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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Non-muscle Invasive Bladder Cancer

Intervention / Treatment
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* Biological: CVA21
* Drug: Mitomycin C


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVA21<br>CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules. | Biological: CVA21<br>* CAVATAK is a purified preparation of CVA21<br>* Other names: CAVATAK, Coxsackievirus A21;|
| Experimental: CVA21/Mitomycin C<br>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. | Biological: CVA21<br>* CAVATAK is a purified preparation of CVA21<br>* Other names: CAVATAK, Coxsackievirus A21;Drug: Mitomycin C<br>* Chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose-limiting Toxicities Treatment-related Adverse Events. | Number of Participants with Treatment-emergent adverse events. The events for each cohort of dose of CVA21 only are pooled for the analysis. | 30 days from last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coxsackievirus A21, bladder cancer, CVA21, CAVATAK