Clinical trial NCT02447549: Study of Tumour Focused Radiotherapy for Bladder Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Bladder Cancer
Keywords: IMRT
IGRT
Muscle invasive
Adaptive Radiotherapy
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Trans Tasman Radiation Oncology Group
First posted: 2015-05-19
Enrollment: 345
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of participants meeting predefined radiotherapy dose constraints in DART group
timeFrame: 4-6 weeks from randomisation
measure: Proportion of patients experiencing severe late side effects following radiotherapy.
timeFrame: 6-18 months post radiotherapy
Secondary outcomes:
measure: Clinician reported acute toxicity
timeFrame: 0-6 months post radiotherapy
measure: Patient reported outcomes- symptomatic toxicity
timeFrame: 0-24 months post radiotherapy
measure: Patient reported outcomes- urinary side effects
timeFrame: 0-24 months post radiotherapy
measure: Patient reported outcomes- sexual function
timeFrame: 0-24 months post radiotherapy
measure: Patient reported outcomes- chronic gastrointestinal symptoms
timeFrame: 0-24 months post radiotherapy
measure: Patient reported outcomes- health status
timeFrame: 0-24 months post radiotherapy
measure: Loco-regional MIBC control
timeFrame: 0-5 years post radiotherapy
measure: Progression free survival
timeFrame: 0-5 years post radiotherapy
measure: Overall survival
timeFrame: 0-5 years post radiotherapy
Other outcomes:
Locations:
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
state: New South Wales
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Douglas
country: Australia
facility: Townsville General Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Radiation Oncology Mater Centre QLD
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hamilton
country: New Zealand
facility: Waikato
city: Torquay
country: United Kingdom
facility: Torbay District General Hospital
state: Devon
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
state: England
city: Romford
country: United Kingdom
facility: Queen's Hospital, Barking Havering and Redbridge University Hospitals NHS Trust
state: Essex
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Middlesex
city: Ayr
country: United Kingdom
facility: Ayr Hospital
state: Scotland
city: Adstone
country: United Kingdom
facility: Maidstone Hospital, Kent Oncology Centre
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Trust
city: Bradford
country: United Kingdom
facility: Bradford Teaching Hospitals NHS Foundation Trust
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Brixton
country: United Kingdom
facility: Bristol Haematology & Oncology Centre
city: Bury St Edmunds
country: United Kingdom
facility: West Suffolk Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Hospital, Cardiff and Vale NHS Trust
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Guildford
country: United Kingdom
facility: St Luke's Cancer Centre
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: Royal Marsden NHSFT
city: Manchester
country: United Kingdom
facility: Royal Oldham Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Northern Centre for Cancer Care, Freeman Hospital,
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Oldham
country: United Kingdom
facility: The Royal Oldham Hospital
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
city: Preston
country: United Kingdom
facility: Royal Preston Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital, Sheffield Teaching Hospitals Trust
city: Sutton-in-Ashfield
country: United Kingdom
facility: Kings Mill Hospital, Sherwood Forest Hospitals Foundation NHS Trust
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital, Taunton and Somerset NHS Foundation Trust
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire Hospitals
city: Wakefield
country: United Kingdom
facility: Pinderfields hospital, The Mid Yorkshire Hospitals NHS Trust
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: Institute of Cancer Research/RMNHSFT
name: Robert Huddart
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hafeez S, Lewis R, Hall E, Huddart R; RAIDER Trial Management Group. Advancing Radiotherapy for Bladder Cancer: Randomised Phase II Trial of Adaptive Image-guided Standard or Dose-escalated Tumour Boost Radiotherapy (RAIDER). Clin Oncol (R Coll Radiol). 2021 Jun;33(6):e251-e256. doi: 10.1016/j.clon.2021.02.012. Epub 2021 Mar 23. No abstract available.
citation: Hafeez S, Webster A, Hansen VN, McNair HA, Warren-Oseni K, Patel E, Choudhury A, Creswell J, Foroudi F, Henry A, Kron T, McLaren DB, Mitra AV, Mostafid H, Saunders D, Miles E, Griffin C, Lewis R, Hall E, Huddart R. Protocol for tumour-focused dose-escalated adaptive radiotherapy for the radical treatment of bladder cancer in a multicentre phase II randomised controlled trial (RAIDER): radiotherapy planning and delivery guidance. BMJ Open. 2020 Dec 31;10(12):e041005. doi: 10.1136/bmjopen-2020-041005.
citation: Hafeez S, Lewis R, Griffin C, Hall E, Huddart R. Failing to Close the Gap Between Evidence and Clinical Practice in Radical Bladder Cancer Radiotherapy. Clin Oncol (R Coll Radiol). 2021 Jan;33(1):46-49. doi: 10.1016/j.clon.2020.07.001. Epub 2020 Aug 3. No abstract available.