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Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer (CALIBER)

Primary Purpose

Bladder Cancer

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Mitomycin C
Surgical Management
Sponsored by
Institute of Cancer Research, United Kingdom
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer focused on measuring Nonmuscle invasive bladder cancer (NMIBC), Mitomycin C, Chemoresection

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Macclesfield District General Hospital
  • James Cook University Hospital
  • West Cumberland Hospital
  • Royal Devon and Exeter Hospital
  • Derriford Hospital
  • Royal Bournemouth Hospital
  • Dorset County Hospital
  • Cumberland Infirmary
  • Broomfield Hospital
  • Princess Alexandra Hospital
  • Cheltenham General Hospital
  • Gloucestershire Royal Hospital
  • Royal Oldham Hospital
  • Basingstoke and North Hampshire Hospital
  • Southampton General Hospital
  • Hereford County Hospital
  • Darent Valley Hospital
  • Medway Maritime Hospital
  • Royal Preston Hospital
  • Leicester General Hospital
  • Northwick Park Hospital
  • Churchill Hospital
  • Royal Hallamshire Hospital
  • Ipswich Hospital
  • Croydon University Hospital
  • Royal Surrey County Hospital
  • Freeman Hospital
  • New Cross Hospital
  • St Richard's Hospital
  • Worthing Hospital
  • Pinderfields General Hospital
  • Kidderminster Hospital
  • Alexandra Hospital
  • Worcester Royal Hospital
  • St James's University Hospital
  • University College Hospital
  • Withington Hospital
  • Wythenshawe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Chemoresection

Surgical Management

Arm Description

4 once weekly outpatient intravesical instillations 40mg Mitomycin C

Surgical management according to local practice

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Salvage surgery rates
Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups
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.
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
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.
Health service utilisation
Assessed using prospective data collection of health resource usage.
Recurrence free interval
Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months

Full Information

First Posted
February 19, 2014
Last Updated
March 17, 2020
Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
National Institute for Health Research, United Kingdom
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1. Study Identification

Unique Protocol Identification Number
NCT02070120
Brief Title
Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer
Acronym
CALIBER
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
October 2014 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
September 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Cancer Research, United Kingdom
Collaborators
National Institute for Health Research, United Kingdom

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer
Keywords
Nonmuscle invasive bladder cancer (NMIBC), Mitomycin C, Chemoresection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemoresection
Arm Type
Experimental
Arm Description
4 once weekly outpatient intravesical instillations 40mg Mitomycin C
Arm Title
Surgical Management
Arm Type
Other
Arm Description
Surgical management according to local practice
Intervention Type
Drug
Intervention Name(s)
Mitomycin C
Other Intervention Name(s)
MMC
Intervention Description
Patients assigned to the chemoresection group will receive 4 once weekly intravesical instillations of 40mg MMC as outpatients.
Intervention Type
Procedure
Intervention Name(s)
Surgical Management
Intervention Description
Patients in this group should be treated according to local practice. Surgical interventions may include transurethral resection (TUR) or ablation.
Primary Outcome Measure Information:
Title
Complete response rate with chemoresection
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Treatment compliance in chemoresection group
Description
Patients who receive 4 MMC instillations with no more than 14 days between each instillation will be described as fully compliant.
Time Frame
Duration of treatment (3 weeks)
Title
Salvage surgery rates
Description
Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups
Time Frame
3 years
Title
Progression-free survival
Description
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.
Time Frame
3 years
Title
Toxicity (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4 and Clavien Dindo grade (in surgical group))
Description
Measuring side effects of both treatments using clinician reported toxicity scales
Time Frame
up to 12 months
Title
European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Superficial Bladder Cancer (BLS24) questionnaire
Description
Assessing side effects and impact of both treatments on patient reported quality of life.
Time Frame
up to 12 months
Title
Health service utilisation
Description
Assessed using prospective data collection of health resource usage.
Time Frame
up to 12 months
Title
Recurrence free interval
Description
Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months
Time Frame
up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hugh Mostafid
Organizational Affiliation
Royal Surrey County Hospital NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Macclesfield District General Hospital
City
Macclesfield
State/Province
Cheshire
ZIP/Postal Code
SK10 3BL
Country
United Kingdom
Facility Name
James Cook University Hospital
City
Middlesbrough
State/Province
Cleveland
ZIP/Postal Code
TS4 3BW
Country
United Kingdom
Facility Name
West Cumberland Hospital
City
Whitehaven
State/Province
Cumbria
ZIP/Postal Code
CA28 8JG
Country
United Kingdom
Facility Name
Royal Devon and Exeter Hospital
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX2 5DW
Country
United Kingdom
Facility Name
Derriford Hospital
City
Plymouth
State/Province
Devon
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Facility Name
Royal Bournemouth Hospital
City
Bournemouth
State/Province
Dorset
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Dorset County Hospital
City
Dorchester
State/Province
Dorset
ZIP/Postal Code
DT1 2JY
Country
United Kingdom
Facility Name
Cumberland Infirmary
City
Carlisle
State/Province
England
ZIP/Postal Code
CA2 7HY
Country
United Kingdom
Facility Name
Broomfield Hospital
City
Chelmsford
State/Province
Essex
ZIP/Postal Code
CM1 5ET
Country
United Kingdom
Facility Name
Princess Alexandra Hospital
City
Harlow
State/Province
Essex
ZIP/Postal Code
CM20 1QX
Country
United Kingdom
Facility Name
Cheltenham General Hospital
City
Cheltenham
State/Province
Gloucestershire
ZIP/Postal Code
GL53 7AN
Country
United Kingdom
Facility Name
Gloucestershire Royal Hospital
City
Gloucester
State/Province
Gloucestershire
ZIP/Postal Code
GL1 3NN
Country
United Kingdom
Facility Name
Royal Oldham Hospital
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
OL1 2JH
Country
United Kingdom
Facility Name
Basingstoke and North Hampshire Hospital
City
Basingstoke
State/Province
Hampshire
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
State/Province
Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Hereford County Hospital
City
Hereford
State/Province
Herefordshire
ZIP/Postal Code
HR1 2ER
Country
United Kingdom
Facility Name
Darent Valley Hospital
City
Dartford
State/Province
Kent
ZIP/Postal Code
DA2 8DA
Country
United Kingdom
Facility Name
Medway Maritime Hospital
City
Gillingham
State/Province
Kent
ZIP/Postal Code
ME7 5NY
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
State/Province
Lancashire
ZIP/Postal Code
PR2 9HT
Country
United Kingdom
Facility Name
Leicester General Hospital
City
Leicester
State/Province
Leicestershire
ZIP/Postal Code
LE5 4PW
Country
United Kingdom
Facility Name
Northwick Park Hospital
City
Harrow
State/Province
Middlesex
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Churchill Hospital
City
Headington
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Facility Name
Ipswich Hospital
City
Ipswich
State/Province
Suffolk
ZIP/Postal Code
IP4 5PD
Country
United Kingdom
Facility Name
Croydon University Hospital
City
Croydon
State/Province
Surrey
ZIP/Postal Code
CR7 7YE
Country
United Kingdom
Facility Name
Royal Surrey County Hospital
City
Guildford
State/Province
Surrey
ZIP/Postal Code
GU2 7XX
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle upon Tyne
State/Province
Tyne And Wear
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
Facility Name
New Cross Hospital
City
Wolverhampton
State/Province
West Midlands
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
Facility Name
St Richard's Hospital
City
Chichester
State/Province
West Sussex
ZIP/Postal Code
PO19 6SE
Country
United Kingdom
Facility Name
Worthing Hospital
City
Worthing
State/Province
West Sussex
ZIP/Postal Code
BN11 2DH
Country
United Kingdom
Facility Name
Pinderfields General Hospital
City
Wakefield
State/Province
West Yorkshire
ZIP/Postal Code
WF1 4DG
Country
United Kingdom
Facility Name
Kidderminster Hospital
City
Kidderminster
State/Province
Worcestershire
ZIP/Postal Code
DY11 6RJ
Country
United Kingdom
Facility Name
Alexandra Hospital
City
Redditch
State/Province
Worcestershire
ZIP/Postal Code
B98 7UB
Country
United Kingdom
Facility Name
Worcester Royal Hospital
City
Worcester
State/Province
Worcestershire
ZIP/Postal Code
WR5 1DD
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
State/Province
Yorkshire
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
University College Hospital
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Withington Hospital
City
Manchester
ZIP/Postal Code
M20 2LR
Country
United Kingdom
Facility Name
Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32124514
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.
Results Reference
result

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Investigating Bladder Chemotherapy Instead of Surgery for Low Risk Bladder Cancer

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