Non-muscle Invasive Bladder Cancer
Conditions
Keywords
Coxsackievirus A21, bladder cancer, CVA21, CAVATAK
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.
Interventions
BIOLOGICALCVA21
CAVATAK is a purified preparation of CVA21
DRUGMitomycin C
Chemotherapy
Sponsors
Viralytics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-limiting Toxicities Treatment-related Adverse Events. | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| CVA21 CVA21 was administered by intravesical instillation of one of 3 ascending dose levels or schedules: | 9 |
| CVA21/MitomycinC 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 | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | difficulties with urinary catheter | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | CVA21 | CVA21/MitomycinC | Total |
|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 11.6 | 62.7 years STANDARD_DEVIATION 8.3 | 65 years STANDARD_DEVIATION 9.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 6 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 9 / 9 | 6 / 6 |
| serious Total, serious adverse events | 1 / 9 | 0 / 6 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CVA21 | Incidence of Dose-limiting Toxicities Treatment-related Adverse Events. | 9 Participants |
| CVA21/Mitomycin C | Incidence of Dose-limiting Toxicities Treatment-related Adverse Events. | 6 Participants |