Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer

Criteria for Evaluation:

Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.

Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.

Inclusion criteria

• Aged 18 years or older at the time of consent
• Able to give informed consent
• Subjects with high grade BCG-refractory or relapsed NMIBC including

• High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or
• Carcinoma in situ (CIS) only or
• CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment.

Relapse is defined as recurrence within 1 year after a complete response to BCG treatment

• Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
• Available for the whole duration of the study
• Life expectancy >2 years, in the opinion of the investigator
• ECOG status 2 or less
• Absence of upper tract urothelial carcinoma
• Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
• Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion.
• Adequate laboratory values.

• Hemoglobin ≥10 g/dL.
• WBC ≥4000/μL.
• ANC ≥2000/μL.
• Platelet count ≥100,000/μL.
• INR within institutional normal limits.
• aPTT within institutional normal limits.
• AST ≤1.5 x ULN.
• ALT ≤1.5 x ULN.
• Total bilirubin within institutional normal limits.
• Creatinine ≤1.5 x ULN.

Exclusion criteria

• Current or previous evidence of muscle invasive or metastatic disease
• Current systemic therapy for bladder cancer
• Current or prior pelvic external beam radiotherapy
• Prior treatment with adenovirus-based drugs
• Suspected hypersensitivity to interferon alpha
• Existing urinary tract infection or bacterial cystitis
• Clinically significant and unexplained elevated liver or renal function tests
• Women who are pregnant or lactating
• Severe cardiovascular disease
• History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
• Subjects who cannot hold instillation for 1 hour
• Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
• Intravesical therapy within 6 weeks of enrollment