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

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ClinicalTrials.gov Identifier: NCT02070120
Recruitment Status : Active, not recruiting
First Posted : February 25, 2014
Last Update Posted : August 8, 2018
Sponsor:
Collaborator:
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
Institute of Cancer Research, United Kingdom

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
Bladder Cancer Drug: Mitomycin C Procedure: Surgical Management 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CALIBER - A Phase II Randomised Feasibility Study of Chemoresection and Surgical Management in Low Risk Non Muscle Invasive Bladder Cancer
Actual Study Start Date : October 2014
Actual Primary Completion Date : January 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

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 Name: MMC

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.




Primary Outcome Measures :
  1. Complete response rate with chemoresection [ Time Frame: 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 :
  1. Treatment compliance in chemoresection group [ Time Frame: 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.

  2. Salvage surgery rates [ Time Frame: 3 years ]
    Assessing trans-urethral resection and biopsy rates following initial treatment in both treatment groups

  3. Progression-free survival [ Time Frame: 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.

  4. Toxicity (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) V4 and Clavien Dindo grade (in surgical group)) [ Time Frame: up to 12 months ]
    Measuring side effects of both treatments using clinician reported toxicity scales

  5. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Superficial Bladder Cancer (BLS24) questionnaire [ Time Frame: up to 12 months ]
    Assessing side effects and impact of both treatments on patient reported quality of life.

  6. Health service utilisation [ Time Frame: up to 12 months ]
    Assessed using prospective data collection of health resource usage.

  7. Recurrence free interval [ Time Frame: up to 12 months ]
    Time from end of treatment to first relapse, in patients confirmed recurrence free at 3 months



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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02070120


Locations
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United Kingdom
Macclesfield District General Hospital
Macclesfield, Cheshire, United Kingdom, SK10 3BL
James Cook University Hospital
Middlesbrough, Cleveland, United Kingdom, TS4 3BW
West Cumberland Hospital
Whitehaven, Cumbria, United Kingdom, CA28 8JG
Royal Devon and Exeter Hospital
Exeter, Devon, United Kingdom, EX2 5DW
Derriford Hospital
Plymouth, Devon, United Kingdom, PL6 8DH
Royal Bournemouth Hospital
Bournemouth, Dorset, United Kingdom, BH7 7DW
Dorset County Hospital
Dorchester, Dorset, United Kingdom, DT1 2JY
Cumberland Infirmary
Carlisle, England, United Kingdom, CA2 7HY
Broomfield Hospital
Chelmsford, Essex, United Kingdom, CM1 5ET
Princess Alexandra Hospital
Harlow, Essex, United Kingdom, CM20 1QX
Cheltenham General Hospital
Cheltenham, Gloucestershire, United Kingdom, GL53 7AN
Gloucestershire Royal Hospital
Gloucester, Gloucestershire, United Kingdom, GL1 3NN
Royal Oldham Hospital
Manchester, Greater Manchester, United Kingdom, OL1 2JH
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, United Kingdom, RG24 9NA
Southampton General Hospital
Southampton, Hampshire, United Kingdom, SO16 6YD
Hereford County Hospital
Hereford, Herefordshire, United Kingdom, HR1 2ER
Darent Valley Hospital
Dartford, Kent, United Kingdom, DA2 8DA
Medway Maritime Hospital
Gillingham, Kent, United Kingdom, ME7 5NY
Royal Preston Hospital
Preston, Lancashire, United Kingdom, PR2 9HT
Leicester General Hospital
Leicester, Leicestershire, United Kingdom, LE5 4PW
Northwick Park Hospital
Harrow, Middlesex, United Kingdom, HA1 3UJ
Churchill Hospital
Headington, Oxfordshire, United Kingdom, OX3 7LE
Royal Hallamshire Hospital
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Ipswich Hospital
Ipswich, Suffolk, United Kingdom, IP4 5PD
Croydon University Hospital
Croydon, Surrey, United Kingdom, CR7 7YE
Royal Surrey County Hospital
Guildford, Surrey, United Kingdom, GU2 7XX
Freeman Hospital
Newcastle upon Tyne, Tyne And Wear, United Kingdom, NE7 7DN
New Cross Hospital
Wolverhampton, West Midlands, United Kingdom, WV10 0QP
St Richard's Hospital
Chichester, West Sussex, United Kingdom, PO19 6SE
Worthing Hospital
Worthing, West Sussex, United Kingdom, BN11 2DH
Pinderfields General Hospital
Wakefield, West Yorkshire, United Kingdom, WF1 4DG
Kidderminster Hospital
Kidderminster, Worcestershire, United Kingdom, DY11 6RJ
Alexandra Hospital
Redditch, Worcestershire, United Kingdom, B98 7UB
Worcester Royal Hospital
Worcester, Worcestershire, United Kingdom, WR5 1DD
St James's University Hospital
Leeds, Yorkshire, United Kingdom, LS9 7TF
University College Hospital
London, United Kingdom, NW1 2BU
Withington Hospital
Manchester, United Kingdom, M20 2LR
Wythenshawe Hospital
Manchester, United Kingdom, M23 9LT
Sponsors and Collaborators
Institute of Cancer Research, United Kingdom
National Institute for Health Research, United Kingdom
Investigators
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Principal Investigator: Hugh Mostafid Royal Surrey County Hospital NHS Foundation Trust

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Responsible Party: Institute of Cancer Research, United Kingdom
ClinicalTrials.gov Identifier: NCT02070120     History of Changes
Other Study ID Numbers: ICR-CTSU/2013/10041
2013-005095-18 ( EudraCT Number )
First Posted: February 25, 2014    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018

Keywords provided by Institute of Cancer Research, United Kingdom:
Nonmuscle invasive bladder cancer (NMIBC)
Mitomycin C
Chemoresection

Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors