Clinical trial NCT02316171: CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-muscle Invasive Bladder Cancer
Keywords: Coxsackievirus A21
bladder cancer
CVA21
CAVATAK
Lead sponsor: Viralytics
Sponsor class: INDUSTRY
First posted: 2014-12-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
timeFrame: 30 days from last dose
Secondary outcomes:
Other outcomes:
Locations:
city: Guildford
country: United Kingdom
facility: University of Surrey
Study officials:
affiliation: Royal Surrey County Hospital NHS Foundation Trust
name: Hardev Pandha
role: PRINCIPAL_INVESTIGATOR
References:
citation: Annels NE, Mansfield D, Arif M, Ballesteros-Merino C, Simpson GR, Denyer M, Sandhu SS, Melcher AA, Harrington KJ, Davies B, Au G, Grose M, Bagwan I, Fox B, Vile R, Mostafid H, Shafren D, Pandha HS. Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer. Clin Cancer Res. 2019 Oct 1;25(19):5818-5831. doi: 10.1158/1078-0432.CCR-18-4022. Epub 2019 Jul 4.