Accrual to a randomised trial of adjuvant whole brain radiotherapy for treatment of melanoma brain metastases is feasible

Abstract

BackgroundBrain metastases (BMs) are common in melanoma patients. Adjuvant whole brain radiotherapy (WBRT) following local treatment of intracranial melanoma metastases with neurosurgery and/or stereotactic radiosurgery is controversial. A randomised trial is needed. However, accrual to WBRT trials has been problematic. A pilot study by Australia and New Zealand Melanoma Trials Group (ANZMTG) was conducted to see if accrual was feasible.MethodsSites canvassed for interest included those who treat melanoma patients, had a proven accrual in previous melanoma trials and who had the relevant infrastructure support. Feasibility forecasts from interested sites were sought. These were compared to the patient numbers documented in the research contracts. A target accrual of 60 patients in 2 years was set. Funding was sought for the pilot study. Basic demographics of the pilot study cohort were collected.ResultsThe first centre opened December 2008; the first patient was randomised in April 2009. The pilot accruing period concluded in September, 2011. In 30 months, 54 patients from 10 of a total of 17 activated sites in Australia (39, 72%) and in Norway (15, 28%) had been accrued. Feasibility forecasts predicted 133 trial eligible patients per year (including 108 Australian + 25 International patients). Site estimates generally overestimated accrual with 4 of 17 active sites estimating within 50% of target numbers. Sites with patient estimates calculated from records were more accurate than those estimated from memory. The overall recruitment target was lower in the research contracts when compared to the feasibility evaluation. Basic demographics of the pilot study revealed 62% of patients were males; 58% had a single metastasis, 28% had two and 14% had three metastases. 12-month overall survival was 50%.ConclusionsDespite only 54 patients and not the full 60 patient target being accrued in two years the Trial Management Committee and Data Safely Monitoring Committee approved the continuation of the pilot study to the main trial. On the basis of this successful pilot study, funding was achieved for the full study. 143 patients of a target of 200 have been randomised by June 2014.

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

“…A number of investigators noted that referring clinicians often have strong anecdotal preferences on whether or not to refer patients with brain metastases for WBRT, based on concerns over WBRT-related toxicities, and melanoma traditionally being viewed as a radio-resistant disease (Roos et al , 2006; Redmond et al , 2008; Fogarty et al , 2014). With this in mind, Fogarty et al undertook a wide consultation amongst clinicians treating melanoma when setting up their phase 3 trial of WBRT after local treatment of melanoma brain metastases (Fogarty et al , 2011).…”

“…Careful selection of study sites with proven ability to recruit within the desired patient population, possession of full on-site treatment facilities and multi-disciplinary clinics, is considered crucial for successful recruitment (Neuhaus et al , 2009; Langley et al , 2013; Fogarty et al , 2014). Central coordination of site set-up and ethics submissions have also been identified as important for successful study accrual (Fogarty et al , 2014).…”

“…Central coordination of site set-up and ethics submissions have also been identified as important for successful study accrual (Fogarty et al , 2014). …”

“…As part of their phase 3 trial of WBRT after local treatment of melanoma brain metastases, Fogarty et al (2014) undertook a pilot study to assess if accrual to the main study was feasible. Through this they identified that even study sites with proven track records for accrual to melanoma trials often overestimated how many patients they could recruit.…”

Clinical Management of Multiple Melanoma Brain Metastases

“…There have been no randomized studies of surgery in patients with MBM and as such, radiation therapy has been the standard treatment in the management of these patients. To date, there have been no reported RCTs of WBRT compared to SRS for patients with MBM from melanoma, although one study is currently enrolling patients 26 . There are, however, many RCTs of patients with brain metastases from mixed histologies which help provide insight into to the role of radiation therapy for MBM.…”