Non-muscle Invasive Bladder CancerPhase 1CANONNCT02316171

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

A Phase 1 study testing CVA21 and Mitomycin C in people with Non-muscle Invasive Bladder Cancer, run by Viralytics at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Non-muscle Invasive Bladder Cancer
What is being tested?: CVA21 and Mitomycin C
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited Kingdom
Study dates: 16 Jan 2015to 14 Mar 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

Show all 9Show fewer

Active cardiac disease
Known infection with HIV, hepatitis B or C
Active uncontrolled infection

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

University of Surrey
Guildford

Other trials in United Kingdom

About this study

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)

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.

Conditions: Non-muscle Invasive Bladder Cancer
Being tested: CVA21, Mitomycin C
Keywords: Coxsackievirus A21, bladder cancer, CVA21, CAVATAK
Medical subject headings: Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CVA21Biological
Also called CAVATAK, Coxsackievirus A21
CAVATAK is a purified preparation of CVA21
Mitomycin CDrug
Chemotherapy

Study groups in NCT02316171
Study group	Role	What they receive
CVA21	Experimental	CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules. Receives: Biological: CVA21
CVA21/Mitomycin C	Experimental	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. Receives: Biological: CVA21; Drug: Mitomycin C

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 30 days from last dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Jan 201514 Mar 2016

First posted12 Dec 2014 (estimated)
Study start16 Jan 2015
Primary completion14 Mar 2016
Study completion14 Mar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Non-muscle Invasive Bladder CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02316171
Sponsor's protocol ID: V937-008
Other IDs: VLA-012, 2014-003938-81, 2014
Acronym: CANON
Status last verified: Jul 2022
First submitted: 7 Dec 2014
Last updated: 27 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 27 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT02316171
Acronym / sponsor ID: CANON / V937-008
Conditions: Non-muscle Invasive Bladder Cancer
Keywords: Coxsackievirus A21, bladder cancer, CVA21, CAVATAK
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: ViralyticsIndustry (pharma, biotech, devices)
Study start: 16 Jan 2015 (actual)
Primary completion: 14 Mar 2016 (actual)
Study completion: 14 Mar 2016 (actual)
First posted: 12 Dec 2014 (estimated)
Results: Posted 17 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
CVA21	Experimental	Biological: CVA21CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.
CVA21/Mitomycin C	Experimental	Biological: CVA21, Drug: Mitomycin CMitomycin 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CVA21Also: CAVATAK, Coxsackievirus A21CAVATAK is a purified preparation of CVA21	Biological	CVA21, CVA21/Mitomycin C
Mitomycin CChemotherapy	Drug	CVA21/Mitomycin C

Primary outcome

Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
Time frame: 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.

Results and safety

Results posted to the registry on 17 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
A1 - CVA21 1x10^8 TCID50	4	3
CVA21/Mitomycin C	6	6
A2 - CVA21 3x10^8 TCID50.	3	3
A3 - CVA21 3x10^8 TCID50 x2	3	3

Primary outcome: Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.

Time frame: 30 days from last dose. Count of participants. Unit: Participants

Measure	CVA21 n = 9	CVA21/Mitomycin C n = 6
Value	9	6

Adverse events

Time frame: 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CVA21	1 of 9 (11.1%)	9 of 9 (100%)	0 of 9
CVA21/Mitomycin C	0 of 6 (0%)	6 of 6 (100%)	0 of 6

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 31273010Annels 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.
ViralyticsLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hardev Pandha principal investigator

Royal Surrey County Hospital NHS Foundation Trust

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CVA21 and Mitomycin C in people with Non-muscle Invasive Bladder Cancer, run by Viralytics at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-limiting Toxicities Treatment-related Adverse Events. (time frame: 30 days from last dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02316171, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2022.