Clinical trial NCT01503827: Whole Brain Radiotherapy Following Local Treatment of Intracranial Metastases of Melanoma
Official title: Whole Brain Radiotherapy Following Local Treatment of Intracranial Metastases of Melanoma - A Randomised Phase III Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Metastatic Melanoma
Keywords: Whole Brain Radiotherapy
Brain metastases
Melanoma
Stage IV Metastatic Melanoma
Neurocognitive function
Quality of life
Lead sponsor: Melanoma and Skin Cancer Trials Limited
Sponsor class: OTHER
Collaborators: name: Trans Tasman Radiation Oncology Group
name: University of Oxford
First posted: 2012-01-04
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: People with brain metastases from melanoma are offered different treatment options after local treatment of their brain metastases via surgery or stereotactic irradiation. Depending on the treating institution and the clinician involved a patient may or may not be offered whole brain radiotherapy (WBRT) after their brain metastases are excised or treated with stereotactic irradiation. This trial seeks to determine if WBRT reduces the spread of brain metastases and lengthens the time to recurrence. The trial also examines the effect of WBRT on quality of life and brain functions such as memory, speech and concentration. Participants will be randomised after local treatment of their brain metastases to either WBRT or observation. 220 people will be recruited from sites in Australia, Norway, the UK, the US and other international sites.


Eligibility criteria: Inclusion Criteria:

* 1-3 intracranial metastases on MRI from melanoma, locally treated with either surgical excision and/or stereotactic irradiation.
* Life expectancy of at least 6 months
* Aged 18 years or older
* WBRT must begin within 8 weeks of completion of localised treatment and within 4 weeks of randomisation
* Able to have an MRI brain scan with contrast. Estimated Glomerular Filtrate Rate (eGFR) is adequate at the discretion of the radiologist and capable of having gadolinium-containing contrast medium for MRI as per practice guidelines
* Complete localised treatment of all these metastases no more than 6 weeks prior to randomisation
* An Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less at randomisation
* CT scan of chest, abdomen and pelvis as a minimum prior to randomisation. Scans must be within 12 weeks of randomisation
* Serum Lactate Dehydrogenase (LDH) must be = or \< 2 x upper limit of normal
* Able to provide written informed consent

Exclusion Criteria:

* Any untreated intracranial disease
* Any previous intracranial treatment (surgical excision and/or stereotactic irradiation treatment and/or WBRT) prior to this diagnosis of intracranial melanoma
* Evidence of leptomeningeal disease on pre-local treatment MRI scan
* Patients with prior cancers, except:

  * Those diagnosed more than five years ago with no evidence of disease recurrence within this time;
  * Successfully treated basal cell and squamous cell skin carcinoma;
  * Carcinoma in-situ of the cervix
* A medical or psychiatric condition that compromises ability to give informed consent or complete the protocol
* Positive urine pregnancy test for women of childbearing potential within a week of registration onto the trial

Primary outcomes:
measure: Proportion of patients with distant intracranial failure as determined by magnetic resonance imaging (MRI) assessment
timeFrame: 12 months post randomisation
Secondary outcomes:
measure: Time to intracranial failure (local, distant and overall) as determined by MRI
timeFrame: Post randomisation to intracranial failure
measure: Quality of life as measured by EORTC QLQ-C30 and BN-20
timeFrame: At baseline and every 2 months post randomisation
measure: Neurocognitive function as measured by Hopkins Verbal Learning Test, Controlled Oral Word Association Test, Trail Making Test Part A & B, Stroop - Colour and Word Test and Digit Span (Forwards and Backwards).
timeFrame: At baseline and every 2 months post randomisation
measure: Overall survival
timeFrame: Post randomisation to death from any cause
measure: Performance status as measured by ECOG
timeFrame: At baseline and every 2 months post randomisation
measure: Incremental cost effectiveness ratio (ICER)
timeFrame: At 12 months from randomisation
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Calvary Mater Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Genesis Cancer Care - Gateshead
state: New South Wales
city: North Sydney
country: Australia
facility: Melanoma Institute Australia / Royal Prince Alfred Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Darwin
country: Australia
facility: Darwin Hospital, NT Radiation Oncology
state: Northern Territory
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Radiation Oncology Services - Mater Centre
state: Queensland
city: Townsville
country: Australia
facility: Townsville Hospital
state: Queensland
city: Tugun
country: Australia
facility: Genesis Cancer Care - Tugun
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Oslo
country: Norway
facility: The Norwegian Radium Hospital
city: Whitchurch
country: United Kingdom
facility: Velindre Hospital
state: Cardiff
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Middlesex
city: Headington
country: United Kingdom
facility: Churchill Hospital
state: Oxford
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospital
Study officials:
affiliation: Mater Hospital, St Vincent's Hospital, Melanoma Institue Australia
name: Gerald Fogarty, BSc, MBBS
role: STUDY_CHAIR
References:
citation: Fogarty G, Morton RL, Vardy J, Nowak AK, Mandel C, Forder PM, Hong A, Hruby G, Burmeister B, Shivalingam B, Dhillon H, Thompson JF. Whole brain radiotherapy after local treatment of brain metastases in melanoma patients--a randomised phase III trial. BMC Cancer. 2011 Apr 17;11:142. doi: 10.1186/1471-2407-11-142.
citation: Hong AM, Fogarty GB, Dolven-Jacobsen K, Burmeister BH, Lo SN, Haydu LE, Vardy JL, Nowak AK, Dhillon HM, Ahmed T, Shivalingam B, Long GV, Menzies AM, Hruby G, Drummond KJ, Mandel C, Middleton MR, Reisse CH, Paton EJ, Steel V, Williams NC, Scolyer RA, Morton RL, Thompson JF. Adjuvant Whole-Brain Radiation Therapy Compared With Observation After Local Treatment of Melanoma Brain Metastases: A Multicenter, Randomized Phase III Trial. J Clin Oncol. 2019 Nov 20;37(33):3132-3141. doi: 10.1200/JCO.19.01414. Epub 2019 Sep 25.
citation: Lo SN, Hong AM, Haydu LE, Ahmed T, Paton EJ, Steel V, Hruby G, Tran A, Morton RL, Nowak AK, Vardy JL, Drummond KJ, Dhillon HM, Mandel C, Scolyer RA, Middleton MR, Burmeister BH, Thompson JF, Fogarty GB. Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan. Trials. 2019 Aug 5;20(1):477. doi: 10.1186/s13063-019-3555-5.