Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer
- Registration Number
- NCT02070120
- Lead Sponsor
- Institute of Cancer Research, United Kingdom
- Brief Summary
Patients diagnosed with low risk non-muscle invasive bladder cancer (NMIBC) are at risk of frequent low grade recurrence, which usually necessitates surgical intervention under general anaesthetic. This multicentre study aims to establish the short term efficacy of chemoresection using chemotherapy within the bladder for the treatment of NMIBC.
Should the levels of complete response following chemoresection meet predefined criteria, a larger phase III trial would be developed to assess longer term disease related endpoints, with the aim of standardising management of recurrent low risk NMIBC and potentially removing the need for over a thousand patients each year to undergo surgery.
- Detailed Description
CALIBER is a two stage phase II, multicentre, randomised controlled trial (RCT). A control group has been included to provide prospective data about surgical management and outcomes and assess feasibility of recruitment to a randomised study.
Stage 1: 80 patients will be recruited with treatment allocated 2:1 by randomisation between chemoresection and surgical management.
Stage 2: If the stop/go activity criteria at the end of stage 1 indicate that recruitment should continue, 9 additional participants will be recruited, all of whom will receive chemoresection.
Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg Mitomycin C (MMC) as outpatients. This treatment will be delivered via catheter under local anaesthetic.
Patients assigned to the surgical management group will receive the standard surgical management in use at their hospital for treatment of recurrence which may include a single post-operative installation of 40mg MMC within 24 hours.
All participants will be followed up at 3 weeks from the start of treatment (ie at time of final MMC instillation for chemoresection group) and each will receive a cystoscopy three months from the end of treatment to assess response, in accordance with European Association of Urology (EAU) guidelines.
Subsequent cystoscopic follow up will take place 12 months after treatment if recurrence-free at 3 months and then annually.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 82
- Written informed consent
- NMIBC recurrence following original diagnosis of low risk NMIBC (defined as Ta G1 or Ta G2 (Ta low grade) with a risk of recurrence score of ≤6 using EORTC risk tables
- Histologically confirmed Transitional-cell carcinoma (TCC) at original diagnosis
- Aged 16 or over
- Satisfactory pre-treatment haematology values and serum creatinine < 1.5 x Upper Limit of Normal (ULN)
- Negative pregnancy test for women of child-bearing potential
- Any history of: grade 3/high grade or ≥T1 transitional cell carcinoma, concomitant carcinoma in situ, more than 7 tumours at one diagnosis or more than 1 recurrence per year since initial diagnosis or in the past five years, whichever is shorter
- Any history of histologically confirmed non-TCC bladder cancer
- Trial entry recurrence identified within 11.5 months of the date of the original diagnosis
- Any prior treatment of the trial entry recurrence (including biopsy)
- Previous MMC chemotherapy other than a single instillation at diagnostic surgery
- Known allergy to MMC
- Carcinoma involving the prostatic urethra or upper urinary tract (participants should have had imaging of the upper urinary tract within 2 years prior to randomisation)
- Known or suspected reduced bladder capacity (<100ml)
- Significant bleeding disorder
- Female patients who are breast-feeding or are of childbearing potential and unwilling or unable to use adequate non-hormonal contraception. Male patients should also use contraception if sexually active.
- Active or intractable urinary tract infection
- Urethral stricture or anything impeding the insertion of a catheter
- Large narrow neck diverticula
- Significant urinary incontinence
- Any other conditions that in the Principal Investigator's opinion would contraindicate protocol treatment
- Unable or unwilling to comply with study procedures or follow up schedule
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Surgical Management Surgical Management Surgical management according to local practice Chemoresection Mitomycin C 4 once weekly outpatient intravesical instillations 40mg Mitomycin C
- Primary Outcome Measures
Name Time Method Complete response rate with chemoresection 3 months Defined as an absence of any tumour following chemoresection and will be assessed visually at 3 month check cystoscopy by patients' urologists. A biopsy of the tumour bed would take place to confirm visual assessment of complete response.
- Secondary Outcome Measures
Name Time Method Treatment compliance in chemoresection group Duration of treatment (3 weeks) Patients who receive 4 MMC instillations with no more than 14 days between each instillation will be described as fully compliant.
Toxicity (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4 and Clavien Dindo grade (in surgical group)) up to 12 months Measuring side effects of both treatments using clinician reported toxicity scales
Progression-free survival 3 years Defined as time from randomisation to the first of muscle invasive bladder recurrence, recurrence in the pelvic nodes, distant metastatic recurrence or death from any cause.
Health service utilisation up to 12 months Assessed using prospective data collection of health resource usage.
Recurrence free interval up to 12 months Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months
Salvage surgery rates 3 years Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Superficial Bladder Cancer (BLS24) questionnaire up to 12 months Assessing side effects and impact of both treatments on patient reported quality of life.
Trial Locations
- Locations (38)
James Cook University Hospital
🇬🇧Middlesbrough, Cleveland, United Kingdom
Macclesfield District General Hospital
🇬🇧Macclesfield, Cheshire, United Kingdom
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
Dorset County Hospital
🇬🇧Dorchester, Dorset, United Kingdom
Cumberland Infirmary
🇬🇧Carlisle, England, United Kingdom
Darent Valley Hospital
🇬🇧Dartford, Kent, United Kingdom
Leicester General Hospital
🇬🇧Leicester, Leicestershire, United Kingdom
Northwick Park Hospital
🇬🇧Harrow, Middlesex, United Kingdom
Churchill Hospital
🇬🇧Headington, Oxfordshire, United Kingdom
Croydon University Hospital
🇬🇧Croydon, Surrey, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon Tyne, Tyne And Wear, United Kingdom
St Richard's Hospital
🇬🇧Chichester, West Sussex, United Kingdom
Worthing Hospital
🇬🇧Worthing, West Sussex, United Kingdom
Alexandra Hospital
🇬🇧Redditch, Worcestershire, United Kingdom
St James's University Hospital
🇬🇧Leeds, Yorkshire, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Withington Hospital
🇬🇧Manchester, United Kingdom
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Medway Maritime Hospital
🇬🇧Gillingham, Kent, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, Suffolk, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Princess Alexandra Hospital
🇬🇧Harlow, Essex, United Kingdom
Royal Oldham Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, West Midlands, United Kingdom
Pinderfields General Hospital
🇬🇧Wakefield, West Yorkshire, United Kingdom
Royal Bournemouth Hospital
🇬🇧Bournemouth, Dorset, United Kingdom
Hereford County Hospital
🇬🇧Hereford, Herefordshire, United Kingdom
West Cumberland Hospital
🇬🇧Whitehaven, Cumbria, United Kingdom
Royal Preston Hospital
🇬🇧Preston, Lancashire, United Kingdom
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, Hampshire, United Kingdom
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, Surrey, United Kingdom
Royal Devon and Exeter Hospital
🇬🇧Exeter, Devon, United Kingdom
Cheltenham General Hospital
🇬🇧Cheltenham, Gloucestershire, United Kingdom
Kidderminster Hospital
🇬🇧Kidderminster, Worcestershire, United Kingdom
Worcester Royal Hospital
🇬🇧Worcester, Worcestershire, United Kingdom
Gloucestershire Royal Hospital
🇬🇧Gloucester, Gloucestershire, United Kingdom