Study of Tumour Focused Radiotherapy for Bladder Cancer

Bladder Cancer Clinical Trial

— RAIDER  

Official title:

A Randomised Phase II Trial of Adaptive Image Guided Standard or Dose Escalated Tumour Boost Radiotherapy in the Treatment of Transitional Cell Carcinoma of the Bladder

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02447549
• Other study ID #: ICR-CTSU/2014/10049
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 21, 2015
• Est. completion date: March 2029

Study information

• Verified date: June 2020
• Source: Institute of Cancer Research, United Kingdom
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Bladder cancer is the seventh most common cancer in the UK, with 10,399 new cases diagnosed in 2011. In a quarter of these cases the cancer has infiltrated the muscular wall of the bladder (muscle invasive) and is life threatening. This type of bladder cancer is usually treated either with surgical removal of the bladder, or daily radiotherapy treatment (high strength xrays which kill cells), given every day for 4 or 7 weeks. RAIDER will investigate methods which have the potential to improve how well this radiotherapy works.

RAIDER is based on a study of novel radiotherapy techniques which was conducted at a single UK NHS Trust. Bladder radiotherapy is normally delivered using a single plan throughout treatment and treats the whole bladder with the same radiotherapy dose. In adaptive radiotherapy the delivery plan is chosen from 3 possible plans. In cancer (tumour) focused radiotherapy, the highest dose of the radiotherapy is aimed at the tumour within the bladder.

In RAIDER, at least 240 participants with muscle invasive bladder cancer will be in one of 3 treatment groups:

1. standard whole bladder radiotherapy

2. standard dose tumour focused adaptive radiotherapy

3. dose escalated tumour boost adaptive radiotherapy

Participants will visit the hospital 4 weeks, 3, 6, 9, 12, 18 and 24 months after radiotherapy and annually thereafter to check whether the cancer has returned and to receive treatment for any symptoms they may be experiencing.

RAIDER aims to confirm in a multicentre setting that novel techniques allow a higher radiotherapy dose than standard to be reliably targeted at the tumour within the bladder and to check that the long term side effects of the treatment are acceptable. If this is the case, results of RAIDER will be used to develop a study to establish whether dose escalated radiotherapy is better at treating bladder cancer than standard dose.

Description:

RAIDER has a two stage design. Stage 1 will establish the feasibility of delivering DART in a multi-centre setting, and stage 2 will establish the toxicity of DART. 72 patients will be recruited in stage 1, with at least an additional 168 patients in stage 2 (sufficient to recruit 57 evaluable participants to the DART group in each fractionation cohort).

Both fractionation regimens in standard use in UK are included - 32f and 20f. Participants will be permitted to receive concomitant chemotherapy. Primary endpoints will be assessed in each fractionation cohort separately with the flexibility to drop either a fractionation cohort or an experimental treatment group (on advice of Independent Data Monitoring Committee) following completion of stage 1.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 345
• Est. completion date: March 2029
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent

• Age =16 years

• Histologically or cytologically confirmed transitional cell carcinoma (TCC) of the bladder

• Unifocal bladder TCC staged T2-T4a N0 M0*

• Fit to receive a radical course of radiotherapy

• WHO performance status 0-2

• Willing and able to comply with study procedures and follow up schedule *Tumour location must be clearly visible on imagine or recorded on a surgical bladder map

Exclusion Criteria:

• Nodal or metastatic disease

• Multifocal invasive disease

• Simultaneous TCC in upper tract or urethra

• Pregnancy

• Active malignancy within 2 years of randomisation (not including non melanomatous skin carcinoma, previous non muscle invasive bladder tumours, NCCN low risk prostate cancer (T1/T2a, Gleason 6 PSA <10), in situ carcinoma of any site)

• Bilateral hip replacements

• Any other conditions that in the Principal Investigator's opinion would be a contra-indication to radiotherapy (e.g. previous pelvic radiotherapy / inflammatory bowel disease)

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Radiation:
• WBRT
One RT plan with whole bladder treated to standard dose.
• SART
Three plans (small, medium & large) generated with the standard dose of RT focused on the tumour, sparing the normal bladder from full dose radiation. Pretreatment cone beam CTs will be used to select the best fitting of the three plans prior to treatment.
• DART
Three plans (small, medium & large) generated with a higher dose than standard focused on the tumour and the remainder of the bladder treated to the same dose as in the SART group. Pretreatment cone beam CTs will be used to select the best fitting of the three plans prior to treatment.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Townsville General Hospital	Douglas	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Austin Hospital	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Radiation Oncology Mater Centre QLD	South Brisbane	Queensland
Australia	Riverina Cancer Care Centre	Wagga Wagga	New South Wales
New Zealand	Auckland Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Waikato	Hamilton
United Kingdom	Maidstone Hospital, Kent Oncology Centre	Adstone
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust	Birmingham
United Kingdom	Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust	Birmingham
United Kingdom	Bradford Teaching Hospitals NHS Foundation Trust	Bradford
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Bristol Haematology & Oncology Centre	Brixton
United Kingdom	West Suffolk Hospital	Bury St Edmunds
United Kingdom	Addenbrooke's Hospital	Cambridge
United Kingdom	Velindre Hospital, Cardiff and Vale NHS Trust	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Royal Devon and Exeter Hospital	Exeter
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	St Luke's Cancer Centre	Guildford
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Barts Health NHS Trust	London	England
United Kingdom	Guy's and St Thomas' Hospital	London
United Kingdom	Royal Marsden NHSFT	London
United Kingdom	Royal Oldham Hospital	Manchester
United Kingdom	The Christie NHS Foundation Trust	Manchester	England
United Kingdom	Northern Centre for Cancer Care, Freeman Hospital,	Newcastle upon Tyne
United Kingdom	Mount Vernon Cancer Centre	Northwood	Middlesex
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Nottingham University Hospital NHS Trust	Nottingham	England
United Kingdom	The Royal Oldham Hospital	Oldham
United Kingdom	Peterborough City Hospital	Peterborough
United Kingdom	Queen Alexandra Hospital	Portsmouth
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust	Romford	Essex
United Kingdom	Weston Park Hospital, Sheffield Teaching Hospitals Trust	Sheffield
United Kingdom	Kings Mill Hospital, Sherwood Forest Hospitals Foundation NHS Trust	Sutton-in-Ashfield
United Kingdom	Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust	Taunton
United Kingdom	Torbay District General Hospital	Torquay	Devon
United Kingdom	Mid Yorkshire Hospitals	Wakefield
United Kingdom	Pinderfields hospital, The Mid Yorkshire Hospitals NHS Trust	Wakefield
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral

Sponsors (2)

Lead Sponsor	Collaborator
Institute of Cancer Research, United Kingdom	Trans-Tasman Radiation Oncology Group (TROG)

Countries where clinical trial is conducted

Australia,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants meeting predefined radiotherapy dose constraints in DART group	Primary outcome of stage 1 of study, predefined radiotherapy dose constraints for bladder, bowel and rectum met for medium plan in DART group.	4-6 weeks from randomisation
Primary	Proportion of patients experiencing severe late side effects following radiotherapy.	Primary outcome of stage 2 of study, late CTC toxicity grade 3 or higher.	6-18 months post radiotherapy
Secondary	Clinician reported acute toxicity	CTCAE v4	0-6 months post radiotherapy
Secondary	Patient reported outcomes- symptomatic toxicity	Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire	0-24 months post radiotherapy
Secondary	Patient reported outcomes- urinary side effects	King's Health Questionnaire (KHQ)	0-24 months post radiotherapy
Secondary	Patient reported outcomes- sexual function	excerpt of the EORTC QLQ-BLM30 questionnaire	0-24 months post radiotherapy
Secondary	Patient reported outcomes- chronic gastrointestinal symptoms	Assessment of Late Effects of RadioTherapy - Bowel (ALERT-B) questionnaire	0-24 months post radiotherapy
Secondary	Patient reported outcomes- health status	EQ-5D questionnaire	0-24 months post radiotherapy
Secondary	Loco-regional MIBC control	Control of existing MIBC	0-5 years post radiotherapy
Secondary	Progression free survival	Freedom from progressive disease	0-5 years post radiotherapy
Secondary	Overall survival	Death from any cause	0-5 years post radiotherapy