# Brain metastases included by default in every solid-tumour trial

Source: https://onco.cc/ideas/idea-tr1-brain-mets-default-included/  
OnCo record `idea-tr1-brain-mets-default-included` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed 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

## Sources

- FDA: Cancer Clinical Trial Eligibility Criteria: Brain Metastases: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-brain-metastases

## Connected records

- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [MRI](https://onco.cc/technologies/mri/)
- drugs: [Lorlatinib](https://onco.cc/drugs/lorlatinib/), [Osimertinib](https://onco.cc/drugs/osimertinib/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- bottlenecks: [The brain: barrier and sanctuary](https://onco.cc/bottlenecks/b-brain-delivery/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- ideas: [Measure brain metastasis prevention as a primary endpoint, not as a secondary one](https://onco.cc/ideas/idea-lung-brain-metastasis-prevention-as-a-primary-endpoint/)

---
JSON: https://onco.cc/api/v1/entities/idea-tr1-brain-mets-default-included.json