with study requirements.
• Pregnant or lactating.
• A history of hypersensitivity to gemcitabine and cisplatin or any component of the formulation.
• A prior malignancy, other than non-melanoma skin cancer, unless they have completed therapy at least 5 years prior to start of study and have no evidence of recurrent or residual disease.
• Unwilling or unable to sign informed consent document.
• In social situations that would limit compliance with study requirements.