Whole Brain Radiotherapy Following Local Treatment of Intracranial Metastases of Melanoma

Study Overview
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Brief Summary
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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.

Official Title
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Whole Brain Radiotherapy Following Local Treatment of Intracranial Metastases of Melanoma - A Randomised Phase III Trial

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Radiation: WBRT


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WBRT<br>Patients will receive WBRT after local treatment. A minimum of 30 Gy in 10 fractions given as one fraction per day within 4 weeks of randomisation | Radiation: WBRT<br>* A minimum of 30 Gy in 10 fractions given as one fraction per day within 4 weeks of randomisation<br>|
| No Intervention: Observation<br>No Intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with distant intracranial failure as determined by magnetic resonance imaging (MRI) assessment |  | 12 months post randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to intracranial failure (local, distant and overall) as determined by MRI |  | Post randomisation to intracranial failure | 
| Quality of life as measured by EORTC QLQ-C30 and BN-20 |  | At baseline and every 2 months post randomisation | 
| 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). |  | At baseline and every 2 months post randomisation | 
| Overall survival |  | Post randomisation to death from any cause | 
| Performance status as measured by ECOG |  | At baseline and every 2 months post randomisation | 
| Incremental cost effectiveness ratio (ICER) |  | At 12 months from randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Whole Brain Radiotherapy, Brain metastases, Melanoma, Stage IV Metastatic Melanoma, Neurocognitive function, Quality of life