ideasIdea
Brain metastases included by default in every solid-tumour trial
Up to a fifth of people with advanced solid tumours have cancer in the brain and are usually barred from trials. Letting in those whose brain disease is treated, stable or symptom-free would widen trials and tell us whether drugs work in the brain.
Protocols would include patients with treated and stable brain metastases, and asymptomatic untreated metastases below a size threshold, with a pre-specified intracranial response assessment (RANO-BM) as a secondary endpoint. Exclusion would be allowed only for agents with a documented neurotoxicity signal or where the sponsor pre-registers a separate CNS cohort. The FDA brain metastases eligibility guidance supports this but uptake remains partial.
Hypothesis
Trials including stable and asymptomatic brain metastases will enrol faster, and the intracranial efficacy data generated will change labelling or guidelines for at least a quarter of new agents in lung, breast and melanoma within five years.
Rationale
Osimertinib, lorlatinib, tucatinib and trastuzumab deruxtecan changed practice for brain metastases only because trials permitted such patients. Excluding them creates an evidence vacuum for exactly the population with the greatest unmet need.
What would test it
Compare enrolment rate and CNS-relevant label changes between new registrational trials that adopt default inclusion versus those that do not, using ClinicalTrials.gov records over a three-year window.
Maturity
early clinical
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
- Trials enrol too few, too slowly · Fewer than one in ten adults with cancer joins a trial. Trials close for lack of patients, not lack of ideas.
- The brain: barrier and sanctuary · Most drugs cannot cross into the brain, so brain tumours and brain metastases lag every other site.