Patients with brain metastases are an underserved population
Brain metastases occur in 20-40% of all patients with cancer. Brain metastases are particularly common following lung and breast cancers, but treatments are limited and prognosis poor.
One of the challenges in treating brain metastases is the inability of many drugs to penetrate the blood-brain barrier into tumour tissue. Researchers hypothesised that radiotherapy could disrupt the blood-brain barrier and allow drugs to pass through and reach the tumour.
CamBMT1: Could radiotherapy improve treatments?
The current treatment for a patient diagnosed with a large metastatic brain tumour arising from primary lung or breast cancer would be surgery. In the CamBMT1 study, researchers are using the time between the patient’s diagnosis and surgery to administer a non-small cell lung cancer drug, afatinib. Patients are randomised to receive the drug with or without a dose of radiotherapy. When the patient undergoes surgery, the researchers measure the concentration of drug which has penetrated into the resected tumour.
The phase 1b part of the CamBMT1 trial was undertaken at Cambridge University Hospitals where a total of 10 patients were treated. Initial results, presented as an oral presentation at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting, and which will shortly be submitted for publication, show that the technique was feasible in patients with operable brain metastasis and that afatinib was shown to reach the tumour. The randomised phase 2 part of the trial is testing directly whether radiotherapy facilitates better drug delivery to the tumour, comparing the delivery of afatinib in combination with two different doses of radiotherapy and no radiotherapy at all. Multiple UK centres are seeking to recruit a total of 21 patients by the end of 2020.
Table 1: UK centres currently recruiting patients to CamBMT1
|Cambridge University Hospitals NHS Foundation Trust
|University Hospitals Birmingham NHS Foundation Trust
|The Beatson West of Scotland Cancer Centre
|Clatterbridge Cancer Centre / The Walton Centre
|The Christie NHS Foundation Trust
|Oxford University Hospitals NHS Foundation Trust
* Phase 2 recruitment is currently paused during the COVID-19 outbreak
NCRI Groups supporting CamBMT1
During the development the trial design was presented to various NCRI Groups including the Lung Group, Breast Group and Brain Group who provided feedback and support for the trial. NCRI’s Clinical and Translational Radiotherapy Research Group (CTRad) also provided suggestions to the researchers. CTRad members suggested adding a third treatment arm to the trial, administering either a low or high dose of radiotherapy. This would allow the researchers to measure if the effect of the radiotherapy was dose-dependent and also determine the best dose of radiotherapy to support drug delivery.
We received some helpful feedback on the study which resulted in key improvements being made to the study design.
Richard Baird, MD PhD, Principal Investigator, Cambridge University Hospitals NHS Foundation Trust and member of the Meningioma, Metastases & Other Tumours Subgroup.
CTRad was set up in 2009 to support the complex and challenging area of radiotherapy research in the UK. It brings together experts from different disciplines of radiation-related research
Impact past the initial patient population
The CamBMT1 trial is investigating the delivery of drugs to operable metastatic brain tumours. However, if radiotherapy does prove effective at disrupting the blood-brain barrier, it might provide an effective, safe and important strategy to improve treatment for patients with cancer that has spread to the brain, including brain tumours that are inoperable.