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

Phase 1

Completed

• Conditions: Non-muscle Invasive Bladder Cancer
• Interventions: Biological: CVA21; Drug: Mitomycin C

• Registration Number: NCT02316171
• Lead Sponsor: Viralytics

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2014-12-07
• Study First Submitted QC: 2014-12-09
• Study First Posted: 2014-12-12
• Study Start: 2015-01-16
• Primary Completion: 2016-03-14
• Study Completion: 2016-03-14
• Results First Submitted: 2017-11-02
• Results First Submitted QC: 2019-03-12
• Results First Posted: 2019-06-17
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-20
• Last Update Posted: 2022-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
CVA21	CVA21	CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.
CVA21/Mitomycin C	CVA21	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.
CVA21/Mitomycin C	Mitomycin C	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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

University of Surrey; 🇬🇧 Guildford, United Kingdom