Whole Brain Radiotherapy following local treatment of intracranial metastases of melanoma – A randomised Phase III trial.
The study has received a favourable opinion from ethics.
To determine the effect of adding WBRT to local treatment on distant intracranial control (primary), quality of life (QoL), performance status, neurocognitive function (NCF) and overall survival.
Open to recruitment
Number of active sites: 9
Target recruitment: 200 (20 patients in the UK)
10 patients (Apr 2015)
- One to three (1-3) 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.
- 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 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).
- Localised treatment of all these metastases no more than 6 weeks prior to randomisation.
- An ECOG performance status between 0 and 2 at randomisation.
- CT or PET scan of chest, abdomen and pelvis as a minimum prior to randomisation. Scans must be within 8 weeks of randomisation.
- Serum Lactate Dehydrogenase (LDH) must be ≤ 2 x upper limit of normal.
- Able to provide written informed consent.
- 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: (a) those diagnosed more than five years ago with no evidence of disease recurrence within this time; (b) successfully treated basal cell and squamous cell skin carcinoma; (c) 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 (+-7 days of registration onto the trial).
To assess the effect of WBRT (after localised treatment for melanoma brain metastases) on distant intracranial control, as assessed by MRI scanning.
To assess the effect of WBRT (after localised treatment for melanoma brain metastases) on:
- Time to intracranial failure (local, distant and overall (local+ distant)) as assessed by MRI
- Quality of life
- Performance status
- Neurocognitive function
- Overall survival
- Death from neurological causes or not
- Cost-effectiveness of WBRT from the perspective of (a) the health system, and (b) patients incurring out-of-pocket costs.
Deterioration in neurocognitive function and distant intracranial failure will be assessed for the following subgroups:
- One vs more than one cerebral metastasis
- Presence of extracranial disease vs none
- 65 years of age vs. ≥over 65 years of age
- Patients treated with immune or targeted therapies vs. patients who did not receive treatment with immune or targeted therapies