Whole Brain Radiotherapy following local treatment of melanoma

ISRCTN	ISRCTN12545499
DOI	https://doi.org/10.1186/ISRCTN12545499
ClinicalTrials.gov number	NCT01503827
Secondary identifying numbers	9841

Submission date: 28/07/2011
Registration date: 28/07/2011
Last edited: 07/11/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-radiotherapy-melanoma-that-has-spread-brain

Study website

Contact information

Mrs Barbara Searle
Scientific

Department of Oncology
University of Oxford
Old Road Campus Research Building
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom

Study information

Study design	Randomised, interventional, treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Whole Brain Radiotherapy following local treatment of intracranial metastases of melanoma a randomised phase III trial
Study acronym	WBRT
Study objectives	Brain metastases are a common cause of death in patients with melanoma. The use of whole brain radiotherapy (WBRT) after excision and/or stereotactic irradiation for melanoma brain metastases is variable and controversial because there is no high quality evidence to guide practice. This study looks at whether the addition of WBRT following excision/steriotactic irradiation will improve intracranial control and survival, without significant impairment of quality of life or neurocognitive function. Participants are randomly assigned to have WBRT or not after treatment of their brain metastases. Randomisation should occur within 6 weeks of completion of local treatment. If allocated, WBRT treatment is given as 30 Gy in 10 fractions and should start within 8 weeks of local treatment. On 10/04/2014 the following changes were made to the trial record: 1. The anticipated end date was changed from 30/04/2014 to 30/04/2018 2. The target number of participants UK sample size was changed from 40 to 20
Ethics approval(s)	Oxfordshire Research Ethics Committee C, 14 March 2011, ref: 11/H0606/1
Health condition(s) or problem(s) studied	Melanoma
Intervention	1. Patients will be randomised 1:1 using an Interactive Voice Randomisation System (IVRS) 2. Randomisation will be stratified by centre, gender, number of CNS metastases, extracranial metastases and planned radiotherapy. 3. WBRT, 30 Gy in 10 fractions
Intervention type	Other
Primary outcome measure	The proportion of patients with distant intracranial failure at 12 months after follow-up
Secondary outcome measures	1. Deterioration in neurocognitive function (NCF) 2. The main neurocognitive function endpoint will be defined as the proportion of patients who have deterioration 3. Overall survival - will be assessed from date of randomisation to date of death from any cause 4. Time to deterioration in health related Quality of Life parameters - the primary QOL endpoint will be time to deterioration in role function from randomisation, with deterioration 5. Time to deterioration in performance status as measured by ECOG - defined as the time that elapses between randomisation and the first recorded worsening (including time to distant intracranial failure) measured by the time difference between the randomisation MRI and Intracranial Failure 6. Time to local intracranial failure measured by the time difference between the pre-randomisation MRI and Intracranial Fail 7. Time to overall (distant + local) intracranial failure, determined through MRI and is defined as the time to the first recurrence of disease anywhere Added 10/04/2014: 8. Incremental cost-effectiveness ratio (ICER). A within-trial economic evaluation of WBRT compared to observation
Overall study start date	01/05/2011
Completion date	30/04/2018

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 200; UK Sample Size: 20
Key inclusion criteria	Current inclusion criteria as of 10/04/2014: 1. One to three intracranial metastases on MRI from melanoma, locally treated with either surgical excision and/or stereotactic irradiation. It will be assumed that the metastases are melanoma if the patient has documented histological or radiological concurrent extracranial disease that has already made the patient stage IV. If the cerebral lesion(s) is/are the first presentation of stage IV disease, then one metastasis must be histologically proven to be melanoma for the patient to be included in the study 2. Life expectancy of at least 6 months 3. Aged 18 years or older 4. WBRT must begin within 8 weeks of completion of localised treatment and within 4 weeks of randomisation 5. Able to have an MRI brain scan with contrast. Estimated Glomerular Filtration Rate (eGFR) is adequate at the discretion of the radiologist and capable of having gadolinium-containing contrast medium for MRI (as per practice guidelines). 6. Localised treatment of all these metastases no more than 6 weeks prior to randomisation 7. An ECOG performance status between 0 and 2 at randomisation 8. CT or PET scan of chest, abdomen and pelvis as a minimum prior to randomisation. Scans must be within 12 weeks of randomisation 9. Serum Lactate Dehydrogenase (LDH) must be = 2 x upper limit of normal 10. Able to provide written informed consent 11. Male or female participants Previous inclusion criteria: 1. One to three intracranial metastases on MRI from melanoma, locally treated with either surgical excision and/or stereotactic irradiation. It will be assumed that the metastases are melanoma if the patient has documented histological or radiological concurrent extracranial disease that has already made the patient stage IV. If the cerebral lesion(s) is/are the first presentation of stage IV disease, then one metastasis must be histologically proven to be melanoma for the patient to be included in the study 2. Life expectancy of at least 6 months 3. Aged 18 years or older 4. WBRT must begin within 8 weeks of completion of localised treatment and within 4 weeks of randomisation 5. Able to have an MRI brain scan with contrast. Estimated Glomerular Filtration Rate (eGFR) is adequate at the discretion of the radiologist and capable of having gadolinium-containing contrast medium for MRI (as per practice guidelines). 6. Localised treatment of all these metastases no more than 6 weeks prior to randomisation 7. An ECOG performance status between 0 and 2 at randomisation 8. CT scan of chest, abdomen and pelvis as a minimum prior to randomisation. Scans must be within 12 weeks of randomisation 9. Serum Lactate Dehydrogenase (LDH) must be = 2 x upper limit of normal 10. Able to provide written informed consent 11. Male or female participants
Key exclusion criteria	1. Any untreated intracranial disease 2. Any previous intracranial treatment (surgical excision and/or stereotactic irradiation treatment and/or WBRT) prior to this diagnosis of intracranial melanoma 3. Evidence of leptomeningeal disease on pre-local treatment MRI scan 4. Patients with prior cancers, except: 4.1. Those diagnosed more than five years ago with no evidence of disease recurrence within this time 4.2. Successfully treated basal cell and squamous cell skin carcinoma 4.3. Carcinoma in-situ of the cervix 5. A medical or psychiatric condition that compromises ability to give informed consent or complete the protocol 6. Positive urine pregnancy test for women of childbearing potential (+/-7 days of registration onto the trial)
Date of first enrolment	01/05/2011
Date of final enrolment	30/04/2018

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Department of Oncology

Oxford
OX3 7DQ
United Kingdom

Sponsor information

University of Oxford (UK)
University/education

Joint Research Office
Block 60
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LE
England
United Kingdom

Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Charity

Cancer Research UK
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Other publications	interim analysis	08/05/2015	04/09/2019	Yes	No
Protocol article	protocol	17/04/2011	04/09/2019	Yes	No
Statistical Analysis Plan	statistical analysis plan	05/08/2019	04/09/2019	No	No
Results article		20/11/2019	07/11/2022	Yes	No

Editorial Notes

07/11/2022: Publication reference added.
04/09/2019: ClinicalTrials.gov number and publication references added.
22/05/2019: Internal review.