CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)

A Phase 1 Study to Evaluate the Safety and Clinical Activity of Intravesicular CAVATAK (Coxsackievirus A21, CVA21) Alone and in Sequential Combination With Low Dose Mitomycin C in Patients With Non-Muscle Invasive Bladder Cancer (VLA-012 CANON)

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