Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer

NCT ID: NCT02070120

Last Updated: 2020-03-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

82 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2020-09-30

Brief Summary

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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

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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.

Conditions

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Bladder Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemoresection

4 once weekly outpatient intravesical instillations 40mg Mitomycin C

Group Type EXPERIMENTAL

Mitomycin C

Intervention Type DRUG

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

Surgical Management

Surgical management according to local practice

Group Type OTHER

Surgical Management

Intervention Type PROCEDURE

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

Interventions

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Mitomycin C

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

Intervention Type DRUG

Surgical Management

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

Intervention Type PROCEDURE

Other Intervention Names

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MMC

Eligibility Criteria

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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
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hugh Mostafid

Role: PRINCIPAL_INVESTIGATOR

Royal Surrey County Hospital NHS Foundation Trust

Locations

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Withington Hospital

Manchester, , United Kingdom

Site Status

Wythenshawe Hospital

Manchester, , United Kingdom

Site Status

Worcester Royal Hospital

Worcester, Worcestershire, United Kingdom

Site Status

St James's University Hospital

Leeds, Yorkshire, United Kingdom

Site Status

University College Hospital

London, , United Kingdom

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Macclesfield District General Hospital

Macclesfield, Cheshire, United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, Cleveland, United Kingdom

Site Status

West Cumberland Hospital

Whitehaven, Cumbria, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, Devon, United Kingdom

Site Status

Derriford Hospital

Plymouth, Devon, United Kingdom

Site Status

Royal Bournemouth Hospital

Bournemouth, Dorset, United Kingdom

Site Status

Dorset County Hospital

Dorchester, Dorset, United Kingdom

Site Status

Cumberland Infirmary

Carlisle, England, United Kingdom

Site Status

Broomfield Hospital

Chelmsford, Essex, United Kingdom

Site Status

Princess Alexandra Hospital

Harlow, Essex, United Kingdom

Site Status

Cheltenham General Hospital

Cheltenham, Gloucestershire, United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, Gloucestershire, United Kingdom

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Royal Oldham Hospital

Manchester, Greater Manchester, United Kingdom

Site Status

Basingstoke and North Hampshire Hospital

Basingstoke, Hampshire, United Kingdom

Site Status

Southampton General Hospital

Southampton, Hampshire, United Kingdom

Site Status

Hereford County Hospital

Hereford, Herefordshire, United Kingdom

Site Status

Darent Valley Hospital

Dartford, Kent, United Kingdom

Site Status

Medway Maritime Hospital

Gillingham, Kent, United Kingdom

Site Status

Royal Preston Hospital

Preston, Lancashire, United Kingdom

Site Status

Leicester General Hospital

Leicester, Leicestershire, United Kingdom

Site Status

Northwick Park Hospital

Harrow, Middlesex, United Kingdom

Site Status

Churchill Hospital

Headington, Oxfordshire, United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, South Yorkshire, United Kingdom

Site Status

Ipswich Hospital

Ipswich, Suffolk, United Kingdom

Site Status

Croydon University Hospital

Croydon, Surrey, United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, Surrey, United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, Tyne and Wear, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, West Midlands, United Kingdom

Site Status

St Richard's Hospital

Chichester, West Sussex, United Kingdom

Site Status

Worthing Hospital

Worthing, West Sussex, United Kingdom

Site Status

Pinderfields General Hospital

Wakefield, West Yorkshire, United Kingdom

Site Status

Kidderminster Hospital

Kidderminster, Worcestershire, United Kingdom

Site Status

Alexandra Hospital

Redditch, Worcestershire, United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type RESULT
PMID: 32124514 (View on PubMed)

Other Identifiers

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2013-005095-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ICR-CTSU/2013/10041

Identifier Type: -

Identifier Source: org_study_id

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