{"entity":{"id":"idea-tr1-brain-mets-default-included","kind":"idea","name":"Brain metastases included by default in every solid-tumour trial","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-08","links":[{"label":"FDA: Cancer Clinical Trial Eligibility Criteria: Brain Metastases","url":"https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-brain-metastases"}],"tags":[],"related":[],"cancers":["nsclc","breast-her2-positive","melanoma"],"sections":[],"technologies":["mri"],"targets":[],"drugs":["osimertinib","lorlatinib","tucatinib","trastuzumab-deruxtecan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-trial-enrolment","b-brain-delivery"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","test":"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","actor":"regulator","cost":"small","horizonYears":2},"route":"/ideas/idea-tr1-brain-mets-default-included/","neighbours":{"cancer":[{"id":"breast-her2-positive","kind":"cancer","name":"HER2-positive breast cancer","route":"/cancers/breast-her2-positive/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"mri","kind":"technology","name":"MRI","route":"/technologies/mri/"}],"drug":[{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"bottleneck":[{"id":"b-brain-delivery","kind":"bottleneck","name":"The brain: barrier and sanctuary","route":"/bottlenecks/b-brain-delivery/"},{"id":"b-trial-enrolment","kind":"bottleneck","name":"Trials enrol too few, too slowly","route":"/bottlenecks/b-trial-enrolment/"}],"idea":[{"id":"idea-lung-brain-metastasis-prevention-as-a-primary-endpoint","kind":"idea","name":"Measure brain metastasis prevention as a primary endpoint, not as a secondary one","route":"/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/"}]}}