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

NCT ID: NCT02316171

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-16
• Study Completion Date: 2016-03-14

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.

Conditions

Non-muscle Invasive Bladder Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CVA21

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

Group Type: EXPERIMENTAL

CVA21

Intervention Type: BIOLOGICAL

CAVATAK is a purified preparation of CVA21

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.

Group Type: EXPERIMENTAL

CVA21

Intervention Type: BIOLOGICAL

CAVATAK is a purified preparation of CVA21

Mitomycin C

Intervention Type: DRUG

Chemotherapy

Interventions

CVA21

CAVATAK is a purified preparation of CVA21

Intervention Type: BIOLOGICAL

Mitomycin C

Chemotherapy

Intervention Type: DRUG

Other Intervention Names

CAVATAK, Coxsackievirus A21

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Viralytics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hardev Pandha

Role: PRINCIPAL_INVESTIGATOR

Royal Surrey County Hospital NHS Foundation Trust

Locations

University of Surrey

Guildford, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 31273010 (View on PubMed)

Other Identifiers

VLA-012

Identifier Type: OTHER

Identifier Source: secondary_id

2014-003938-81

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

V937-008

Identifier Type: -

Identifier Source: org_study_id