Clinical trial NCT02070120: Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer
Official title: CALIBER - A Phase II Randomised Feasibility Study of Chemoresection and Surgical Management in Low Risk Non Muscle Invasive Bladder Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: Nonmuscle invasive bladder cancer (NMIBC)
Mitomycin C
Chemoresection
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2014-02-25
Enrollment: 82
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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
* 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

Primary outcomes:
measure: Complete response rate with chemoresection
timeFrame: 3 months
Secondary outcomes:
measure: Treatment compliance in chemoresection group
timeFrame: Duration of treatment (3 weeks)
measure: Salvage surgery rates
timeFrame: 3 years
measure: Progression-free survival
timeFrame: 3 years
measure: Toxicity (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4 and Clavien Dindo grade (in surgical group))
timeFrame: up to 12 months
measure: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Superficial Bladder Cancer (BLS24) questionnaire
timeFrame: up to 12 months
measure: Health service utilisation
timeFrame: up to 12 months
measure: Recurrence free interval
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Macclesfield
country: United Kingdom
facility: Macclesfield District General Hospital
state: Cheshire
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: Cleveland
city: Whitehaven
country: United Kingdom
facility: West Cumberland Hospital
state: Cumbria
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: Devon
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: Dorset
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: Dorset
city: Carlisle
country: United Kingdom
facility: Cumberland Infirmary
state: England
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: Essex
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital
state: Essex
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
state: Gloucestershire
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: Gloucestershire
city: Manchester
country: United Kingdom
facility: Royal Oldham Hospital
state: Greater Manchester
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire Hospital
state: Hampshire
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Hereford
country: United Kingdom
facility: Hereford County Hospital
state: Herefordshire
city: Dartford
country: United Kingdom
facility: Darent Valley Hospital
state: Kent
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
state: Kent
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
state: Lancashire
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
state: Leicestershire
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: Middlesex
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: South Yorkshire
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: Suffolk
city: Croydon
country: United Kingdom
facility: Croydon University Hospital
state: Surrey
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
state: Tyne And Wear
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: West Midlands
city: Chichester
country: United Kingdom
facility: St Richard's Hospital
state: West Sussex
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: West Sussex
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
state: West Yorkshire
city: Kidderminster
country: United Kingdom
facility: Kidderminster Hospital
state: Worcestershire
city: Redditch
country: United Kingdom
facility: Alexandra Hospital
state: Worcestershire
city: Worcester
country: United Kingdom
facility: Worcester Royal Hospital
state: Worcestershire
city: Leeds
country: United Kingdom
facility: St James's University Hospital
state: Yorkshire
city: London
country: United Kingdom
facility: University College Hospital
city: Manchester
country: United Kingdom
facility: Withington Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
Study officials:
affiliation: Royal Surrey County Hospital NHS Foundation Trust
name: Hugh Mostafid
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mostafid AH, Porta N, Cresswell J, Griffiths TRL, Kelly JD, Penegar SR, Davenport K, McGrath JS, Campain N, Cooke P, Masood S, Knowles MA, Feber A, Knight A, Catto JWF, Lewis R, Hall E. CALIBER: a phase II randomized feasibility trial of chemoablation with mitomycin-C vs surgical management in low-risk non-muscle-invasive bladder cancer. BJU Int. 2020 Jun;125(6):817-826. doi: 10.1111/bju.15038. Epub 2020 Apr 3.