Condition category
Cancer
Date applied
28/07/2011
Date assigned
28/07/2011
Last edited
14/07/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Mrs Barbara Searle

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

9841

Study information

Scientific title

Whole Brain Radiotherapy following local treatment of intracranial metastases of melanoma a randomised phase III trial

Acronym

WBRT

Study hypothesis

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

Oxfordshire Research Ethics Committee C, 14 March 2011, ref: 11/H0606/1

Study design

Randomised, interventional, treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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

Phase

Phase III

Drug names

Primary outcome measures

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 trial start date

01/05/2011

Overall trial end date

30/04/2018

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 200; UK Sample Size: 20

Participant 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)

Recruitment start date

01/05/2011

Recruitment end date

30/04/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Oncology
Oxford
OX3 7DQ
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

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

Sponsor type

University/education

Website

http://www.ox.ac.uk/

Funders

Funder type

Charity

Funder name

Cancer Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes