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

Viralytics

Status and phase: Completed; Phase 1

Conditions: Non-muscle Invasive Bladder Cancer

Treatments: Drug: Mitomycin C; Biological: CVA21

Study type: Interventional

Funder types: Industry

Identifiers

NCT02316171

2014-003938-81 (EudraCT Number)

VLA-012 (Other Identifier)

V937-008

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

CVA21

Experimental group

Description:

CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.

Treatment:

Biological: CVA21

CVA21/Mitomycin C

Experimental group

Description:

Mitomycin C (MMC) was administered at 10 mg by intravesical instillation on Day 1. Four hours after instillation of MMC, CVA21 was administered by intravesical instillation of one of 2 ascending dose levels or schedules. Subjects received a second instillation of CVA21 alone on Day 2 without pretreatment with MMC.

Treatment:

Drug: Mitomycin C

Biological: CVA21