The study consisted of 2 sequential parts. Part A assessed the safety and tolerability of CAVATAK administered via intravesical instillation in patients with non-muscle invasive bladder cancer scheduled to undergo TUR. Part B assessed the safety and tolerability of CAVATAK administered in sequential combination with low dose Mitomycin C in the same patient population.

This was a Phase I, two-part, open-label, dose-escalation study designed to evaluate CVA21 alone and in sequential combination with low-dose mitomycin C in patients with non-muscle invasive bladder cancer (NMIBC) who were candidates for and were planning to undergo TUR for treatment of their disease. This gave a relatively homogeneous study population and facilitated collection of resected tumour tissue for histological, pharmacodynamics (PD) and pharmacokinetic (PK) analyses.

Inclusion Criteria:

• Clinical diagnosis of NMIBC based on cystoscopic appearance
• ECOG 0-2
• No intravesical therapy within 6 weeks of study entry
• No prior radiation to the pelvis
• ANC >1500/mm³; Hb >9.0 g/dL; Platelet >100000/mm³
• Serum creatinine ≤ 1.5 mg/dL
• Bilirubin within normal limits; AST ≤ 2.5x upper limit of normal (ULN); ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 2.5x ULN unless bone metastasis is present in the absence of liver metastasis
• INR < 1.2; aPPT = 0.8-1.2; PT = 0.9-1.8
• Candidate for TUR and planning to undergo TUR
• Negative pregnancy test within 7 days of treatment start
• Patients of child-bearing potential must agree to use an effective method of birth control

Exclusion Criteria:

• Prior local or systemic treatments for NMIBC
• Concurrent treatment with any chemotherapeutic agent
• Patients not deemed acceptable for general anaesthesia
• Women who are pregnant or lactating
• History of vesicoureteric reflux or an indwelling urinary stent
• Administration of an investigational agent within 3 months of study entry
• Active cardiac disease
• Known infection with HIV, hepatitis B or C
• Active uncontrolled infection

Received at least one dose of treatment.

30 days. The analysis for each dose escalation cohort for CVA21 only was pooled as the numbers were so small. This resulted in an analysis showing 2 arms.

No SUSARs were reported for the VLA-012 study.

Small number of subjects with limited follow-up; study not designed to give any indication of efficacy. The analysis for each dose escalation cohort for CVA21 only was pooled as the numbers were so small. This resulted in an analysis showing 2 arms.