CALIBER

• Research type

  Research Study

• Full title

  A phase II randomised feasibility study of chemoresection and surgical management in low risk non muscle invasive bladder cancer.

• IRAS ID

  135378

• Contact name

  Hugh Mostafid

• Contact email

  Hugh.mostafid@nhs.net

• Sponsor organisation

  The Institute of Cancer Research

• Eudract number

  2013-005095-18

• Clinicaltrials.gov Identifier

  NCT02070120

• Clinicaltrials.gov Identifier

  CCR4134, Committee for Clinical Research

• Research summary

  Research Summary

  CALIBER is investigating treatment of low risk non-muscle invasive bladder cancer (NMIBC). This is diagnosed in 5,000 people in the UK each year and frequently comes back following initial treatment (recurs), but rarely progresses to a life threatening condition. European guidelines on NMIBC treatment and monitoring recommend that patients treated for low risk NMIBC should have annual outpatient check-ups involving the introduction of a telescope into the bladder (cystoscopy) under local anaesthetic. Should a recurrence be found, an operation (usually under general anaesthetic) is scheduled to surgically remove the tumour.

  A 100 patient survey of those with low risk NMIBC indicated that inpatient surgery for recurrence was the most bothersome aspect of their condition. This led to the development of CALIBER to investigate using chemotherapy delivered into the bladder (chemoresection) as an outpatient alternative to surgery. Chemotherapy is routinely used following surgery to treat patients with higher risk NMIBC and may enable low risk patients to avoid surgery altogether.

  174 participants with recurrent low risk NMIBC will be invited to join CALIBER and will be randomly assigned between surgical management of recurrence and 4 outpatient treatments of chemoresection over 4 weeks.

  CALIBER aims to demonstrate that chemoresection offers 6 in 10 participants the opportunity to avoid surgery for their recurrent tumours at 3 months. This would provide support for further investigation into chemoresection as a treatment strategy for recurrent low risk NMIBC patients, with the aim of reducing the impact of treatment of recurrence on patients’ daily lives.

  This trial is investigator designed and led, has been approved by the Research for Patient Benefit funding stream of the National Institute for Health Research (NIHR) and will be conducted at NHS hospitals across the UK.

  Summary of Results

  Results of CALIBER: A phase II randomised feasibility study of Chemoresection and surgicAl management in Low rIsk non muscle invasive Bladder cancER

  CALIBER was a study in low risk bladder cancer which came back after previous treatment. This study aimed to find out whether using chemotherapy inside the bladder (chemoresection) might allow people to avoid surgery if their low risk bladder cancer came back (recurred) after being treated. To measure how well chemoresection worked we looked at whether there was any cancer left in the bladder three months after treatment.
  
  In August 2017 a group of independent experts reviewed all available data collected. They advised that enough information was available to determine the results of the study and that no further participants were required. We stopped inviting new people to join CALIBER in September 2017. In total 82 people joined the study.

  Background
  Participants in CALIBER joined one of the following treatment groups:
  • Group 1: Surgical management – people in this group received the surgery they would have had if they had not joined the study.
  • Group 2: Chemoresection – people in this group had mitomycin C chemotherapy in their bladder once a week for 4 weeks and did not have surgery.

  Trial participation
  82 people joined CALIBER between January 2015 and September 2017
  • 28 people were in the surgical management group
  • 54 people were in the chemoresection group

  Patients from 24 NHS hospitals across the UK joined the study.

  How well did chemoresection work?
  We found that three months after treatment:
  • Eight out of ten people who had surgical management had no cancer in their bladder
  • Four out of ten people who had chemoresection had no cancer in their bladder
  This meant that chemoresection using mitomycin C did not work for as many people as we had hoped. Everyone who still had bladder cancer at this check up had surgery to treat it.

  Did the treatments have side effects?
  Very few side effects were reported. The most common side effect was needing to urinate more often than normal. Eight out of 28 people in the surgical management group and nine out of 53 people in the chemoresection group reported this side effect. No one in the study had severe side effects as a result of their treatment.

  Participants in both groups reported similar experiences of quality of life and general wellbeing in the questionnaires they completed.

  What do these results mean?
  These results show that chemoresection using mitomycin C is a safe treatment with few side effects and does help some people avoid surgery. However it does not treat low risk bladder cancer as well as we had hoped. Further research is required to determine whether using higher doses or different types of chemotherapy in the bladder might work better.

  This is an important scientific finding. Although the study has not led directly to a new treatment that is better than the current surgical treatment, this was not known before.

  What will happen now?
  Participants in the study donated a small sample of tissue left over from their bladder cancer surgery for laboratory research. This tissue will be available for future analyses to help us understand how best to treat bladder cancer in the future.

  Publication in BJU International
  The results of CALIBER were published in the British Journal of Urology (BJU) International medical journal.

• REC name

  South Central - Hampshire B Research Ethics Committee

• REC reference

  14/SC/1223

• Date of REC Opinion

  29 Aug 2014

• REC opinion

  Favourable Opinion