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CompletedNCT02316171CANONUpdated Jul 27, 2022Results posted

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

A Phase 1 interventional study of CVA21 and Mitomycin C in Non-muscle Invasive Bladder Cancer, sponsored by Viralytics. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-07-27.

Sponsored by Viralytics · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
16
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Non-muscle Invasive Bladder Cancer

Keywords

  • Coxsackievirus A21
  • bladder cancer
  • CVA21
  • CAVATAK
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • Experimental
    CVA21

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

    Biological: CVA21

  • Experimental
    CVA21/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.

    Biological: CVA21 · Drug: Mitomycin C

Interventions

  • BiologicalCVA21

    CAVATAK is a purified preparation of CVA21

    Also known as: CAVATAK, Coxsackievirus A21

  • DrugMitomycin C

    Chemotherapy

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 30 days from last dose

06

Results

Posted Jun 17, 2019
Limitations and caveats
Small number of subjects with limited follow-up; study not designed to give any indication of efficacy. The analysis for each dose escalation cohort for CVA21 only was pooled as the numbers were so small. This resulted in an analysis showing 2 arms.

Participant flow

9 patients were enrolled into VLA012A and 6 patients into VLA012B and data presented for these 15 patients. One patient was enrolled, but not treated due to difficulties in placing the urinary catheter.

Participant flow — Overall Study
MilestoneA1 - CVA21 1x10^8 TCID50CVA21/Mitomycin CA2 - CVA21 3x10^8 TCID50.A3 - CVA21 3x10^8 TCID50 x2
Started4633
Completed3633
Not completed1000
Withdrew: Difficulties with urinary catheter1000

Outcome measures

PrimaryIncidence 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.

Time frame:
30 days from last dose
Reported as:
Count of participants · Participants
Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
ParticipantsCVA21CVA21/Mitomycin C
Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.96

Adverse events

Collected over 30 days. The analysis for each dose escalation cohort for CVA21 only was pooled as the numbers were so small. This resulted in an analysis showing 2 arms.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CVA210/9 (0%)1/9 (11.1%)9/9 (100%)
CVA21/Mitomycin C0/6 (0%)0/6 (0%)6/6 (100%)
Most frequent serious events
Most frequent serious events
EventCVA21CVA21/Mitomycin C
E. Coli urinary tract infectionInfections and infestations1/90/6
Most frequent other events
Showing 10 of 41
Most frequent other events
EventCVA21CVA21/Mitomycin C
HematuriaRenal and urinary disorders5/94/6
DysuriaRenal and urinary disorders5/91/6
PollakiuriaRenal and urinary disorders3/91/6
HyperglycaemiaMetabolism and nutrition disorders3/91/6
Urinary tract infection enterococcalInfections and infestations2/91/6
Escherichia urinary tract infectionInfections and infestations2/90/6
Blood urea increasedInvestigations2/90/6
Blood uric acid increasedInvestigations2/90/6
FatigueGeneral disorders2/90/6
Decreased appetiteMetabolism and nutrition disorders2/90/6

Baseline characteristics

Received at least one dose of treatment.

Age, Continuous
Age, Continuous(years)CVA21CVA21/MitomycinCTotal
Mean67 ± 11.662.7 ± 8.365 ± 9.4
Sex: Female, Male
Sex: Female, Male(Participants)CVA21CVA21/MitomycinCTotal
Female213
Male7512
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)CVA21CVA21/MitomycinCTotal
Hispanic or Latino000
Not Hispanic or Latino9615
Unknown or Not Reported000
07

Study locations

1 site
  • University of Surrey
    Guildford, United Kingdom
08

References and documents

Publications

  • 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. PubMed 31273010 ↗
09

Registry details

Key details

Study ID
NCT02316171
Lead sponsor
Viralytics
Responsible party
Sponsor
First posted
Dec 12, 2014
Start date
Jan 16, 2015
Primary completion
Mar 14, 2016
Completion
Mar 14, 2016
Results posted
Jun 17, 2019
Last update
Jul 27, 2022

Study contacts

Hardev Pandha
principal investigator · Royal Surrey County Hospital NHS Foundation Trust

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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