Back to resultsCAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON) (CANON)
Primary Purpose
Non-muscle Invasive Bladder Cancer
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
CVA21
Mitomycin C
Sponsored by
About this trial
This is an interventional treatment trial for Non-muscle Invasive Bladder Cancer focused on measuring Coxsackievirus A21, bladder cancer, CVA21, CAVATAK
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
Sites / Locations
- University of Surrey
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
CVA21
CVA21/Mitomycin C
Arm Description
CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02316171
Brief Title
CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)
Acronym
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
January 16, 2015 (Actual)
Primary Completion Date
March 14, 2016 (Actual)
Study Completion Date
March 14, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Viralytics
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-muscle Invasive Bladder Cancer
Keywords
Coxsackievirus A21, bladder cancer, CVA21, CAVATAK
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CVA21
Arm Type
Experimental
Arm Description
CVA21 was administered by intravesical instillation at one of three (3) ascending dose levels or schedules.
Arm Title
CVA21/Mitomycin C
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CVA21
Other Intervention Name(s)
CAVATAK, Coxsackievirus A21
Intervention Description
CAVATAK is a purified preparation of CVA21
Intervention Type
Drug
Intervention Name(s)
Mitomycin C
Intervention Description
Chemotherapy
Primary Outcome Measure Information:
Title
Incidence of Dose-limiting Toxicities Treatment-related Adverse Events.
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hardev Pandha
Organizational Affiliation
Royal Surrey County Hospital NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Surrey
City
Guildford
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31273010
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.
Results Reference
result
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CAVATAK (CVA21) in Non-muscle Invasive Bladder Cancer (VLA-012 CANON)
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