Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer

Bladder Cancer Clinical Trial

— CALIBER  

Official title:

CALIBER - A Phase II Randomised Feasibility Study of Chemoresection and Surgical Management in Low Risk Non Muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02070120
• Other study ID #: ICR-CTSU/2013/10041
• Secondary ID: 2013-005095-18
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: September 2020

Study information

• Verified date: March 2020
• Source: Institute of Cancer Research, United Kingdom
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: September 2020
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

• 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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Mitomycin C
Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg MMC as outpatients.

Procedure:
• Surgical Management
Patients in this group should be treated according to local practice. Surgical interventions may include transurethral resection (TUR) or ablation.

Locations

Country	Name	City	State
United Kingdom	Basingstoke and North Hampshire Hospital	Basingstoke	Hampshire
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Cumberland Infirmary	Carlisle	England
United Kingdom	Broomfield Hospital	Chelmsford	Essex
United Kingdom	Cheltenham General Hospital	Cheltenham	Gloucestershire
United Kingdom	St Richard's Hospital	Chichester	West Sussex
United Kingdom	Croydon University Hospital	Croydon	Surrey
United Kingdom	Darent Valley Hospital	Dartford	Kent
United Kingdom	Dorset County Hospital	Dorchester	Dorset
United Kingdom	Royal Devon and Exeter Hospital	Exeter	Devon
United Kingdom	Medway Maritime Hospital	Gillingham	Kent
United Kingdom	Gloucestershire Royal Hospital	Gloucester	Gloucestershire
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Princess Alexandra Hospital	Harlow	Essex
United Kingdom	Northwick Park Hospital	Harrow	Middlesex
United Kingdom	Churchill Hospital	Headington	Oxfordshire
United Kingdom	Hereford County Hospital	Hereford	Herefordshire
United Kingdom	Ipswich Hospital	Ipswich	Suffolk
United Kingdom	Kidderminster Hospital	Kidderminster	Worcestershire
United Kingdom	St James's University Hospital	Leeds	Yorkshire
United Kingdom	Leicester General Hospital	Leicester	Leicestershire
United Kingdom	University College Hospital	London
United Kingdom	Macclesfield District General Hospital	Macclesfield	Cheshire
United Kingdom	Royal Oldham Hospital	Manchester	Greater Manchester
United Kingdom	Withington Hospital	Manchester
United Kingdom	Wythenshawe Hospital	Manchester
United Kingdom	James Cook University Hospital	Middlesbrough	Cleveland
United Kingdom	Freeman Hospital	Newcastle upon Tyne	Tyne And Wear
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Royal Preston Hospital	Preston	Lancashire
United Kingdom	Alexandra Hospital	Redditch	Worcestershire
United Kingdom	Royal Hallamshire Hospital	Sheffield	South Yorkshire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Pinderfields General Hospital	Wakefield	West Yorkshire
United Kingdom	West Cumberland Hospital	Whitehaven	Cumbria
United Kingdom	New Cross Hospital	Wolverhampton	West Midlands
United Kingdom	Worcester Royal Hospital	Worcester	Worcestershire
United Kingdom	Worthing Hospital	Worthing	West Sussex

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Cancer Research, United Kingdom	National Institute for Health Research, United Kingdom

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Mostafid AH, Porta N, Cresswell J, Griffiths T, Kelly JD, Penegar SR, Davenport K, McGrath JS, Campain N, Cooke P, Masood S, Knowles MA, Feber A, Knight A, Catto JW, Lewis R, Hall E. CALIBER - A phase II randomised feasibility trial of chemoablation with — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rate with chemoresection	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.	3 months
Secondary	Treatment compliance in chemoresection group	Patients who receive 4 MMC instillations with no more than 14 days between each instillation will be described as fully compliant.	Duration of treatment (3 weeks)
Secondary	Salvage surgery rates	Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups	3 years
Secondary	Progression-free survival	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.	3 years
Secondary	Toxicity (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4 and Clavien Dindo grade (in surgical group))	Measuring side effects of both treatments using clinician reported toxicity scales	up to 12 months
Secondary	European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Superficial Bladder Cancer (BLS24) questionnaire	Assessing side effects and impact of both treatments on patient reported quality of life.	up to 12 months
Secondary	Health service utilisation	Assessed using prospective data collection of health resource usage.	up to 12 months
Secondary	Recurrence free interval	Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months	up to 12 months