CALIBER: Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Chemoresection 4 once weekly outpatient intravesical instillations 40mg Mitomycin C |
Drug: Mitomycin C
Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg MMC as outpatients.
Other Names:
|
| Other: Surgical Management Surgical management according to local practice |
Procedure: Surgical Management
Patients in this group should be treated according to local practice. Surgical interventions may include transurethral resection (TUR) or ablation.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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.
- Salvage surgery rates [3 years]
Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups
- 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.
- 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
- 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.
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
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Trial entry recurrence identified within 11.5 months of the date of the original diagnosis
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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
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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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Macclesfield District General Hospital | Macclesfield | Cheshire | United Kingdom | SK10 3BL |
| 2 | James Cook University Hospital | Middlesbrough | Cleveland | United Kingdom | TS4 3BW |
| 3 | West Cumberland Hospital | Whitehaven | Cumbria | United Kingdom | CA28 8JG |
| 4 | Royal Devon and Exeter Hospital | Exeter | Devon | United Kingdom | EX2 5DW |
| 5 | Derriford Hospital | Plymouth | Devon | United Kingdom | PL6 8DH |
| 6 | Royal Bournemouth Hospital | Bournemouth | Dorset | United Kingdom | BH7 7DW |
| 7 | Dorset County Hospital | Dorchester | Dorset | United Kingdom | DT1 2JY |
| 8 | Cumberland Infirmary | Carlisle | England | United Kingdom | CA2 7HY |
| 9 | Broomfield Hospital | Chelmsford | Essex | United Kingdom | CM1 5ET |
| 10 | Princess Alexandra Hospital | Harlow | Essex | United Kingdom | CM20 1QX |
| 11 | Cheltenham General Hospital | Cheltenham | Gloucestershire | United Kingdom | GL53 7AN |
| 12 | Gloucestershire Royal Hospital | Gloucester | Gloucestershire | United Kingdom | GL1 3NN |
| 13 | Royal Oldham Hospital | Manchester | Greater Manchester | United Kingdom | OL1 2JH |
| 14 | Basingstoke and North Hampshire Hospital | Basingstoke | Hampshire | United Kingdom | RG24 9NA |
| 15 | Southampton General Hospital | Southampton | Hampshire | United Kingdom | SO16 6YD |
| 16 | Hereford County Hospital | Hereford | Herefordshire | United Kingdom | HR1 2ER |
| 17 | Darent Valley Hospital | Dartford | Kent | United Kingdom | DA2 8DA |
| 18 | Medway Maritime Hospital | Gillingham | Kent | United Kingdom | ME7 5NY |
| 19 | Royal Preston Hospital | Preston | Lancashire | United Kingdom | PR2 9HT |
| 20 | Leicester General Hospital | Leicester | Leicestershire | United Kingdom | LE5 4PW |
| 21 | Northwick Park Hospital | Harrow | Middlesex | United Kingdom | HA1 3UJ |
| 22 | Churchill Hospital | Headington | Oxfordshire | United Kingdom | OX3 7LE |
| 23 | Royal Hallamshire Hospital | Sheffield | South Yorkshire | United Kingdom | S10 2JF |
| 24 | Ipswich Hospital | Ipswich | Suffolk | United Kingdom | IP4 5PD |
| 25 | Croydon University Hospital | Croydon | Surrey | United Kingdom | CR7 7YE |
| 26 | Royal Surrey County Hospital | Guildford | Surrey | United Kingdom | GU2 7XX |
| 27 | Freeman Hospital | Newcastle upon Tyne | Tyne And Wear | United Kingdom | NE7 7DN |
| 28 | New Cross Hospital | Wolverhampton | West Midlands | United Kingdom | WV10 0QP |
| 29 | St Richard's Hospital | Chichester | West Sussex | United Kingdom | PO19 6SE |
| 30 | Worthing Hospital | Worthing | West Sussex | United Kingdom | BN11 2DH |
| 31 | Pinderfields General Hospital | Wakefield | West Yorkshire | United Kingdom | WF1 4DG |
| 32 | Kidderminster Hospital | Kidderminster | Worcestershire | United Kingdom | DY11 6RJ |
| 33 | Alexandra Hospital | Redditch | Worcestershire | United Kingdom | B98 7UB |
| 34 | Worcester Royal Hospital | Worcester | Worcestershire | United Kingdom | WR5 1DD |
| 35 | St James's University Hospital | Leeds | Yorkshire | United Kingdom | LS9 7TF |
| 36 | University College Hospital | London | United Kingdom | NW1 2BU | |
| 37 | Withington Hospital | Manchester | United Kingdom | M20 2LR | |
| 38 | Wythenshawe Hospital | Manchester | United Kingdom | M23 9LT |
Sponsors and Collaborators
- Institute of Cancer Research, United Kingdom
- National Institute for Health Research, United Kingdom
Investigators
- Principal Investigator: Hugh Mostafid, Royal Surrey County Hospital NHS Foundation Trust
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ICR-CTSU/2013/10041
- 2013-005095-18